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1
Hawn, Sage E. "EXAMINATION OF BASAL NEUROENDOCRINE LEVELS IN OIF/OEF/OND VETERANS." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4206.
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Abstract
EXAMINATION OF BASAL NEUROENDOCRINE LEVELS IN OIF/OEF/OND VETERANS
By Sage E. Hawn, B.S.
A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.
Virginia Commonwealth University, 2015.
Major Director: Ananda B. Amstadter, PhD.
Associate Professor
Departments of Psychiatry, Psychology, & Human and Molecular Genetics
High rates of combat exposure exist among veterans of the recent conflicts, and are associated with debilitating mental health conditions, including posttraumatic stress disorder (PTSD). Numerous psychosocial and biologic factors are associated with PTSD, including the HPA-axis. The present study aimed to compare baseline neuroendocrine levels by trauma group (PTSD, trauma exposed [TE], and non-trauma controls [NTC]) among a sample of young veterans. An exploratory aim was to examine potential moderators of the relation between PTSD and basal cortisol/ACTH. Group differences in cortisol were nominally significant, with the NTC group having significantly higher cortisol than the PTSD group. Sleep disturbance was the only moderator of this relationship in cortisol, although lifetime trauma load significantly predicted basal cortisol across all models. No significant effects were demonstrated for ACTH. Examining effects of trauma on basal physiology provides a critical stepping ground for future investigations that may inform targeted prevention and intervention efforts.
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Saelzler, Ursula. "The relationship between basal cortisol levels and cognitive functioning across the adult lifespan." Thesis, Georgia Institute of Technology, 2016. http://hdl.handle.net/1853/55064.
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Age-related declines in cognitive functioning have been well documented, however, there are vast individual differences in the age of onset and magnitude of these changes. This observation has spurred the investigation of the potential risk factors for cognitive decline. Chronic elevations of the steroid hormone cortisol have been shown to compromise hippocampal- and frontal cortex- dependent cognitive tasks in rodents, non-human primates and Cushing’s disease patients. Several studies have extended these findings to investigate possible associations between cortisol and cognition in aging human populations. However, these previous examinations of the role of cortisol in cognitive aging have been hampered by the predominant use of single time-point measures of cortisol, small sample sizes, limited age ranges and/or constrained cognitive testing batteries. The present cross-sectional study investigated the relationship between basal cortisol levels, indexed by a 24-hr free cortisol to creatinine ratio, and cognitive functioning on twelve cognitive outcomes in a sample of 1,853 non-demented adults aged 18 to 93 years. The results showed that elevated cortisol levels had small but significant negative effects on verbal learning and working memory performance across the lifespan and significant negative effects limited to older age on a measure of speeded processing. Longitudinal investigation is warranted to examine if within-person changes in cortisol level predict cognitive change.
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Lai, Wai Bun Benjamin. "Basal and stress-reactive cortisol levels in patients with Inflammatory Bowel Diseases." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111935.
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Inflammatory Bowel Diseases (IBD) are chronic remitting-relapsing diseases of the gastrointestinal tract. Psychological stress has long been suspected to play a role in the pathogenesis and symptom exacerbation of IBD. The goal of this study was to examine whether or not there exist any differences in the stress reactivity in patients with IBD when compared to healthy controls. Salivary cortisol was employed as a biomarker to assess the activity of the hypothalamic-pituitary-adrenal (HPA) axis---normally activated upon the perception of a psychological stressor---in IBD patients and healthy controls. Ten quiescent IBD patients were recruited and each was asked to identify a healthy age- and gender-matched friend to participate in the study to act as a control. In addition, 10 healthy age- and gender-matched subjects who were not friends of the IBD patients were recruited as a second control group. All subjects completed 4 psychological questionnaires: the NEO Personality Five Factor Inventory; the Rosenberg Self-Esteem Scale; the Perceived Stress Scale; and the Coping Inventory for Stress Situations. Subjects were asked to sample their saliva at home in order to discern their basal salivary cortisol secretion pattern. As well, subjects underwent a psychosocial stress protocol, the Trier Social Stress Test (TSST), during which saliva samples were obtained to determine their stress-reactive cortisol levels. Results from this study indicate that IBD patients and their friends are significantly more agreeable in personality and showed a blunted HPA response to the TSST, when compared to healthy non-friends. These results point to a distinct personality profile and a possible social support phenomenon among IBD patients and their friends, which may modulate HPA reactivity to psychological stress and contribute to the differential cortisol response observed.
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Dinis, Marta Correia. "Utilidade do doseamento de cortisol basal no rastreio de hipoadrenocorticismo no cão : estudo retrospetivo." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2021. http://hdl.handle.net/10400.5/21465.
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Dissertação de Mestrado Integrado em Medicina VeterináriaRESUMO - O doseamento do cortisol basal tem sido utilizado na prática clínica para excluir hipoadrenocorticismo. Quando a sua concentração é superior a 2 g/dl, esta doença é excluída. Quando é inferior, é essencial realizar um teste de estimulação com a hormona adrenocorticotrófica (ACTH) para avaliar a função adrenal. O objetivo principal deste estudo foi explorar potenciais parâmetros clínicos que permitam auxiliar a avaliação da probabilidade de um cão com hipocortisolémia apresentar um teste de estimulação com ACTH normal. Foi conduzido um estudo restrospetivo caso-controlo utilizando os dados clínicos dos cães submetidos ao doseamento de cortisol basal no Hospital Escolar Veterinário durante 30 meses. Os cães foram incluídos se apresentassem uma hipocortisolémia basal (≤2 g/dl), e após este resultado, tenha sido efectuado um teste de estimulação com ACTH. Os dados colhidos incluíram sexo, idade, raça, sinais clínicos, análise hematológica e bioquímicas (incluindo eletrólitos), resultados dos testes funcionais e alterações ecográficas. De acordo com o resultado do teste de estimulação, os cães foram divididos em dois grupos: os cães com concentrações de cortisol após estimulação ≤2g/dl foram incluídos no grupo com hipoadrenocorticismo (HAC) e cães com valores superiores foram incluídos no grupo sem hipoadrenocorticismo (N-HAC). As variáveis foram comparadas entre grupos através de testes não paramétricos (teste exato de Fisher) e testes paramétricos (teste t para amostras independentes). 35 cães foram incluídos e divididos nos grupos de estudo: 9/35 no grupo HAC e 26/35 no grupo N-HAC. Ambos os grupos apresentavam sinais gastrointestinais crónicos (66.7% no grupo HAC e 50% no grupo N-HAC). Foi observada uma concentração de cortisol basal <1g/dl em 77.8% dos cães com HAC e em 30.7% dos cães N-HAC (p=0.01; rácio de probabilidade (OR) =7.38). A presença de poliúria/polidipsia (pu/pd), relatada pelos detentores, foi mais prevalente em cães com HAC (55.6%) face aos cães N-HAC (7.7%) (p=0.01; OR=15), bem como sinais de melena/hematoquézia (55.6%-grupo HAC; 0%-grupo N-HAC) (p=4x10-4; OR=64.8). Nas alterações laboratoriais, apenas o aumento da concentração de ureia revelou uma diferença significativa entre grupos (55.6%-grupo HAC; 11.6%-grupo N-HAC) (p=0.03; OR=7.9). Em suma, cães com hipocortisolémia basal, sem aumento dos níveis de ureia, pu/pd, e sem sinais de hemorragia gastrointestinal têm maior probabilidade de ter um teste de estimulação com ACTH normal. São necessários mais estudos para estender estas conclusões a um maior número de animais e para explorar o significado da hipocortisolémia em cães com o teste de estimulação com ACTH normal.
ABSTRACT - Use of basal cortisol concentrations measurement as a screening test for hypoadrenocorticism in dogs: a retrospective study - Basal cortisol measurement has been used on clinical practice to rule out hypoadrenocorticism. When its concentration is above 2g/dL, this disease is excluded. When it is lower, it is essencial to perform a adrenocorticotrophic hormone (ACTH) stimulation test to assess adrenal function. The main goal of this study is to explore potencional clinical parameters that can aid evaluating the odds of a dog with hypocortisolemia to have normal ACTH stimulation test response. A retrospective case-control study was conducted using the clinical data of all dogs submited to the measurement of basal cortisol at a Veterinary Teaching Hospital during 30 months. Dogs were included if presented basal hypocortisolemia (≤2 g/dl) and after that result, an ACTH stimulation test was executed. Collected data included sex, age, race, clinical signs, hematological and biochemical (including electrolytes) analysis, fuctional tests results and ecographic changes. Dogs were divided in two groups, according to the ACTH stimulation test result: dogs with pos-stimulation cortisol concentrations ≤2g/dl were included on the hypoadrenocorticism (HAC) group and dogs with higher values were included on the non-hypoadrenocorticism (N-HAC) group. Variables were compared between groups using non parametric tests (Fisher’s exact test) and parametric tests (independent sample t test). 35 dogs were included and distributed on the study groups: 9/35 (25.7%) on the HAC group and 26/35 (74.3%) on the N-HAC group. Both groups showed chronic gastrointestinal signs (66.7% on the HAC group and 50% on the N-HAC group). It’s was observed a basal cortisol concentration <1g/dl in 77.8% of dogs with HAC and in 30.7% of dogs with N-HAC (p=0.01; odds ratio (OR)=7.38). Polyuria/polydipsia (pu/pd) was more related by the detentor of the HAC dogs (55.6%) than by the N-HAC dogs (7.7%) (p=0.01; OR=15), as well as signs of melena/hematochezia (55.6%-HAC group; 0%-N-HAC group) (p=4x10-4; OR=64.8). About the laboratory changes, only higher values of urea concentration showed a significant difference between groups (55.6%-HAC group; 11.6%-N-HAC group) (p=0.03; OR=7.9). In summary, dogs with basal hypocortisolemia, without high urea levels, pu/pd, and gastrointestinal hemorrhage signs have higher chances to have a normal ACTH stimulation test. Further studies are needed, to extend these conclusions to a larger number of animals and to explore the relevance of hypocortisolemia in dogs with normal ACTH stimulation test.
N/A
5
Mendonça-Furtado, Olívia de. "Medidas de metabólitos de cortisol em macacos-prego (Gênero Sapajus): análise comparativa entre populações para investigação de fatores estressores." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/47/47132/tde-03122012-102144/.
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Estudos da fisiologia do estresse são de fundamental importância para a área de endocrinologia comportamental e para projetos visando à promoção do bem estar de animais cativos. Esses estudos, quando feitos com animais de vida-livre, possibilitam investigar quais estímulos ambientais ou sociais são estressores para o táxon estudado. Pouco se sabe a este respeito sobre macacos-prego (gênero Sapajus), um primata neotropical muito comum em zoológicos, criadouros e outras situações de cativeiro. Uma maior compreensão dos agentes estressores neste gênero pode contribuir para o bem estar de sujeitos cativos. Frente a isso, este trabalho objetivou: 1) investigar, a partir da variação dos níveis de glicocorticóides (GCs; hormônios ligados ao estresse), quais eventos ambientais e comportamentais são percebidos por macacos-prego selvagens como estressantes; 2) verificar a possibilidade de definir valores de referência de níveis aceitáveis (nível basal) de metabólitos fecais de glicocorticóides (MFGs a mensuração de GCs a partir de fezes permite avaliar estes hormônios de forma não-invasiva) para o gênero Sapajus; e 3) validar o protocolo experimental de extração e dosagem de hormônios fecais. Em relação aos dois primeiros objetivos, foram tomadas medidas de metabólitos fecais de glicocorticóides, e de dados ambientais e comportamentais de duas populações selvagens, uma do Parque Estadual Carlos Botelho/São Paulo (PECB) e outra da Fazenda Boa Vista/Piauí (FBV). Para a validação do protocolo experimental, foi realizado um desafio de ACTH e dexametasona com macacos-prego cativos. Análises por modelo linear generalizado misto (MLGM) mostraram diferença significativa entre os níveis basais de MFGs das duas populações estudadas, sendo maiores na população da FBV. Para esta população, foi encontrado efeito de oferta de frutos no habitat, de freqüência de encontros com outras espécies animais e de cópulas, sobre a variação mensal dos níveis basais de MFGs. Para a população do PECB, nenhuma das variáveis estudadas apresentou efeito significativo sobre a variação mensal dos níveis basais de MFGs. Já as análises individuais mostraram que interações agonísticas entre membros do grupo foram os maiores causadores de picos de MFGs nos sujeitos estudados, seguidos por fêmeas em período proceptivo e cópulas, que causaram picos não só em machos adultos, mas também em machos juvenis e nas próprias fêmeas. Os resultados do desafio de ACTH e de dexametasona validaram o protocolo experimental de extração e dosagem hormonal. Os resultados obtidos estão de acordo com pesquisas anteriores que revelaram diferenças marcantes no sistema social das duas populações, especialmente no que se refere às relações sociais de fêmeas, de acordo com as diferenças ecológicas entre as duas áreas. Além disso, sugerem que não é possível definir valores de referência de nível basal de MFGs para o gênero Sapajus, já que as duas populações diferem significativamente quanto a este aspecto. A partir deste trabalho, que é apenas o começo de uma longa jornada para a compreensão do estresse em macacos-prego selvagens, começa-se a entender quais são os estressores naturais destes animais e como eles impactam os níveis de MFGsStress physiology studies are of fundamental importance for the area of behavioral endocrinology and for projects that aim to promote the wellbeing of captive animals. When the subjects of those researches are wild animals, it is possible to investigate which environmental or social stimuli constitute stressors for this taxon. Little is known in this regard about capuchin monkeys (Sapajus genus), a neotropical primate that are constantly kept in zoos, breeders and others captive environments. A better comprehension of the stressors agents in this genus can contribute for the wellbeing of those captive individuals. Therefore this study aimed: 1) to investigate through the variation of glucocorticoids levels (GCs hormones related to stress), which environmental and behavioral events are perceived by wild capuchin monkeys as stressful; 2) access the possibility of defining basal fecal glucocorticoids metabolites levels (MFGs measuring GCs in feces is a non-invasive form of evaluate those hormones), as reference values, for the Sapajus genus; and 3) validate the experimental protocol of fecal hormones extraction and dosage. For the first two objectives, measures of fecal glucocorticoids metabolites, behavioral and environmental data of two wild populations of capuchin monkeys were taken. One in the Carlos Botelho State Park/São Paulo (PECB) and the other in Boa Vistas Farm/Piauí (FBV). For the experimental protocol validation an ACTH and dexamethasone challenge was executed with captive capuchin monkeys. Generalized Linear Mixed Models (MLGM) analysis showed a significant difference between basal levels of MFGs of the two populations, being the FBV the one with higher values. For that population there was also an effect of fruit availability in the habitat, frequency of encounters with other animals species and copulations in the mensal variation of the MFGs basal levels. There was no significant effect of the studied variables in the mensal basal levels variation of MFGs in the PECB population. The individual analyses showed that agonistic interactions among group members were the major cause of MFGs\' peaks in the studied subjects. Other major factors were females in proceptive period and copulations, that caused peaks not only in adult males, but also in juvenile males and the females themselves. The ACTH and dexamethasone challenge results validated the experimental protocol of hormones extraction and dosage. The obtained results are in agreement with previous researches that reveled marked differences in the social system of the two populations, specially in females social relationships that varied in accordance with the two areas ecological differences. The results also suggested that it is not possible to define reference values of MFGs\' basal levels for the Sapajus genus once the two populations are significantly different in this aspect. This work is just the beginning of a long endeavor to comprehend stress in wild capuchin monkeys, nevertheless it presents the first glimpse to the understanding of the natural stressors for those animals and how they impact the MFGs\' levels
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Barra, Cristina Botelho. "Determinação do valor de referência para o cortisol basal sérico em população pediátrica sem doença adrenal." Universidade Federal de Minas Gerais, 2012. http://hdl.handle.net/1843/BUOS-8UAQPC.
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The basal cortisol measurement reflects the hypothalamic-pituitary-adrenal activity. It is used in assessing the integrity of the axis response, mainly in patients undergoing long periods of glucocorticoid treatment, because they have a higher chance of adrenal suppression. In pediatrics, adrenal suppression should always be considered in children who received supraphysiologic glucocorticoid doses for more than two weeks. Under these conditions, there is an increased risk of adrenal crisis, even in the presence of moderate stressors. The cortisol values below the reference range are suggestive of adrenal dysfunction. Therefore, this evaluation may be crucial in the decision-making process. The same reference values of normal serum cortisol have been used, in practice, for adults and children. However, results obtained from an adult population may not be suitable for pediatric patients and can negatively impact the quality of this evaluation in childhood. Thus, the main objective of this study was to contribute to the assessment of basal cortisol levels in pediatric subjects. The assay method used by the reference laboratory for serum cortisol was the chemiluminescent enzyme immunoassay. The series was based on 120 reference individuals from 4-19 years old. The results obtained for cortisol were correlated with gender, age and pubertal maturation. The cortisol results profile was also studied for 95 children and adolescents from 0-19 years old, healthy or with persistent asthma and wheezing, prior to inhalation therapy. In the study, baseline serum cortisol increased with age and pubertal maturation. Serum cortisol showed no differences based on gender. Children from 0-3 years old with asthma and wheezing showed a great range of cortisol values, whereas older children showed less variation. The positive correlation between age and serum cortisol was observed only in children older than 3 years and it was more evident after 5 years old. Adolescents who were 16 to 19 years old had higher serum cortisol values than younger ones and also than those with incomplete pubertal development. The reference limits (2.5 and 97.5 percentiles) for the basal serum cortisol in the population of healthy subjects were: 2.97 g/dL [90% CI (1.44, 3.69)] and 23.4 g/dL [90% CI (16.3, 24.6)]. Thus, the interval for baseline serum cortisol of 4.46 to 22.7 g/dL being used up until now by the reference service was considered inappropriate for the pediatric population under study. The results presented here and the literature research suggest that reference intervals for serum cortisol should be determined specifically to the pediatric population.A medida do cortisol basal reflete a atividade hipotalâmica-hipofisária-adrenal. É utilizada na avaliação da integridade da resposta do eixo, principalmente em pacientes submetidos a longos períodos de tratamento glicocorticoide, por apresentarem maior risco de supressão adrenal. Em pediatria, a supressão adrenal deve ser sempre considerada em crianças que receberam doses suprafisiológicas de glicocorticoides por mais de duas semanas. Nessas condições, há risco de crise adrenal mesmo em vigência de agentes estressores moderados. Os valores de cortisol obtidos abaixo do intervalo de referência são sugestivos de disfunção adrenal. Sendo assim, a dosagem do cortisol basal pode ser crucial no processo de tomada de decisão. Os mesmos valores de referência de normalidade do cortisol basal sérico para adultos e crianças têm sido utilizados na prática. Contudo, resultados obtidos a partir de uma população adulta podem não ser adequados para a faixa etária pediátrica, comprometendo a qualidade das avaliações feitas na infância. Dessa forma, o objetivo principal do presente estudo é contribuir para essa adequação. Os valores de referência para o cortisol basal sérico foram determinados para indivíduos da faixa etária pediátrica. O método utilizado para a dosagem do cortisol pelo laboratório de referência foi o imunoensaio enzimático quimioluminescente. A casuística foi fundamentada em 120 indivíduos de referência de 4-19 anos. Os resultados obtidos para o cortisol foram correlacionados com o gênero, idade e grau de maturação sexual. O perfil de variações do cortisol basal também foi estudado em 95 crianças e adolescentes de 0-19 anos saudáveis ou com asma persistente e síndromes sibilantes, previamente à terapia inalatória. Na casuística, o cortisol basal sérico aumentou com a idade e com a maturação sexual e não apresentou diferenças baseadas no gênero. Crianças com asma ou síndromes sibilantes de 0-3 anos apresentaram grande amplitude de valores de cortisol, conquanto crianças mais velhas apresentaram menor variação. A correlação positiva entre idade e cortisol sérico foi observada apenas após os 3 anos, sendo mais expressiva após os 5 anos. Adolescentes de 16 a 19 anos apresentaram valores de ortisol sérico mais elevados que indivíduos mais jovens e com desenvolvimento sexual incompleto. Os limites de referência (percentis 2,5 e 97,5) para o cortisol basal sérico na população de indivíduos saudáveis foram: 2,97 g/dL [IC 90% (1,44; 3,69)] e 23,4 g/dL [IC 90% (16,3; 24,6)]. Dessa forma, o intervalo para o cortisol basal sérico de 4,46-22,7 g/dL,utililizado até o momento no serviço de referência, foi considerado inadequado para a população pediátrica em estudo. Os resultados apresentados e a experiência na literatura sugerem que intervalos de referência para o cortisol sérico, específicos para a população pediátrica, devem ser determinados.
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Chellew, Gálvez Karin. "The effect of progressive muscle relaxation in the basal cortisol response of high and low neurocitism students." Doctoral thesis, Universitat de les Illes Balears, 2015. http://hdl.handle.net/10803/291561.
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Els trets de personalitat juguen un paper rellevant en les diferències individuals en la secreció
del cortisol. No obstant això, la naturalesa i els mecanismes subjacents d'aquesta relació tot i
romanen poc clars. El cortisol, producte final de l'eix Hipotàlem-pituïtari-Adrenal (HPA), és un
glucocorticoide que el nostre cos secreta naturalment seguint un pronunciat cicle diürn, amb
nivells elevats davant de situacions particularment estressants (reactivitat del cortisol). La
present tesi doctoral té com a objectiu elucidar com els trets de personalitat influeixen en la
resposta del cortisol d'estudiants universitaris en tres condicions diferents: estressant, basal i
de relaxació. Aquest treball comença avaluant la resposta del cortisol davant d'una situació
estressant (parlar en públic) en estudiants de psicologia. Esperàvem que la reactivitat del
cortisol estigués positivament relacionada amb Obertura, Amabilitat i Responsabilitat, i
negativament amb Extraversió, Neuroticisme i Psicoticisme. En el nostre segon estudi,
avaluem el perfil de secreció de cortisol basal en estudiants universitaris amb puntuacions
extremes en Neuroticisme (N) tractant de demostrar una associació teòrica esperat entre N i la
secreció de cortisol diürn. Pensàvem que participants amb puntuacions altes en N exhibirien
constantment nivells elevats de cortisol diürn basal comparat amb aquells amb puntuacions
baixes en N. Finalment, volíem examinar si una setmana de Relaxació Muscular Progressiva
Abreujada (APMR) era eficaç per reduir nivells totals d'estrès psicològic i fisiològic de
participants amb puntuacions extremes en N. Els nostres resultats confirmen, en primer lloc,
que parlar en públic augmenta significativament la secreció de cortisol en comparació amb una
activitat acadèmica no estressant. A més a més, Responsabilitat ha estat associada amb un
augment significatiu dels nivells de cortisol, i Psicoticisme amb una a la baixa. En segon lloc,
trobem que Neuroticisme ha estat associat amb una elevada secreció de cortisol davant de
situacions d'estrès diari, encara que només després dels primers 45 min. després de despertar
(CAR). Aquesta associació ha estat independent del gènere i edat dels participants, si
fumaven o no, l'hora de despertar, o del dia de l'estudi. Finalment, en tercer lloc, APMR és una
eina eficaç per disminuir tant l'estrès psicològic com fisiològic en tots els participants,
independentment de puntuacions altes o baixes en Neuroticisme, el gènere, o l'edat dels participants.Los rasgos de personalidad juegan un papel relevante en las diferencias individuales en la secreción del cortisol. Sin embargo, la naturaleza y los mecanismos subyacentes a esta relación aún permanecen poco claros. El cortisol, producto final del eje Hipotálamo-Pituitario- Adrenal (HPA), es un glucocorticoide que nuestro cuerpo secreta naturalmente de acuerdo a un ciclo diurno pronunciado, con niveles elevados ante situaciones estresantes (reactividad del cortisol). El objetivo de la presente tesis doctoral ha sido elucidar cómo los rasgos de personalidad influyen en la respuesta del cortisol de estudiantes universitarios en tres condiciones distintas: estresante, basal y de relajación. Este trabajo comienza evaluando la respuesta del cortisol ante una situación estresante (hablar en público) en estudiantes de psicología. Esperábamos que la reactividad del cortisol estuviera positivamente relacionada con Apertura, Amabilidad y Responsabilidad, y negativamente con Extraversión, Neuroticismo y Psicoticismo. En nuestro segundo estudio, evaluamos el perfil de secreción de cortisol basal en estudiantes universitarios con puntuaciones extremas en Neuroticismo (N). Con ello pretendíamos demostrar de forma experimental una asociación planteada a nivel teórico entre N y secreción de cortisol diurno. Así esperábamos que los participantes con puntuaciones altas en N exhibieran niveles elevados de cortisol diurno basal comparado con participantes con puntuaciones bajas en este rasgo. Por último, queríamos examinar si una semana de Relajación Muscular Progresiva Abreviada (APMR) era efectiva en reducir los niveles totales de estrés psicológico y fisiológico de participantes con puntuaciones extremas en N. Nuestros resultados confirman, en primer lugar, que hablar en público aumenta significativamente la secreción de cortisol en comparación con una actividad académica no estresante. Además, Responsabilidad se asoció con un aumento significativo de la respuesta de cortisol, y Psicoticismo con una respuesta a la baja. En segundo lugar, encontramos que altos niveles de Neuroticismo se asociaron con una secreción elevada de cortisol en situaciones de estrés diario, aunque solo después de los primeros 45 min después de despertar (CAR). Esta asociación fue independiente del género y edad de los participantes, si fumaban o no, de la hora de despertar, o del día del estudio. Por último, en tercer lugar, APMR fue eficaz en disminuir tanto el estrés psicológico como fisiológico en todos los participantes, independientemente del género, la edad o de la puntuación de Neuroticismo de los participantes.
Personality traits play a significant role in individual differences in cortisol response (LeBlanc, Ducharme, & Thompson, 2004). However, the nature and underlying mechanisms of the relationship between cortisol secretion and personality traits still remain unclear. Cortisol, an end product of the Hypothalamic-Pituitary-Adrenal axis (HPA), is a glucocorticoid that our body naturally secretes according to a pronounced diurnal cycle with increased values under stressful situations (cortisol reactivity). The aim of the present PhD dissertation was to elucidate how personality traits influence the cortisol secretion of undergraduate students in three different conditions; stressful, baseline, and relaxation. This work began by evaluating the cortisol response facing a stressful situation (public speaking) of psychology students. We believed that cortisol reactivity would be positively related to Openness, Agreeableness, and Conscientiousness, and negatively to Extraversion, Neuroticism and Psychoticism. In our second study, we assessed the baseline cortisol in students with extreme scores in Neuroticism (N) attempting to prove a theoretical expected association between N and diurnal cortisol secretion. We postulated that high N participants would display elevated diurnal background levels of cortisol compared to low N participants. Finally, we examined whether one week of Abbreviated Progressive Muscle Relaxation (APMR) was effective in reducing overall levels of psychological and physiological stress of high- and low-N participants. Our results confirmed, firstly, that public speaking significantly increased cortisol secretion when compared to a non-stressful academic activity. In addition, Conscientiousness was associated with an enhanced cortisol response to public speaking, and Psychoticism with a blunted one. Secondly, we found that high levels of Neuroticism were associated with elevated cortisol secretion on daily stress, but only after the first 45 min following awakening (CAR). This association was independent of sex and age, smoking status, awakening time, and day of study. Finally, in third place, APMR was effective in decreasing both psychological and physiological stress in all participants independently of their N-score, gender, or age.
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Strahler, Jana. "Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-60778.
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Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler)
The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies have been published that introduced salivary cortisol to assess HPA axis activity and therefore strengthens its role as an easy obtainable biomarker in stress research that can be monitored easily and frequently. Recent findings suggest a possible surrogate marker of autonomic activity due to autonomic innervation of salivary glands: salivary alpha-amylase (sAA). Up to date, additional methodological research is needed for a better understanding of the advantages and disadvantages of sAA activity in comparison to already established markers of ANS activity. The aim of the present thesis is to further our knowledge of confounders of sAA activity under basal and acute stress conditions and to strengthen the validity of this enzyme as an easy obtainable alternative for ANS testing.
After introducing classical and modern stress concepts and stress system physiology (chapter 2), the reader is acquainted with anatomical basics of salivary gland innervation and secretion of salivary proteins, including sAA, due to autonomic innervation (chapter 3 and 4). Afterwards, a more nuanced review of methodological considerations of sAA determination shows gaps of knowledge concerning its usefulness as a marker of ANS activity (chapter 5). Given the fact that the integration of sAA into developmental and aging research is a relative recent phenomenon, several issues have to be addressed before a final conclusion could be drawn. Therefore, we conducted a series of studies incorporating these considerations regarding behavioral correlates of inter- and intraindividual differences in sAA activity with a special emphasis on older adults.
Chapter 7 deals with sAA activity under psychological stress conditions in different age groups. Since vulnerability to disease and disease prevalence patterns change with age, it is important to investigate stress reactivity of people in different age groups. We therefore investigated children between 6 and 10 years, because childhood is a sensitive period of growth and development, and thus plays an important role for later life health. Young adults were included to represent the most studied human age group as a reference. Older adults between 59 and 61 years were investigated, because at this age the course is set for the further development of a person’s health in later life, and because autonomic stress responses in older age might be important determinants of cardiovascular and inflammatory aging. Our goal is to test for associations of sAA with more established stress system markers, i.e., salivary cortisol as outcome measurement of HPA reactivity, heart rate (HR) and heart rate variability (HRV) as markers for autonomic reactivity, and to directly compare these responses between different age groups across the life span. Secretion of sAA and cortisol was repeatedly assessed in 62 children, 78 young adults, and 74 older adults after exposure to a standardized psychosocial stressor, the Trier Social Stress Test. In addition, cardiovascular activity was measured in both adult groups. Older adults showed attenuated sAA, HR, and HRV responses. Furthermore, we found higher sAA but lower cortisol at baseline as well as lower sAA and cortisol responses in children. Age by sex interactions were observed only for cortisol with higher responses in older male participants. No associations between the parameters were found. Results in children and young adults confirm previous results. Overall, findings implicate sAA as an alternative or additional autonomic stress marker throughout the life span, with marked and rapid responsiveness to stress in three relevant age groups.
The impact of age and chronic stress on basal sAA activity is the center of interest in chapter 8. We therefore assessed diurnal profiles of sAA and salivary cortisol in 27 younger and 31 older competitive ballroom dancers as well as 26 younger and 33 older age- and sex-matched controls. According to the Allostatic Load concept, repeated, non-habituating responses to social-evaluative conditions, which characterize the lives of competitive ballroom dancers, should be associated with stress system dysregulations. Furthermore, we expect to see an increased sympathetic drive associated higher overall alpha-amylase activity in older adults. Analyses revealed an elevated daily overall output of sAA in older adults while there was no effect of age on mean cortisol levels. Alterations of diurnal rhythms were only seen in younger male dancers showing a flattened diurnal profile of sAA and younger dancers and female older dancers showing a blunted diurnal rhythmicity of cortisol. Furthermore, we found a negative correlation between summary indices of basal sAA and the amount of physical activity. In conclusion, higher overall output of sAA in older adults was in line with the phenomenon of a “sympathetic overdrive” with increasing age. Furthermore, a lower output of sAA in people who are more physical active was in line with the hypothesis of an exercise-induced decrease of sympathetic activity.
Taken together, results of chapter 7 and 8 show a clear impact of age on sAA activity, either under acute stress or basal conditions. One problem when integrating sAA into developmental and aging research is the use of adrenergic agonists and antagonists what is very common in older adults, i.e. antihypertensive drugs (AD). As well, the previously shown sympathetic overactivity that occurs with normal aging is associated with higher blood pressure (BP). Therefore, chapter 9 deals with a possible impact of high BP and AD on diurnal sAA activity in 79 older adults (33 normotensive adults, 16 medicated vs. 45 hypertensive adults, 34 medicated). Results showed a pronounced rhythm of sAA in all groups. Diurnal profiles differed significantly between men and women with men lacking the typical decrease of sAA in the morning and showing more pronounced alterations throughout the day. An effect of AD on sAA profiles and area under the curve values indicates that subjects not using AD´s show a heightened diurnal profile and a higher total output of sAA. Descriptively, this was also true for hypertensive older adults. Hypertensive subjects and those not using AD showed the highest diurnal output of sAA and the steepest slope. In sum, our results show an impact of antihypertensive medication and a difference between normotensive and hypertensive subjects on characteristics of diurnal sAA activity. Hence, findings are of particular interest in research using sAA as a prognostic indicator of pathological states and processes.
Given the fact that hypertension was also shown to be associated with substantial changes of transmitters within the suprachiasmatic nucleus (SCN) - the “biological clock” that receives photic input from retinal glands via the retinohypothalamic pathway - and an altered output from the SCN to the sympathetic nervous system, we broaden the idea of a possible effect of different lighting conditions on morning sAA profiles in chapter 10. In a counterbalanced within-subjects design six men and 16 women of different ages collected sAA morning profiles on two consecutive days with leaving their shutters closed on the one day (= dark) and open their shutters on the other day (= bright). We were able to replicate earlier findings of light-induced changes of salivary cortisol with higher responses during the bright condition. On either day, women showed larger cortisol increases than men. Despite multisynaptic autonomic connections arising from the SCN projecting to multiple organs of the body, we could not find an effect of sunlight on sAA morning profiles. Evidence for circadian clock gene expression in human oral mucosa might account for this result and indicates that peripheral oscillators may act more like integrators of multiple different time cues, e.g. light, food intake, instead of a “master” oscillator (SCN).
Results of chapter 7 to 10 provide clear evidence that sAA is heightened in states of autonomic arousal, i.e. stress, aging and hypertension, and that its circadian rhythmicity seems to be regulated rather integrative than directly via efferent input from hypothalamic SCN neurons. In chapter 11 this thesis tries to approach one central question: What is the biological meaning of the findings made? According to this enzyme´s anti-bacterial and digestive action short term changes might not have a biological meaning itself but rather reflect just a small part of multiple coordinated body responses to stressful stimuli. While the sympathetic branch of the ANS mainly stimulates protein secretion, the parasympathetic branch stimulates saliva flow. Acute stress responses might therefore be interpreted as reflecting predominant sympathetic activity together with parasympathetic withdrawal. The same mechanism could also be suitable for the finding of higher diurnal levels of sAA in older adults or hypertensive subjects reflecting a higher peripheral sympathetic tone in these groups. Diurnal profiles of sAA itself may reflect circadian changes in autonomic balance. Circadian rhythms are of great advantage since they enable individuals to anticipate. This pre-adaptation enables the individual to cope with upcoming demands and challenges. Our finding of a relationship between sAA and salivary cortisol what strengthens the relevance of glucocorticoids that were previously shown to be able to phase shift circadian rhythms in cells and tissue. Within a food-related context there is evidence that decreasing levels of sAA in the morning could reflect increases of feeling hungry since sAA systematically increases during food consumption and with the subjective state of satiety. So far, much more research is needed to identify underlying physiological mechanisms of circadian sAA rhythmicity.
Taking the next step, future studies will have to focus on the integration of sAA assessment into longitudinal studies and different disease states to prove its applicability as a marker of sympathetic neural functioning in the genesis and prognosis of disease.
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Wuethrich, Stephanie Nadya. "The modulatory role of morning and afternoon basal cortisol levels on neural activation changes in healthy young males performing an n-back working memory task : an exploratory fMRI study." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101808.
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Human cognitive processes, such as learning and memory, are particularly vulnerable to the effects of cortisol, the human stress hormone. In the field of magnetic resonance imaging (MRI) the different cortisol characteristics are neither controlled nor accounted for. This study will aim to investigate, by means of functional MRI, the effects of morning and afternoon cortisol levels on neural activation changes in response to a working memory task in young males. We hypothesized a significant difference between morning and afternoon subjects' cortisol levels and neural activation patterns in relation to the task. Nineteen young males were recruited, 9 for the morning group and 10 for the afternoon group. Cortisol levels, neuronal activation, and behavioural measurements (correct percentage of hits and reaction time) were assessed during the task. Six saliva samples were taken during the experiment at various time intervals. As expected, morning cortisol levels were higher than afternoon cortisol levels. Results indicate that the afternoon group had significantly slower reaction time on the frontal task compared to the morning group, whilst the percentage of correct hits did not differ. Furthermore, we observed an increased range of neural activation in the morning group compared to the afternoon group. This study demonstrates the impact of time of day of testing (i.e. different cortical levels) on neural activation in functional MRI experiments. It is important for investigators using this technique to be aware of and control for this variable.
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Hutton, Elizabeth Anne May. "Somatosensory cortical input to the basal ganglia." Thesis, University of Edinburgh, 1998. http://webex.lib.ed.ac.uk/abstracts/hutton01.pdf.
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Morris, Laurel Sophia. "Cortical-basal ganglia circuits : control of behaviour and alcohol misuse." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/268015.
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Highly organised and differentiated neural circuits form and unite to link the cortex with the basal ganglia and thalamus to mediate movement, cognition and behaviour. Previous assertions that the basal ganglia primarily acted to filter cortical information to facilitate motor outputs only have since given way to an understanding of the basal ganglia as a relay and gating structure with functionally and structurally segregated inputs, functions and outputs. Thus, cortical – basal ganglia circuits can be segregated into three broadly separable functional domains mediating motor (primary and supplementary motor cortex (SMA) and putamen), cognitive (dorsolateral prefrontal cortex (dlPFC) and caudate), and limbic (ventromedial prefrontal cortex and ventral striatum (VS)) processes. In addition, cognitive and behavioural programs that pass through the cortical – basal ganglia circuitry can be subject to filtering by the subthalamic nucleus (STN), which receives direct projections from the cortex. This work first demonstrated the functional organisation of segregated intrinsic cortical – basal ganglia circuits in humans, alongside a detailed map of functional subzones within STN, a small and technically inaccessible midbrain structure. The behavioural relevance of the defined cortical – basal ganglia circuits was investigated by examining the cognitive constructs of impulsivity and compulsivity. Waiting impulsivity, a tendency towards rapid premature responses that has been associated with compulsive drug use, was associated with connectivity between limbic regions including subgenual anterior cingulate cortex, VS and STN. However, motor impulsivity, in the form of stopping ability, was associated with motoric regions including pre-SMA and STN. Compulsivity was captured as deficits in: reversal learning, implicating lateral orbitofrontal cortex; attentional shifting, implicating dlPFC; and habit learning, implicating SMA. Neural circuit changes were also examined in individuals with alcohol dependence and binge drinkers. Waiting impulsivity was elevated in both groups and the functional connectivity, microstructural integrity and anatomical connectivity of the neural circuit underlying waiting impulsivity were associated with problematic drinking behaviours in both groups. Together, this work establishes that discrete functional subzones of small subcortical regions can be differentiated in humans and that their behavioural correlates can be similarly mapped. The definition of intrinsic network architecture underlying a particular behaviour and the demonstration its disturbance in psychiatric groups will crucially inform the development of future diagnostic and therapeutic models.
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Furuta, Takahiro. "A novel modulatory system in the cortico-basal-ganglia loop." 京都大学 (Kyoto University), 2003. http://hdl.handle.net/2433/149163.
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Oldenburg, Ian Anton. "Basal Ganglia Modulation of Cortical Firing Rates in a Behaving Animal." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13094354.
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Motor cortex, basal ganglia (BG), and thalamus are anatomically arranged in a recurrent loop whose activity is hypothesized to be involved in the selection of motor actions. Direct (dSPN) and indirect (iSPN) striatal projection neurons receive excitatory input from cortex, and are thought to oppositely modulate cortical activity via BG output to thalamus. Here, we test the central tenets of this model in head-restrained mice performing an operant conditioning task using optogenetic manipulation of dSPNs and iSPNs to determine the effects of activity in each pathway on primary motor cortex. We find that dSPN and iSPN activation has bidirectional, robust, and rapid effects on motor cortex that are highly context-dependent, with distinct effects of each pathway during quiescent and active periods. Thus, the effects of activity in each pathway are at times antagonistic and consistent with classic models, whereas in other behavioral contexts the two pathways will work in the same direction or have no effect at all. In a separate but related project, we describe a direct projection from the globus pallidus externa (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC), which is not typically included in models of BG function. Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projection patterns and expression of choline acyteltransferase (ChAT), a genetic marker for the neurotransmitter acetylcholine. These cholinergic GP cells receive basal ganglia input and bidirectionally modulate firing in FC of awake mice. Since GP-FC cells receive dopamine sensitive inhibition from iSPNs and dSPNs, this circuit reveals a pathway by which neuropsychiatric pharmaceuticals can act in the BG and yet modulate frontal cortices. Together, these two projects expand our understanding of the complexities of basal ganglia circuitry and its interactions with cortex.
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Sharott, Andrew David. "The role of oscillation population activity in cortico-basal ganglia circuits." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445058/.
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The basal ganglia (BG) are a group of subcortical brain nuclei that are anatomically situated between the cortex and thalamus. Hitherto, models of basal ganglia function have been based solely on the anatomical connectivity and changes in the rate of neurons mediated by inhibitory and excitatory neurotransmitter interactions and modulated by dopamine. Depletion of striatal dopamine as occurs in Parkinson's Disease (PD) however, leads primarily to changes in the rhythmicity of basal ganglia neurons. The general aim of this thesis is to use frontal electrocorticogram (ECoG) and basal ganglia local field potential (LFP) recordings in the rat to further investigate the putative role for oscillations and synchronisation in these structures in the healthy and dopamine depleted brain. In the awake animal, lesion of the SNc lead to a dramatic increase in the power and synchronisation of P-frequency band oscillations in the cortex and subthalamic nucleus (STN) compared to the sham lesioned animal. These results are highly similar to those in human patients and provide further evidence for a direct pathophysological role for p-frequency band oscillations in PD. In the healthy, anaesthetised animal, LFPs recorded in the STN, globus pallidus (GP) and substantia nigra pars reticulata (SNr) were all found to be coherent with the ECoG. A detailed analysis of the interdependence and direction of these activities during two different brain states, prominent slow wave activity (SWA) and global activation, lead to the hypothesis that there were state dependant changes in the dominance of the cortico-subthalamic and cortico-striatal pathways. Multiple LFP recordings in the striatum and GP provided further evidence for this hypothesis, as coherence between the ECoG and GP was found to be dependent on the striatum. Together these results suggest that oscillations and synchronisation may mediate information flow in cortico-basal ganglia networks in both health and disease.
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Lim, Eugene J. (Eugene Jungsud) 1980. "An engineering model of lower thalamo-cortico-basal ganglionic circuit function." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/28458.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (leaves 59-60).
An engineering model of lower thalamo-cortico-basal ganglionic circuit functionality was extended and tested. This model attempts to explain the circuitry of the basal ganglia, examine its functional properties, and integrate these properties into an understanding of the diseases of the basal ganglia, such as Parkinson's disease and Huntington's disease. Using this model, simulations of various movements were developed, specifically those of the following: 1) one-step, cruise movements, 2) asynchronous, cruise movements, and 3) sequential cruise movements. Results of these movements include simulated movements of both normal patients and patients with movement disorders.
by Eugene J. Lim.
M.Eng.
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Doig, Natalie M. "Cortical and thalamic innervation of striatum." Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572466.
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The basal ganglia are a collection of sub-cortical nuclei involved in the execution of a range of motor and cognitive behaviours. The striatum is the input nucleus of the basal ganglia, receiving major excitatory innervation from the cerebral cortex and intralaminar thalamic nuclei. The main target of these two pathways are the principal striatal neurons, the medium-sized spiny neurons (MSNs), which are subdivided based on their axonal targets and the expression of molecular markers. Direct pathway neurons project to the output nuclei of the basal ganglia and express the D, dopamine receptor subtype, whereas indirect pathway MSNs project to the output nuclei via the globus pallidus, and express the D2 receptor. The striatum also contains interneurons that are essential in processing information within striatum; the cholinergic interneuron is of particular interest due to its role in reward-related behaviour. The aim of this study was to examine the cortical and thalamic innervation of subtypes of striatal neurons. To examine whether the cortical or thalamic afferents selectively innervate direct or indirect pathway neurons, transgenic mice expressing GFP under either the D, or D2 receptor promoter were used. Striatal sections from these mice were immunostained to reveal the GFP and selective markers of the cortical and thalamic afferents, VGluTI and VGluT2, respectively. A quantitative electron microscopic examination ofsynaptic connectivity was carried out. The results indicate that there is no selectivity of either the cortical or thalamic pathway for D, or D2 expressing MSNs. Thus both direct and indirect pathway MSNs are involved in the processing of both cortical and thalamic information The cortical and thalamic innervation to cholinergic interneurons was also examined. Stimulation of cortex and thalamus in vivo in anaesthetised rats resulted in short-latency excitatory responses in identified cholinergic interneurons, indicative of monosynaptic connections. After recording, cholinergic interneurons were filled with neurobiotin. The synaptic innervation from cortex and thalamus was then examined in two individual, electrophysiologically characterised, and neurochemically identified cholinergic interneurons. One neuron received input from both cortex and thalamus, whereas the other neuron received input from the thalamus only. These results provide anatomical and physiological data illustrating how the excitatory inputs to striatum innervate cholinergic interneurons.
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Moore, Holly. "Modulation of Cortical ACh Release by GABAa-dopamine Receptor Interactions in the Basal Forebrain /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487868114114352.
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Arakaki, Takafumi. "Collective dynamics of basal ganglia-thalamo-cortical loops and their roles in functions and dysfunctions." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066123/document.
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Les ganglions de la base (GB) sont principalement connus pour leurs fonctions motrices, mais présentent également des fonctions non motrices. Sans surprise, il a été montré qu’ils sont impliqués dans des troubles moteurs tels que la maladie de Parkinson ou les dystonies. Des études récentes suggèrent que les GB jouent également un rôle prépondérant dans des maladies “non-motrices” telles que l’épilepsie d’absence , qui est une épilepsie généralisée non convulsive. Dans l’ensemble de ces dysfonctions des GB, les symptômes sont accompagnés de différents patrons oscillants d’activité neuronale souvent synchronisés entre les différents noyaux des GB, le cortex et d’autres aires cérébrales. Comment les GB peuvent-ils favoriser ou soutenir ces différentes activitées oscillantes?Des expériences récentes ont montré le rôle clé joué par les GB dans l’épilepsie d’absence et remettent en question le point de vue traditionnel selon lequel les circuits thalamo-corticaux sont responsables des crises d’absence. Nous proposons une nouvelle théorie selon laquelle les rétroactions opérées par les GB sur l’activité corticale rend le réseau bistable et entraîne les patrons d’activité oscillante qui apparaîssent pendant les crises. Notre théorie est compatible avec l’ensemble des résultats expérimentaux connus et elle prédit qu’un input excitateur transitoire sur le cortex peut terminer prématurément les crises d’absence. Nous présentons ici des résultats préliminaires en accord avec cette prédiction.De multiples fréquences des oscillations d’activité sont observées dans la maladie de Parkinson au sein des GB, telles que les fréquences correspondant aux tremblement des membres ou encore les oscillations béta. Nous montrons que notre model peut générer des oscillations à différentes échelles temporelles qui coïncident avec les fréquences des oscillations dans la maladie de Parkinson. Notre théorie peut rendre compte des oscillations observées dans la maladie de Parkinson et dans l’epilépsie d’absence dans un cadre théorique unifié et suggère deux scénarios pour expliquer les multiples fréquences des oscillations d’activité, à la fois pathologiques et fonctionnellesThe Basal Ganglia (BG) are thought to be involved primarily in motor but also in non-motor functions. Unsurprisingly, the BG are shown to be involved in motor dysfunctions such as Parkinson's disease or dystonia. More recent studies suggest the key role of the BG in "non-motor" diseases such as absence epilepsy which is a generalized non-convulsive epilepsy. In these diseases, symptoms accompany various oscillatory patterns of neural activity often synchronized across the BG, cortex and other brain areas. How can the BG support these different kinds of oscillatory patterns?Recent experiments have highlighted the key role of the BG in absence seizures and question the traditional view in which thalamocortical circuits underlie absence seizures. We propose a novel theory according to which the feedbacks of cortical activity through BG make this network bistable and drive the oscillatory patterns of activity occurring during the seizures. Our theory is compatible with virtually all known experimental results and it predicts that well-timed transient excitatory inputs to the cortex advance the termination of absence seizures. We report preliminary experimental results consistent with this prediction.Multiple oscillatory frequencies are observed in Parkinsonian BG such as the frequencies of the limb tremor and the beta oscillations. We show that our model can generate oscillations with multiple timescales which resemble Parkinsonian oscillations. Our theory can model the oscillations in Parkinson's disease and absence epilepsy in a unified framework and points to two scenarios to explain multiple frequencies of pathological and functional oscillations
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Fadel, James R. "Modulation of cortical acetylcholine release by glutamate, gamma-amino butyric acid, and noradrenaline receptor mechanisms within the basal forebrain : studies on basal and behaviorally-activated release /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487953204280146.
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Oswal, Ashwini. "Functional and clinical relevance of oscillatory activity within cortico-basal-ganglia circuits in Parkinson's disease." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:70157526-9b5a-42d2-ab57-b654f561dcf3.
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Over the past 20 years there have been significant advances in our understanding of how synchronised neural oscillations relate to cognitive and motor processes both in health and in neurological disease. Oscillations can be considered from the point of view of being the observations of the latent dynamical properties of interacting populations of neurones. With this in mind it becomes evident that their study may inform about underlying functional architectures and principles governing motor and cognitive control. Cortico-basal-ganglia circuits are canonical feedback loops between cortical and sub-cortical structures, with well-defined anatomy which makes them ideal for the study of oscillatory phenomena. Moreover, these circuits are known to play crucial roles in motor and cognitive processes such that impairments of their normative function may lead to neurological disease states. In this thesis I focus on insights about oscillatory function from cortical-basal ganglia recordings in Parkinson's disease. I will present evidence from studies showing that the roles of beta (15-30 Hz) and gamma (60-90 Hz) oscillatory activities in motor control are intricately linked to task specific cognitive-motor demands. Furthermore, the timing of activities within these frequency bands relative to movement reveals how distinct spectral phenomena may relate to distinct aspects of cognitive and motor processing. An intricately related aim of this thesis is to begin to establish how the preferred frequencies of interaction and the topographies of long range oscillatory networks within cortico-basal-ganglia loops relate to specific clinical symptoms. In this regard, I will present data revealing the modulation of cortico-basal ganglia coupling by movement, and Parkinson's disease therapies such as levodopa and Deep Brain Simulation (DBS). Novel methodological developments that facilitate such insights are presented. Finally I discuss how these insights contribute to existing understanding of the pathophysiology of Parkinson's disease, in addition to suggesting novel future therapeutic strategies for DBS.
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Usui, Keiko. "Processing of Japanese morphogram and syllabogram in the left basal temporal area : electrical cortical stimulation studies." Kyoto University, 2005. http://hdl.handle.net/2433/144788.
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Kyoto University (京都大学)0048
新制・課程博士
博士(医学)
甲第11464号
医博第2887号
新制||医||900(附属図書館)
23107
UT51-2005-D214
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授 髙橋 良輔, 教授 金子 武嗣, 教授 河野 憲二
学位規則第4条第1項該当
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Manns, Ian Douglas. "The role of basal forebrain neurons in the modulation of cortical activity : a physiological and anatomical examination." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37653.
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The basal forebrain is essential for stimulating the cortical activation associated with waking and paradoxical sleep, yet it is also important for attenuating cortical activation and promoting SWS. Heterogeneous neuronal groups of this region, which include cortically projecting cholinergic, GABAergic and other noncholinergic/nonGABAergic possibly glutamatergic neurons, may mediate these different processes. In order to understand this differential modulation, the discharge profiles of the neuronal groups must be studied in association with cortical activity.Juxtacellular recording and labeling of neurons in the magnocellular preoptic area (MCPO) and substantia innominata (SI) of the basal forebrain with Neurobiotin (Nb) followed by immunohistochemical staining for neurotransmitter enzymes revealed the discharge properties of identified neurons during slow irregular electroencephalographic (EEG) activity and stimulation-induced cortical activation in urethane-anesthetized rats. Choline acetyltransferase immunopositive (ChAT+) neurons increased their average discharge rate with stimulation, and the majority shifted from an irregular tonic discharge during slow irregular EEG activity to a rhythmic burst discharge during activated and rhythmic EEG activity. In contrast, a minority of glutamic acid decarboxylase immunopositive (GAD+) neurons increased their average discharge rate, while the majority made up of specific subgroups decreased their average discharge rate in association with stimulation-induced cortical activation. Another group of neurons that discharged in rhythmic clusters during cortical activation was both ChAT and GAD immunonegative. The possibility that these were glutamatergic was investigated by immuno-staining for phosphate-activated-glutaminase (PAG), the synthetic enzyme for neurotransmitter glutamate. A parallel study determined that a significant proportion of cortically projecting basal forebrain neurons contained PAG. The rhythmically discharging ChAT and GAD immunonegative cells were PAG+. Their rhythmic discharge occurred at the same frequency as that of the cholinergic and GABAergic neurons and was simultaneously correlated with the activity of the olfactory bulb and that of other limbic neocortical regions.
Together these findings indicate that cholinergic and GABAergic neurons, together with glutamatergic neurons function in a parallel manner to mediate cortical activation including rhythmic theta and high frequency gamma activity. Distinct subgroups of GABAergic neurons may be involved in dampening cortical activation and mediating the slow irregular cortical activity of slow wave sleep.
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Eusebio, A. "Mechanisms and consequences of beta oscillatory activity propagation in the basal ganglia-cortical network in Parkinson's disease." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1356885/.
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Excessive neural synchronisation in the beta frequency band (10-35 Hz) is a hallmark of Parkinson’s disease (PD) but the mechanisms underlying the generation and propagation of such oscillatory activity and its links with movement impairment remain partly unclear. Patients receiving deep brain stimulation of the subthalamic nucleus (STN DBS) provide a unique opportunity to address these issues by either recording the neuronal activity from the implanted electrodes or driving the network to study the behavioural and neurophysiological effects of stimulation. The studies outlined in this thesis bring further understanding into the mechanisms by which beta oscillations pervade every level of the basal ganglia – cortical network, how they impair movement and how they are modified by the usual treatments of PD such as dopamine or STN DBS. We performed a series of experiments involving PD patients either in the post-operative phase of DBS or chronically stimulated, and in an animal model of PD to study the effect of beta frequency STN stimulation on movement, the effect of high frequency STN stimulation on beta oscillations and the network properties underlying its vulnerability to beta frequencies. The findings of these studies suggest the existence of anatomically segregated subthalamo-cortical networks, with specific properties and susceptibility to resonate variably impaired in PD patients. We propose that excessive beta oscillations in PD are primarily due to a failing damping system rather than a net increase in their generation, and that dopaminergic drugs act to partially restore this damping system, while high frequency DBS suppresses pathological local beta activity. / Abstract in French: Les oscillations neuronales dans la bande beta (10-35 Hz) sont caractéristiques de la maladie de Parkinson (MP). Toutefois, les mécanismes qui sous-tendent la genèse et la propagation des ces activités et leurs liens avec les troubles moteurs restent obscurs. La chirurgie de stimulation des noyaux sous-thalamiques (NST) permet d’enregistrer l’activité neuronale par l’électrode implantée et d’étudier les effets moteurs et neurophysiologiques de la stimulation. Les travaux présentés dans cette thèse ont pour but d’améliorer la compréhension de l’origine de la diffusion des oscillations beta dans le réseau subthalamo-cortical, de leur retentissement sur la motricité et de l’influence des traitements de la MP sur celles-ci. Nous avons effectué une série d’expériences chez des patients parkinsoniens et chez un modèle animal de la MP pour étudir les effets de la stimulation du NST dans la bande beta sur la motricité, ceux de la stimulation à haute fréquence du NST sur les oscillations beta et les propriétés de réseau à l’origine de sa vulnérabilité aux fréquences beta. Les résultats de ces travaux suggèrent l’existence de réseaux subthalamo-corticaux distincts, présentant des propriétés et une susceptibilité à la résonance propres, et qui seraient atteints de façon variable selon les patients, possiblement en rapport avec la variabilité clinique de la MP. Nous proposons que les oscillations beta dans la MP sont principalement dues à la faillite du système d’atténuation plutôt qu’à une augmentation de leur genèse, que les traitements dopaminergiques restaurent partiellement ce système d’atténuation alors que la stimulation à haute fréquence du NST supprime cette activité.
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Eusebio, Alexandre. "Mechanisms and consequences of beta oscillatory activity propagation in the basal ganglia-cortical network in Parkinson's disease." Paris 6, 2011. http://www.theses.fr/2011PA066711.
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Les oscillations neuronales dans la bande beta (10-35 Hz) sont caractéristiques de la maladie de Parkinson (MP). Toutefois, les mécanismes qui sous-tendent la genèse et la propagation des ces activités et leurs liens avec les troubles moteurs restent obscurs. La chirurgie de stimulation des noyaux sous-thalamiques (NST) permet d’enregistrer l’activité neuronale par l’électrode implantée et d’étudier les effets moteurs et neurophysiologiques de la stimulation. Les travaux présentés dans cette thèse ont pour but d’améliorer la compréhension de l’origine de la diffusion des oscillations beta dans le réseau subthalamo-cortical, de leur retentissement sur la motricité et de l’influence des traitements de la MP sur celles-ci. Nous avons effectué une série d’expériences chez des patients parkinsoniens et chez un modèle animal de la MP pour étudir les effets de la stimulation du NST dans la bande beta sur la motricité, ceux de la stimulation à haute fréquence du NST sur les oscillations beta et les propriétés de réseau à l’origine de sa vulnérabilité aux fréquences beta. Les résultats de ces travaux suggèrent l’existence de réseaux subthalamo-corticaux distincts, présentant des propriétés et une susceptibilité à la résonance propres, et qui seraient atteints de façon variable selon les patients, possiblement en rapport avec la variabilité clinique de la MP. Nous proposons que les oscillations beta dans la MP sont principalement dues à la faillite du système d’atténuation plutôt qu’à une augmentation de leur genèse, que les traitements dopaminergiques restaurent partiellement ce système d’atténuation alors que la stimulation à haute fréquence du NST supprime cette activité
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Betizeau, Marion. "Molecular and cellular characterization of apical and basal progenitors in the primate developing cerebral cortex." Thesis, Lyon, École normale supérieure, 2013. http://www.theses.fr/2013ENSL0845/document.
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Le cortex cérébral primate a subi des modifications majeures pendant l'évolution qui ont permis le développement de fonctions cognitives supérieures. Un accroissement massif a eu lieu avec l'extension spécifique des couches supragranulaires et une forte expansion tangentielle. Le cortex primate ne possède pas uniquement davantage de neurones, comparé au rongeur, mais aussi des différences qualitatives. Ceci suggère des différences qualitatives pendant le développement du cortex.Une zone proliférative corticale supplémentaire a été identifiée chez le singe macaque: la zone subventriculaire externe (OSVZ) supposée être impliquée dans l'expansion du cortex primate. Mais les propriétés des précurseurs de l'OSVZ restent mal connues. Des techniques de microscopie en temps réel et d'immunofluorescence ont permis de réaliser une description exhaustive des précurseurs de l'OSVZ et de leurs propriétés chez le singe macaque.Nos résultats mettent en évidence des différences primates/rongeurs majeures. Les observations en temps réel révèlent des capacités prolifératives bien plus importantes des précurseurs. Les précurseurs primates de l'OSVZ présentent des taux de prolifération variables pendant la corticogenèse liés à la cinétique du cycle cellulaire. Nos enregistrements ont permis la génération d'une grande base de données de propriétés et lignages de précurseurs et la mise en évidence d’une diversité morphologique inattendue. 5 types ont été identifiés. Impliqués dans des lignages complexes, chaque type a la capacité de s'auto-renouveler et de générer directement des neurones. Parallèlement, nous avons développé une méthode de classification non supervisée des précurseurs corticaux. Cette technique a identifié les mêmes 5 types de précurseurs.Les résultats de cette thèse apportent de nouveaux éléments dans la compréhension des spécificités de la corticogenèse primate qui contribuent à l'expansion corticale et au développement de capacités cognitives supérieuresThe primate cerebral cortex underwent major modifications during evolution that enabled the development of high cognitive functions. A massive enlargement occurred with the specific expansion of the supra granular layers and the apparition of new frontal areas. Not only quantitative differences are found compared to the rodent but also qualitative differences. This points to potential qualitative differences in primate cortical development. An extra proliferating zone had already been identified during macaque corticogenesis: the outer subventricular zone (OSVZ). This zone is assumed to play a key role in the expansion of the primate cortex but the cellular and functional properties of OSVZ precursors remain elusive. We used quantitative long-term time-lapse video-microscopy (TLV) and immunofluorescence in and ex vivo to perform a detailed and exhaustive description of OSVZ precursor types and proliferative abilities at different stages of macaque cortical development. Our results highlight major rodent/primate differences. TLV observations revealed a much higher proliferative potential of OSVZ compared to the rodent SVZ. We report variable rates of proliferation linked to cell-cycle duration in a stage-specific manner. TLV recordings allowed the formation of a large database of primate precursor properties and lineages. This dataset unravelled an unexpectedly high diversity of OSVZ precursor morphologies. Five precursor types were identified. Involved in complex lineages, each precursor type can self-renew and directly generate neurons. In a parallel approach, we developed an unbiased clustering tool to automatically classify cortical precursors. This technique returned the same five precursor types as the morphological categorization. The results of this PhD thesis provide new insights into primate specificities during corticogenesis that contribute to cortical expansion and to the development of higher cognitive abilities
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Creisson, Éric. "Etude des desordres moteurs rencontres au cours de la degenerescence cortico-basale : de l'apraxie au syndrome extrapyramidal." Dijon, 1994. http://www.theses.fr/1994DIJOM056.
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Katsumi, Yukinori. "Cholinergic projection from the basal forebrain and cerebral cortical glucose metabolism in rats. An animal positron emission tomography study." Kyoto University, 2000. http://hdl.handle.net/2433/180833.
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Barbelivien, Alexandra. "Modulation du systeme cholinergique basalo-cortical vasodilatateur par la galanine : etudes cerebrovasculaires, metaboliques et neurochimiques." Caen, 1997. http://www.theses.fr/1997CAEN2027.
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Le systeme cholinergique basalo-cortical, qui lie la substantia innominata (si) au cortex cerebral et qui est implique dans la modulation du debit sanguin cerebral (dsc) subit l'influence d'autres neurotransmetteurs dont la galanine, modulateur que nous avons etudie dans cette these. En accord avec la distribution des neurones et recepteurs galaninergiques, nous avons fait l'hypothese qu'une telle interaction pouvait avoir lieu au niveau : 1) des neurones cholinergiques de la si, 2) des terminaisons cholinergiques corticales ou 3) des microvaisseaux intraparenchymateux. Dans le but d'etudier cette interaction au niveau de la si, nous avons mis au point une stimulation specifique du systeme cholinergique basalo-cortical, par injection locale de carbachol, et nous nous sommes attaches a valider ce nouveau modele et a etudier l'hypothese d'une modulation de ce systeme par la galanine. Nos resultats demontrent que notre modele semble plus adapte que la stimulation neurochimique glutamatergique pour etudier les modulateurs du systeme cholinergique basalo-cortical vasodilatateur. L'injection de carbachol dans la si entraine des augmentations du dsc dans les zones de projections de cette structure ; augmentations qui ne sont pas le reflet de variations de l'activite metabolique locale et qui sont associees a des augmentations de la liberation d'acetylcholine. Nous avons mis en evidence que la galanine exercait une modulation inhibitrice sur le systeme cholinergique basalo-cortical, au moins au niveau de la si. En effet, la galanine injectee localement, bien que depourvue d'action intrinseque sur le debit et la consommation de glucose, inhibe les augmentations de dsc induites par le carbachol. Ainsi, l'effet de la galanine sur le systeme cholinergique basalo-cortical n'est pas le reflet d'une inhibition de l'activite metabolique locale ; son action modulatrice pourrait etre liee a une inhibition des mecanismes sous-tendant l'activation des neurones cholinergique de la si.
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Cape, Edmund G. "Role of cholinergic basal forebrain neurons in the modulation of cortical activity across the sleep-waking cycle : a pharmacological study." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36796.
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Serving as the extra-thalamic relay from the ascending reticular activating system to the cerebral cortex, basal forebrain neurons and particularly the cholinergic neurons therein, are believed to play an important role in cortical activation that occurs during waking and paradoxical sleep (PS). However, basal forebrain neurons are also thought to be involved in slow wave sleep (SWS), and thus accordingly influence cortical activity in different ways across the sleep-waking cycle. The present research aimed to elucidate the way the basal forebrain modulates cortical activity and sleep-wake states in response to the different neurotransmitters contained in its brainstem afferents. Microinjections of chemicals into the basal forebrain of rats were performed using a remotely controlled apparatus that allowed study of electroencephalographic (EEG) and behavioral changes without disturbing the rat's normal sleep-waking cycle. In a first study using spectral analysis of the EEG, it was established that high frequency gamma (30--60 Hz) activity reflects cortical activation and behavioral arousal during waking and PS and that gamma varies reciprocally with delta (1--4 Hz) and positively with theta (4--8 Hz) across these states. Noradrenaline, which excites cholinergic neurons to discharge in a tonic mode and has differential effects on non-cholinergic neurons, increased gamma and decreased delta EEG activities while eliciting waking. The glutamate agonist, AMPA, produced similar effects, and NMDA, which is known to induce a bursting discharge in cholinergic neurons, additionally increased theta activity in association with an active waking state. Moreover, neurotensin, which acts selectively to excite cholinergic cells to discharge in a bursting mode, evoked gamma and theta while enhancing both waking and PS in the provoked absence of SWS. In contrast, serotonin, which inhibits cholinergic neurons and has minimal effects on non-cholinergic neurons, decreased gamma and th
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Aiello, Kiara [Verfasser], Jürgen [Akademischer Betreuer] Bolz, Dominique [Akademischer Betreuer] Bagnard, and Valerie [Akademischer Betreuer] Castellani. "Semaphorin 3C guides MGE-derived cortical interneurons through the basal telencephalon / Kiara Aiello. Gutachter: Jürgen Bolz ; Dominique Bagnard ; Valerie Castellani." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2015. http://d-nb.info/1069532401/34.
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St, Hilaire Melissa April. "How sleep deprivation degrades task performance: combining experimental analysis with simulations of adenosinergic effects of basal ganglia and cortical circuits." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12852.
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Thesis (Ph.D.)--Boston UniversityHumans configure themselves into "neural machines" to perform optimally on distinct tasks, and they excel at maintaining such configurations for brief episodes. The neural configuration needed for peak performance, however, is subject to perturbations on multiple time scales. This thesis reports new empirical analyses and computational modeling to advance understanding of the variations in reaction time (RT) on simple RT tasks that are associated with the duration of the preceding inter-stimulus interval (order of seconds); the time-on-task duration (order of minutes); and sleep deprivation duration (order of hours to days). Responses from the psychomotor vigilance task (PVT), including anticipations (false alarms), normal RTs, and very long RTs (lapses in attention), were analyzed to discover the effects of: the 1 - 9 second inter-stimulus interval (ISI); the 10-minute task session; up to 50 hours of sleep deprivation (SD); and wake-promoting agents, caffeine and modafinil. Normal RTs and lapses in attention were negatively correlated with ISI length, whereas anticipations were positively correlated. Anticipations, normal RTs, and lapses increased as time-on-task increased, and during SD. Both caffeine and modafinil reduced lapses and anticipations during SD and decreased RT variability. A simple neural network model incorporating both a time-dependent inhibitory process and a time-dependent excitatory process was developed. The model robustly simulated the ISI effect on behavior. The SD effects were reproducible with two parameter adjustments. Informed modeling of drug effects required greater neurobiological detail. In the basal ganglia (BG), adenosine accumulation during SD has two notable effects: it antagonizes dopamine to reduce BG responsiveness to incoming cortical signals, and it reduces cholinergic transmission to parietal and prefrontal cortices, thus reducing attention to visual signals. A detailed computational model of interactions between BG and cortex during PVT was developed to simulate effects of adenosine and their amelioration by caffeine. The model simulates drug, ISI and SD effects on anticipations, RTs, and lapses. This model can be used to describe the effects of SD over a wide range of tasks requiring planned and reactive movements, and can predict and model effects of pharmacological agents acting on the adenosinergic, cholinergic and dopaminergic systems.
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Nelson, Christopher L. "Prefrontal cortical modulation of posterior parietal acetylcholine release a study of glutamatergic and cholinergic mechanisms /." Connect to this title online, 2004. http://rave.ohiolink.etd/etdc/view?acc%5Fnum=osu1069868437.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xi, 130 p.; also includes graphics (some col.). Includes bibliographical references (p. 109-130). Available online via OhioLINK's ETD Center
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Ballan, Guillaume. "La dégénérescence cortico-basale : analyse de la littérature et étude personnelle à propos de 15 cas." Bordeaux 2, 1996. http://www.theses.fr/1996BOR23061.
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Lehmann, Olivia. "Systèmes cholinergiques septo-hippocampique et basalo-cortical : Implication dans las fonctions mnésiques et attentionnelles, et modulation sérotoninergique." Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13126.
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Ce travail a consisté à préciser les implications des systèmes cholinergiques basalo-cortical et septo-hippocampique et des voies sérotoninergiques ascendantes dans certaines fonctions cognitives (mémoire spatiale, attention) chez le Rat. A cette fin, nous nous sommes basés sur une approche originale associant l'injection intracérébrale de deux neurotoxines présentant une bonne sélectivité neurochimique, la 192IgG-saporine et la 5,7-DHT. Nos travaux ont permis de mettre en évidence qu'une lésion inframaximale mais générale des systèmes cholinergiques ou sérotoninergiques centraux, afférants au cortex et à l' hippocampe, n'induit que peu d'effets par elle-même, alors que la combinaison des deux lésions fait apparaître des déficits de mémoire spatiale de travail, ainsi qu'une hyperactivité locomotrice. A l'inverse, lorsque seules les afférences cholinergiques septo-hippocampiques sont lésées, on constate des déficits de mémoire spatiale de travail qui sont atténués par une dénervation sérotoninergique de l'hippocampe. Une étude pharmacologique indique une éventuelle implication d'un mécanisme basé sur des récepteurs 5-HT1A hippocampiques dans cet effet. Enfin, nous avons clairement montré que la lésion sélective des neurones basalo-corticaux provoque des déficits attentionnels sans affecter la mémoire spatiale de travail, alors que la lésion des neurones septo-hippocampiques perturbe gravement la mémoire spatiale de travail, sans toucher aux performances attentionnelles. Dans leur ensemble, ces résultats montrent i) que les systèmes cholinergiques septo-hippocampique et basalo-cortical ont des implications cognitives fortes, mais bien distinctes, le premier intervenant dans la mémoire spatiale de travail quand le second intervient dans l'attention sélective et ii) qu'une partie des fonctions mnésiques étudiées implique une modulation sérotoninergiqueThe experiments presented herein aimed at clarifying the cognitive implications of the basalocortical and septohippocampal cholinergic systems, and of the ascending serotonergic projections in cognitive functions (spatial memory, attention) in rats. Most experiments relied upon the association of intracerebral injections of neurotoxins having excellent neurochemical selectivity, namely 192 IgG-saporin and 5,7-dihydroxytrypatmine. We showed that submaximal but general lesions of the basal forebrain cholinergic neurons or of the serotonergic fibers arising from the raphé had weak or no effects, while the combination of both lesions altered spatial memory and induced hyperlocomotion. When only the cholinergic afferents of the hippocampus underwent extensive damage, spatial working memory deficits were dramatic, but they could be attenuated by a serotonergic denervation of the hippocampus. A pharmacological approach indicated that 5-HT1A receptors might be involved in this attenuation. Finally, we have demonstrated that selective cholinergic lesions in the septal area induced spatial memory deficits but had no effect on attention, whereas selective cholinergic lesions of the nucleus basalis magnocellularis had no effect on spatial memory but dramatically altered attention. Altogether, these results show i) that the septohippocampal and basalocortical cholinergic systems have cognitive implications, which are strong but different, the basalocortical one being involved in attention and the septohippocampal one in spatial working memory ii) that part of the mnemonic functions assessed involve a serotonergic modulation
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Henny, V. Pablo. "Ascending and descending projections of cholinergic, GABAergic and glutamatergic basal forebrain neurons and their role in cortical activity and sleep-wake states." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103162.
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The basal forebrain (BF) plays multiple and divergent roles in the modulation of cortical activity and the control of sleep-wake states. BF neurons project to cortex, where they promote cortical activation during wakefulness (W) and paradoxical sleep (PS). Other neurons may conversely promote the appearance of slow wave activity (SWA) that occurs during slow wave sleep (SWS). BF neurons also send projections to the lateral hypothalamus (LH), a wake- and arousal-promoting region and whose inhibition by the BF is thought to facilitate the appearance of behavioral quiescence and sleep. It is likely that these multiple roles are carried out by the heterogeneous population that comprises the BF, which include cholinergic, GABAergic and as yet putative glutamatergic neurons which, as shown by retrograde tracing, innervate these areas. To better understand the mechanisms through which BF neurons modulate cortical activity and sleep-wake states, research was carried out to determine the numbers of cholinergic, GABAergic and putative glutamatergic neurons in the BF, and to examine their respective efferent projections to the cortex and LH. Following stereological quantification of immunohistochemically identified ACh-, GABA- and glutamate-synthesizing neurons, anterograde transport of biotinylated dextran amine 10,000 MW (BDA) in magnocellular BF neurons was combined with immunohistochemistry for vesicular transporter proteins (VTPs) for ACh (VAChT), GABA (VGAT) or glutamate (VGIuT) for identification of BF terminals in prefrontal cortex (PFC) and LH. Subsequent stereological analysis was used to determine contributions of cholinergic, GABAergic and newly identify glutamatergic BF axon terminals to these areas. There, triple fluorescent staining was performed to describe the innervation by BF terminals of pyramidal and interneuronal cell groups in the PFC and of the orexin/hypocretin cell population in the LH. Additional triple staining with postsynaptic markers was used to provide evidence for synaptic contacts. Together, these findings demonstrate the existence of at least three neuronal contingents of BF neurons, which may have the capacity to modulate the activity of cortical or LH neurons and thus, to control different aspects of cortical activity and sleep-wake states.
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FAYET, GUILLEMETTE. "La degenerescence corticobasale : a propos de 3 observations avec etude en tomographie par emission monophotonique (spect) au 99mtchmpao : frontiere nosologique avec les atrophies focales progressives." Nantes, 1994. http://www.theses.fr/1994NANT266M.
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Froux, Lionel. "Propriétés de la synapse cortico-sous-thalamique : étude optogénétique chez le rongeur." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0208/document.
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Les ganglions de la base (GB) forment un réseau de structures sous-corticales impliquées dans la motricité volontaire, mais aussi dans des aspects plus cognitifs et motivationnels du comportement moteur. La dopamine est un neuromodulateur essentiel au bon fonctionnement de ce réseau. La synapse cortico-sous-thalamique (cortico-NST) est une synapse glutamatergique (excitatrice) transmettant les informations corticales au noyau sous-thalamique (NST), ce qui forme la première partie d’une des trois voies des GB : la voie hyperdirecte. La voie cortico-NST est impliquée dans des tâches de type « go-no-go » (arrêt d’un acte moteur débuté) et dans les effets bénéfiques de la stimulation cérébrale profonde du NST sur les symptômes de la maladie de Parkinson. Cependant, les propriétés des synapses cortico-NST ne sont pas connues. Ce manque d’informations provient, en partie, de l’anatomie particulière de cette voie, qui rend l’étude in vitro de la synapse cortico-NST difficile. L’utilisation de l’optogénétique nous a permis de contourner ce problème. En associant cette technique à l’électrophysiologie sur tranches de cerveaux de rongeur, nous avons mis en évidence un effet inhibiteur des récepteurs dopaminergiques D5 sur la transmission cortico-NST. Nous montrons également que les propriétés de plasticité à court terme de cette synapse lui permettent de réduire l’influence des messages corticaux à haute fréquence sur le NST. Les résultats obtenus au cours de cette thèse montrent que l’optogénétique est un bon moyen d’étudier la synapse cortico-NST in vitro et contribuent à améliorer la compréhension des propriétés de la cette synapseBasal ganglia (BG) are a group of subcortical nuclei involved in action selection and in cognitive and motivational aspects of motor behavior. Dopamine is essential for proper functioning of BG. The cortico-subthalamic (cortico-STN) synapse is a glutamatergic (excitatory) synapse involved in signal transmission from cortex to subthalamic nucleus (STN). The cortico-STN synapse is the first synapse in the hyperdirect pathway, one of the three pathways of BG. Even if the cortico-STN pathway is involved in “go-no-go” tasks (stopping of an already started motor act) and in the beneficial effects of the high frequency stimulation of the STN on Parkinsonian symptoms, properties of the cortico-STN synapse are not well described. The lack of data is due, at least in part, to the specific anatomy of the cortico-STN pathway which does not allow the use of standard methods in vitro. The use of optogenetics allowed us to circumvent this issue. By coupling this approach with electrophysiology on brain slices in rodents, we show that dopaminergic D5 receptors stimulation reduces glutamatergic transmission at cortico-STN synapses. We also show that short-term plasticity properties of this synapse reduce the influence of high frequency cortical inputs on the STN. Our findings indicate that optogenetics enables studying the cortico-STN synapse in vitro and contributes to improving our knowledge of the properties of the synapse
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Shimotake, Akihiro. "Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes." Kyoto University, 2015. http://hdl.handle.net/2433/202675.
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Mendes, Alexandre. "Homo- et hétérosynaptique spike-timing-dependent plasticity aux synapses cortico- et thalamo-striatales." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066432/document.
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D’après le postulat de Hebb, les circuits neuronaux ajustent et modifient durablement leurs poids synaptiques en fonction des patrons de décharges de part et d’autre de la synapse. La « spike-timing-dependent plasticity » (STDP) est une règle d’apprentissage synaptique hebbienne dépendante de la séquence temporelle précise (de l’ordre de la milliseconde) des activités appariées des neurones pré- et post-synaptiques. Le striatum, le principal noyau d’entrée des ganglions de la base, reçoit des afférences excitatrices provenant du cortex cérébral et du thalamus dont les activités peuvent être concomitantes ou décalées dans le temps. Ainsi, l’encodage temporal des informations corticales et thalamiques via la STDP pourrait être crucial pour l’implication du striatum dans l’apprentissage procédural. Nous avons exploré les plasticités synaptiques cortico- et thalamo-striatales puis leurs interactions à travers le paradigme de la STDP. Les principaux résultats sont :1. Les « spike-timing-dependent plasticity » opposées cortico-striatales et thalamo-striatales induisent des plasticités hétérosynaptiques. Si la très grande majorité des études sont consacrées à la plasticité synaptique cortico-striatale, peu ont exploré les règles de plasticité synaptique aux synapses thalamo-striatale et leurs interactions avec la plasticité cortico-striatale. Nous avons étudié la STDP thalamo-striatale et comment les plasticités synaptiques thalamo- et cortico-striatales interagissent…According to Hebbian postulate, neural circuits tune their synaptic weights depending on patterned firing of action potential on either side of the synapse. Spike-timing-dependent plasticity (STDP) is an experimental implementation of Hebbian plasticity that relies on the precise order and the millisecond timing of the paired activities in pre- and postsynaptic neurons. The striatum, the primary entrance to basal ganglia, integrates excitatory inputs from both cerebral cortex and thalamus whose activities can be concomitant or delayed. Thus, temporal coding of cortical and thalamic information via STDP paradigm may be crucial for the role of the striatum in procedural learning. Here, we explored cortico-striatal and thalamo-striatal synaptic plasticity and their interplay through STDP paradigm. The main results described here are:1. Opposing spike-timing dependent plasticity at cortical and thalamic inputs drive heterosynaptic plasticity in striatumIf the vast majority of the studies focused on cortico-striatal synaptic plasticity, much less is known about thalamo-striatal plasticity rules and their interplay with cortico-striatal plasticity. Here, we explored thalamo-striatal STDP and how thalamo-striatal and cortico-striatal synaptic plasticity interplay. a) While bidirectional and anti-Hebbian STDP was observed at cortico-striatal synapses, thalamo-striatal exhibited bidirectional and hebbian STDP
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Bellot, Jean. "Modélisation computationnelle du rôle de la dopamine dans les boucles cortico-striatales dans l'apprentissage et la régulation de la sélection de l'action." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066257/document.
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Dans ce travail de thèse, nous avons modélisé le rôle de la dopamine dans l'apprentissage et dans les processus de sélection de l'action en lien avec les ganglions de la base. L'activité des neurones dopaminergiques présente de nombreuses similarités avec l'erreur de prédiction de la récompense utilisée par les algorithmes d'apprentissage par renforcement. Ainsi, ces neurones sont supposés guider le processus de sélection de l'action.Dans une première partie, nous avons analysé l'information encodée par les neurones dopaminergiques dans une tâche à choix multiples en la comparant à différentes informations utilisées par les modèles d'apprentissage par renforcement. Nos résultats suggèrent que l'information encodée par les neurones dopaminergiques enregistrer dans la tâche n'est que partiellement compatible avec une erreur de prédiction et semble en partie dissociée du comportement.Dans une deuxième partie, nous avons simulé l'effet de la dopamine sur un modèle des ganglions de la base prenant en compte des connections existant chez le primate, souvent négligées dans la littérature. La plupart des modèles actuels font en effet l'hypothèse d'une séparation stricte de deux chemins dans les ganglions de la base : le chemin direct lié à la récompense et le chemin indirect lié à la punition. Cependant des études anatomiques remettent en question cette dissociation, en particulier chez le primate. Nous proposons ainsi d'étudier comment différents niveaux de dopamine, dans le contexte de la maladie de Parkinson, affectent l'apprentissage et la sélection de l'action dans ce modèleIn this thesis work, we modelled the role of dopamine in learning and in the processes of action selection through its interaction with the basal ganglia. During the 90’s, the work of Schultz and colleagues has led to major progress in understanding the neural mechanisms underlying the influence of feedback on learning. The activity of dopaminergic neurons exhibited properties of the reward prediction error signal used in so-called Temporal Difference (TD) machine learning algorithms. Thus, DA has been thought to be the neural signal that help us to adapt our behavior. In the first part of my PhD, we analyze the information encoded by dopaminergic neurons recorded during a multi-choice task. In this purpose, we modeled the task and simulated different TD learning algorithms to quantitatively compare their ability to reproduce dopamine neurons activity. Our results show that the information carried out by dopamine neurons is only partly consistent with a reward prediction error and seems to be dissociated from behavioral adaptation.In the second part of my PhD, we study the effect of different levels of dopamine in a biologically plausible model of primates basal ganglia that considers existing connections often neglected in the literature. Indeed, most of current models of basal ganglia assume the existence of two segregated pathway: the direct pathway associated with reward and the indirect pathway associated with punishment. However, anatomical studies in primates revealed that these two pathways are not dissociated. We study the ability of such a model to reproduce beta oscillations observed in Parkinsonian and the differences in reward and punishment sensitivity, with high or low-level of dopamine
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Marchalant, Yannick. "Interactions physiopathologiques entre système galaninergique et système cholinergique basalo-cortical : influence fonctionnelle sur les relations entre activité neuronale, métabolisme et débit sanguin cérébral chez le rongeur." Caen, 2004. http://www.theses.fr/2004CAEN2008.
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Sur la base de données physiologiques et physiopathologiques, nous avons étudié l'implication du système galaninergique et du système cholinergique basalo-cortical sur la régulation de la perfusion corticale. Dans un premier travail d'immunocytochimie couplée à la microscopie optique, confocale et électronique, nous avons démontré l'existence d'une innervation galaninergique des vaisseaux intracorticaux chez le rat sain. Dans une deuxième approche de physiopathologie expérimentale, nous avons reproduit la lésion des corps cellulaires cholinergiques du nucleus basalis magnocellularis (nbm) par lésion sélective directe (192-IgG-saporine) ou rétrograde à partir du cortex cérébral (ischémie corticale contrôlée). L'intensité de l'innervation galaninergique cérébrovasculaire a été réduite par la lésion directe du nbm. A l'inverse, la lésion rétrograde à partir du cortex, a induit une hyperinnervation galaninergique du nbm. Cette hyperinnervation, reproduite expérimentalement par injection locale de galanine, induit une modulation inhibitrice du système cholinergique basalo-cortical et de ses fonctions neurochimiques et vasculaires. Une troisième approche expérimentale fonctionnelle nous a permis de démontrer que cette voie cholinergique est impliquée dans les mécanismes de couplage neurovasculaire en condition d'activation somatosensorielle. L'ensemble de notre travail démontre le rôle primordial de la voie cholinergique provenant du nbm dans les mécanismes d'activation corticale et les implications majeures du système galaninergique en conditions d'altérations physiopathologiques, telles que celles retrouvées au cours de la maladie d'Alzheimer.
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Narayanan, Ramanathan [Verfasser], Jochen [Akademischer Betreuer] Staiger, André [Gutachter] Fischer, and Klaus-Armin [Gutachter] Nave. "BAF155 regulates the genesis of basal progenitors through both Pax6-dependent and independent mechanisms during cerebral cortex development : Role of BAF155 and PAX6 in cortical development / Ramanathan Narayanan ; Gutachter: André Fischer, Klaus-Armin Nave ; Betreuer: Jochen Staiger." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2018. http://d-nb.info/115600828X/34.
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Badreddine, Nagham. "Caractérisation des substrats neuronaux de la mémoire procédurale : rôle de la dynamique des réseaux corticostriataux Spatiotemporal reorganization of corticostriatal network 1 dynamics encodes 2 motor skill learning." Thesis, Université Grenoble Alpes, 2020. https://thares.univ-grenoble-alpes.fr/2020GRALV032.pdf.
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La mémoire procédurale est la mémoire des habitudes motrices. Les ganglions de la base (GB), un groupe de structures impliqué dans les fonctions motrices et cognitives, sont responsables de la formation de cette mémoire. Le striatum, principale structure d’entrée des GB, joue un rôle central dans le transfert de l’information entre le cortex et les autres structures sous-corticales, assurant ainsi la sélection et l’intégration de l’information corticale au sein de boucles fonctionnelles parallèles. Lors d’un apprentissage procédural, le comportement est tout d’abord dirigé vers un but, impliquant les boucles associatives et le striatum dorsomédial (DMS), pour ensuite évoluer vers un comportement habituel automatique, impliquant les boucles sensorimotrices et le striatum dorsolatéral (DLS). L’anatomie des circuits et la dynamique des réseaux striataux au cours de l’apprentissage procédural ont été bien décrites. Cependant, comment la mémoire procédurale est précisément encodée au niveau des réseaux corticostriataux (CS) reste inconnu.Dans mon travail de thèse, nous nous sommes intéressés à la caractérisation des dynamiques des réseaux CS impliqués dans l’apprentissage procédural et nous avons exploré l’existence de substrats neuronaux responsables de la formation de cette mémoire. Grâce à l’imagerie calcique ex vivo nous avons monitoré l’activité des réseaux CS durant les différentes phases d’apprentissage. Nous avons extrait et analysé les signaux calciques des neurones épineux moyens (MSN), les neurones de sortie du striatum. Afin de distinguer les MSNs des autres neurones striataux, nous avons développé un classifieur basé sur les réponses calciques des neurones et leur morphologie. Nous avons montré qu’il existe une réorganisation spécifique des réseaux DMS pendant la 1ère phase d’apprentissage moteur. L’activité dans le DMS est diminuée après un entraînement léger, avec une forte activité (HA) maintenue dans un petit groupe de cellules, et retournant à un niveau basal après un entrainement intense. Dans le DLS, la réorganisation est graduelle et localisée dans des ‘clusters’ d’activité (HA) après un entrainement intense. L’existence des cellules et clusters HA est directement corrélée à la qualité de l’apprentissage. Nous avons ensuite exploré les mécanismes sous-tendant cette réorganisation. Grâce à des enregistrements en patch-clamp nous avons examiné les propriétés des cellules et clusters HA et montré une augmentation du poids synaptique des afférences du cortex cingulaire sur les cellules HA dans le DMS après un entrainement léger. Des études de traçage anatomique ont montré des changements plus robustes dans le DLS avec une augmentation du nombre de projections du cortex somatosensoriel après entrainement intense. Une stratégie cFos-TRAP couplée à la chimiogénétique nous a permis d’inhiber spécifiquement les cellules et clusters HA, et montrer que cela affecte l’apprentissage moteur. Ceci montre la nécessité de ces cellules dans les premières et dernières phases de l’apprentissage moteur respectivement.Ensuite, notre but était d’explorer s’il existe des déficits d’apprentissage moteur dans une phase présymptomatique dans un modèle murin de la maladie de Huntington, et d’examiner l’association de ces déficits à des altérations au niveau des réseaux CS. Nous avons d’abord montré qu’il existait des déficits dans la dernière phase d’apprentissage dans ce modèle murin. Grâce à l’imagerie calcique ex vivo, nous avons observé une altération des réseaux du DMS et du DLS dans des conditions naïve ainsi qu’une absence de réorganisation des réseaux après l’apprentissage. Ainsi, ces résultats confirment l’importance de la réorganisation des réseaux pour l’apprentissage moteur.L’ensemble de ce travail offre de nouvelles perspectives quant au rôle des réseaux CS et leur réorganisation dans l’apprentissage moteur. La nécessité des cellules HA et des clusters ouvrent les portes du monde de l’engramme dans les réseaux striatauxProcedural memory is the memory of habits, involved in the acquisition and maintenance of new motor skills. The neural substrates underlying this memory are the basal ganglia (BG), a group of structures involved in motor and cognitive functions. The input nucleus of the BG is the striatum, earning it a central role in relaying information between the cortex and other subcortical structures, thus ensuring the selection and integration of cortical information within parallel functional loops. Procedural learning first follows a goal-directed behavior mediated by the associative loops, including the dorsomedial striatum (DMS), which is then transferred to an automatic behavior where habit is formed and mediated by the sensorimotor loops including the dorsolateral striatum (DLS). The anatomy and the evolution of the dynamics of the striatal networks has been well described during procedural learning, and the involvement of each striatal territory in a specific phase of learning established. However, how procedural learning is encoded at the level of the corticostriatal networks remains unknown.During my PhD work, we were interested in characterizing the dynamics of the corticostriatal networks involved in motor skill learning and determining the neural correlates responsible for the formation of this memory. We first used two-photon ex vivo calcium imaging to monitor the activity of the networks during the different phases of procedural learning. First we extracted the calcium responses of only medium spiny neurons (MSNs), the striatal output neurons. To distinguish MSNs from other striatal neurons, we developed a cell-sorting classifier based on the calcium responses of neurons and their morphology. We showed a specific reorganization of the DMS networks during the early phase, and the DLS during the late phase of motor skill learning. In DMS, the activity of the networks decreased after early training and returned to a basal level after late training. The main activity of the DMS networks was held by a group of highly active (HA) cells. In DLS, the reorganization of the activity was gradual and localized in small clusters of activity after late training. We then examined the properties of the HA cells in DMS and clusters in DLS. The existence of HA cells and clusters are directly correlated to the performance of the animals. Whole-cell patch-clamp recordings allowed us to characterize electrophysiological properties of HA bells and determine an increase of the synaptic weight of cingulate cortex inputs to HA cells in DMS after early learning. Anatomical tracing showed more robust changes in the DLS with an increase of the number of somatosensory projections to the DLS after late training. Using an AAV cFos-TRAP strategy coupled to chemogenetics, we inhibited HA and cluster cells, leading to impaired motor learning. These experiments thus highlighted the necessity of these cells in early and late phases of motor skill learning respectively.Next we wanted to explore if deficits in motor skill learning occur in a premotor-symptomatic phase of a mouse model of Huntington’s disease (HD), and if they would be associated to dysfunctions in the corticostriatal networks. We first showed deficits in the late phase of motor skill learning in a mouse model of HD. Using ex vivo two-photon calcium imaging, we explored the DMS and DLS networks and we observed an alteration of both networks in naïve HD animals and in addition, an absence of reorganization upon motor skill learning. These results confirm the importance of the reorganization of the networks in motor skill learning.Altogether, this work provides a new insight on the role of the corticostriatal networks and their reorganization in motor skill learning. The necessity of HA and cluster cells opens the door of the ‘engram’ world to the striatal networks
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Thurnham, A. J. "Computational modelling of the neural systems involved in schizophrenia." Thesis, University of Hertfordshire, 2008. http://hdl.handle.net/2299/1842.
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The aim of this thesis is to improve our understanding of the neural systems involved in schizophrenia by suggesting possible avenues for future computational modelling in an attempt to make sense of the vast number of studies relating to the symptoms and cognitive deficits relating to the disorder. This multidisciplinary research has covered three different levels of analysis: abnormalities in the microscopic brain structure, dopamine dysfunction at a neurochemical level, and interactions between cortical and subcortical brain areas, connected by cortico-basal ganglia circuit loops; and has culminated in the production of five models that provide useful clarification in this difficult field. My thesis comprises three major relevant modelling themes. Firstly, in Chapter 3 I looked at an existing neural network model addressing the Neurodevelopmental Hypothesis of Schizophrenia by Hoffman and McGlashan (1997). However, it soon became clear that such models were overly simplistic and brittle when it came to replication. While they focused on hallucinations and connectivity in the frontal lobes they ignored other symptoms and the evidence of reductions in volume of the temporal lobes in schizophrenia. No mention was made of the considerable evidence of dysfunction of the dopamine system and associated areas, such as the basal ganglia. This led to my second line of reasoning: dopamine dysfunction. Initially I helped create a novel model of dopamine neuron firing based on the Computational Substrate for Incentive Salience by McClure, Daw and Montague (2003), incorporating temporal difference (TD) reward prediction errors (Chapter 5). I adapted this model in Chapter 6 to address the ongoing debate as to whether or not dopamine encodes uncertainty in the delay period between presentation of a conditioned stimulus and receipt of a reward, as demonstrated by sustained activation seen in single dopamine neuron recordings (Fiorillo, Tobler & Schultz 2003). An answer to this question could result in a better understanding of the nature of dopamine signaling, with implications for the psychopathology of cognitive disorders, like schizophrenia, for which dopamine is commonly regarded as having a primary role. Computational modelling enabled me to suggest that while sustained activation is common in single trials, there is the possibility that it increases with increasing probability, in which case dopamine may not be encoding uncertainty in this manner. Importantly, these predictions can be tested and verified by experimental data. My third modelling theme arose as a result of the limitations to using TD alone to account for a reinforcement learning account of action control in the brain. In Chapter 8 I introduce a dual weighted artificial neural network, originally designed by Hinton and Plaut (1987) to address the problem of catastrophic forgetting in multilayer artificial neural networks. I suggest an alternative use for a model with fast and slow weights to address the problem of arbitration between two systems of control. This novel approach is capable of combining the benefits of model free and model based learning in one simple model, without need for a homunculus and may have important implications in addressing how both goal directed and stimulus response learning may coexist. Modelling cortical-subcortical loops offers the potential of incorporating both the symptoms and cognitive deficits associated with schizophrenia by taking into account the interactions between midbrain/striatum and cortical areas.
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Reinel, Claudia. "Multidisziplinäre Untersuchung dopaminerger Mechanismen der repetitiven Störungen anhand von zwei Rattenmodellen dopaminerger Dysregulation." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17390.
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Repetitive Störungen manifestieren sich als Leitsymptom in der Zwangsstörung und dem Tourette-Syndrom. Die Symptome werden als enthemmte Stereotypien eines desinhibierten Basalganglien-thalamo-kortikalen (BGTC) Regelkreises verstanden. Überdies wird als neurochemisches Korrelat ein dysregulatives Dopamin (DA)-System innerhalb dieser Kerngebiete nahegelegt, welches über ein überaktives Dopamintransporter (DAT)-System erklärt werden könnte. In der Induktion repetitiver Erkrankungen ist die Interaktion des BGTC Regelkreises und des DA-Systems dennoch unklar. In der vorliegenden Arbeit wurden daher anhand von zwei Pathologiemodellen (Ratte) mit unterschiedlich induzierter Dysregulation des DA-Systems (transgen versus pharmakologisch) die dysfunktionalen Einheiten im BGTC Regelkreises vergleichend untersucht. Im transgenen Modell führte die zentralnervöse DAT-Überexpression: (1) zu einer verstärkten Genexpression des vesikulären Monoamintransporter 2 (VMAT2) sowie des DA-Rezeptors 1 und DA–Rezeptors 2 (DRD1, DRD2), (2) zu einem reduzierten DA-Spiegel mit erhöhter DA-Umsatzrate und veränderten serotonergen- und GABAergen-System, und (3) zu perserverativen Verhalten. Im Gegensatz dazu zeigte die chronische Applikation mit dem D2-Agonisten Quinpirol im pharmakologischen Modell: (1) eine Reduktion des DAT, VMAT2 und DRD2, (2) eine reduzierte DA-Umsatzrate und (3) zwanghaftes Kontrollverhalten. Die Ergebnisse legen nahe, dass die unterschiedlichen klinischen Subtypen der Zwangsstörung unterschiedlichen neurobiologischen Veränderungen zugrunde liegen könnten. Ferner bietet das hier vorgestellte transgene Modell erfolgsversprechende Ansatzpunkte um als neues valides Tiermodell der repetitiven Störungen etabliert zu werden.Repetitive disorders manifest as the cardinal symptom in obsessive-compulsive disorder and Tourette syndrome. The symptoms are understood as disinhibited stereotypies of a basal ganglia-thalamo-cortical (BGTC) circuit. Furthermore, it is suggested that a dysregulated dopamine (DA) system within this circuit is the underlying neurochemical correlate which could be explained by an overactive dopamine transporter (DAT). At this point, it is still unclear how the BGTC circuit and the DA system interact in the induction of repetitive disorders. Therefore we investigated the dysfunctional unities within the BGTC circuit by comparing two pathological rat models (transgenic versus pharmacologic) with different induced dopaminergic dysregulation. The DAT overexpressing rat model showed: (1) increased gene expression of the vesicular monoamine transporter 2 (VMAT2), DA receptor D1 (DRD1) and DA receptor D2 (DRD2), (2) lower levels of DA with an increased DA metabolism and alterations in the serotonin- and GABA system, and (3) perseverative behavior. In contrast, the chronic application of the D2 receptor agonist quinpirole resulted in the pharmacologic model in: (1) lower gene expressions of the DAT, VMAT2 and DRD2, (2) reduced DA-turnover and (3) compulsive control behavior. These results suggest that different clinical subtypes of obsessive-compulsive disorder caused by different neurobiological alterations. In addition, the presented transgenic model provides the opportunity to be established as a new valid animal model of repetitive disorders.
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Menneh, Rosalyn. "Prediction of the clinical response to psychostimulant by the basal and reactive salivary cortisol in children with ADHD." Thèse, 2008. http://hdl.handle.net/1866/2701.
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Le trouble du déficit de l’attention/hyperactivité (TDA/H) est un des troubles
comportementaux le plus commun chez les enfants. TDAH a une étiologie complexe et des
traitements efficaces. Le médicament le plus prescrit est le méthylphénidate, un
psychostimulant qui bloque le transporteur de la dopamine et augmente la disponibilité de
la dopamine dans la fente synaptique. Des études précliniques et cliniques suggèrent que le
cortisol peut potentialiser les effets de la dopamine. Un dysfonctionnement du système
hypothalamo-hypophyso-surrénalien (HHS) est associé avec plusieurs maladies
psychiatriques comme la dépression, le trouble bipolaire, et l’anxiété. Nous avons fait
l’hypothèse que le cortisol influence l’efficacité du traitement des symptômes du TDAH
par le méthylphénidate.
L’objectif de cette étude est de mesurer les niveaux de cortisol le matin au réveil et
en réponse à une prise de sang dans un échantillon d’enfants diagnostiqué avec TDAH âgé
de 8 ans. Le groupe était randomisé dans un protocole en chassé croisé et en double aveugle
avec trois doses de méthylphénidate et un placebo pour une période de quatre semaines.
Les enseignants et les parents ont répondu aux questionnaires SWAN et à une échelle
d’évaluation des effets secondaires.
Les résultats ont démontrés qu’un niveau de cortisol élevé au réveil prédit les sujets
qui ne répondent pas au traitement du TDAH, si on se fie aux rapports des parents. En plus,
la réactivité au stress élevé suggère un bénéfice additionnel d’une dose élevée de
méthylphénidate selon les enseignants. Aussi, les parents rapportent une association entre la
présence de troubles anxieux co-morbide avec le TDAH et une meilleure réponse à une
dose élevée.
Cette étude suggère qu’une forte réactivité de l’axe HHS améliore la réponse
clinique à des doses élevées, mais qu’une élévation chronique du niveau de cortisol pourrait
être un marqueur pour les non répondeurs. Les résultats de cette étude doivent être
considérés comme préliminaires et nécessitent des tests plus approfondis des interactions
possibles entre les médicaments utilisés pour traiter le TDAH et l’axe HHS.ADHD is the most common behavioural disorder in children with complex aetiology and efficacious treatments. The most prescribed medication for ADHD is methylphenidate, a psychostimulant that blocks the dopamine transporter and increases dopamine availability in the synaptic cleft. Preclinical and clinical studies show that cortisol may enhance dopamine effects. Dysregulation of the hypothalamic-pituitaryadrenal axis is also associated with many psychiatric disorders such as depression, bipolar disease, and anxiety. We hypothesized that cortisol has an influence on the efficacy of the treatment of ADHD symptoms with methylphenidate. The objective of this study was to measure the salivary level of cortisol in a sample of 8-year-old children with ADHD upon waking and in response to a venipuncture. The children were then randomized to three doses of methylphenidate and a placebo in a double-blind cross-over design. Teachers and parents rated the behaviour of the children using the SWAN and a side effect rating scale. The results showed that high morning cortisol is a good predictor of a nonresponder under active medication, as reported by parents. Also, the high stress reactivity group, but not the low stress reactivity group, demonstrated a greater benefit going to a higher dose of methylphenidate, according to teachers. In addition, parents demonstrated an association between anxiety comorbid disorders and a better response to a high dose of methylphenidate. This study suggests that a strong reactivity of the HPA axis improves the clinical response at high dose, but that chronically elevated cortisol might be a marker for non responders. The results of this study should be seen as preliminary and require further testing of the possible interactions between ADHD medication and HPA activity.
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Langel, Anne Katharina. "Basale Speichelcortisolkonzentration und Cortisol Awakening Response - Einfluss psychiatrischer Erkrankungen und schlafbezogener Faktoren bei Kindern und Jugendlichen." 2019. https://ul.qucosa.de/id/qucosa%3A37020.
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In dieser Arbeit wurde bei 137 Probanden im Alter zwischen 8 und 14 Jahren untersucht, inwiefern sich die Basalcortisolsekretion sowie die Cortisol Awakening Response bei Kindern und Jugendlichen mit internalisierenden oder externalisierenden Störungsbildern von gesunden Kindern und Jugendlichen unterscheiden. Außerdem wurde der Einfluss schlafbezogener Faktoren wie Schlafdauer, Zeitpunkt des Erwachens, Grad der Erholung und Schlafqualität auf die beiden Parameter untersucht. Diagnosegruppe, Schlafqualität und Grad der Erholung zeigten dabei keinen Einfluss auf die Cortisolparameter. Eine kurze Schlafdauer, frühes Erwachen, weibliches Geschlecht und höheres Alter der Probanden, zeigten eine signifikante Assoziation mit höheren Cortisolparametern. Die Interpretation einer HPA- Achsen- Dysregulation als diagnostischer Marker für psychiatrische Störungsbilder im Kindes- und Jugendalter sollte daher kritisch betrachtet werden. Co- Faktoren wie Geschlecht, Alter des Probanden, Schlafdauer und Zeitpunkt des Erwachens scheinen sowohl die basale Cortisolsekretion, als auch die CAR in signifikantem Maße zu beeinflussen und sollten in zukünftigen Studien zur Rolle der HPA- Achsen- Funktion im Rahmen psychiatrischer Störungsbilder sorgfältig kontrolliert werden.
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Ferreira, Eduardo Miguel Gonçalves Dias. "Stressing out decisions. The role of stress in cortico-basal ganglia loop processing and instrumental conditioning." Doctoral thesis, 2013. http://hdl.handle.net/10316/21992.
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Tese de doutoramento em Biologia, na especialidade de Fisiologia, sob orientação do Professor Doutor Carlos F. Geraldes, e do Professor Doutor Miguel Castelo-Branco, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra.Uncertainty is not only a problem in decision-making, but a prevalent quality in natural environments. Nature “equipped” us with the ability to control and coordinate behavioral and physiological adjustments imposed by the continuous reshaping of the surrounding world and of our internal needs – a process that is known as stress response. Beyond the overall complexity of moving and interacting within an uncertain world, single actions or action sequences can be triggered by their antecedents (stimulus) or performed based on their consequences (outcome). The weight of each of these associations at the time of action performance will bias if the action is executed using a habitual or a goal-directed strategy. The ability to shift between these different action strategies is necessary for adaptation to unpredictable environments. In the present series of studies, we show that a previous chronic exposure to an unpredictable environment, capable of eliciting a sustained stress response, promotes a bias toward the execution of habits versus goal-directed actions. Using two different operant tasks, we uncovered that lever pressing to obtain food rewards in rats and mice submitted to chronic unpredictable stress became insensitive to changes in outcome value and resistant to changes in action-outcome contingency. Therefore, chronic stressed animals were no longer able to adjust their actions based on their consequences, but rather actions were controlled by simple rules, and triggered by an antecedent stimulus or state. When investigating the associative and sensorimotor cortico-basal ganglia circuits known to mediate these different behavioural strategies, we found a divergent structural reorganization after chronic stress, with atrophy of medial prefrontal cortex and the associative striatum, and hypertrophy of the sensorimotor striatum. This relative structural advantage of the sensorimotor network raised the hypothesis that the competition for action control between these distinct cortico-basal ganglia circuits would already be biased when new actions had to be learned and performed after a chronic exposure to an unpredictable environment. In order to further explore this possibility, we recorded the simultaneous activity of neuronal ensembles in these frontostriatal circuits during lever press training. We reveal that habitual lever pressing in chronically stressed animals emerged concomitantly with a progressive decline in functional frontostriatal interactions, and a shift in the pattern of lever press-related activity in dorsal striatum, with the associative striatum becoming less engaged than sensorimotor striatum as training progressed. Interestingly, chronic stress effects on frontostriatal activity were not observed early in training, and did not affect baseline firing rate or the dynamic range of firing rate, suggesting that the observed shift in neuronal activity emerged during lever press training leading to a shift in action mode. The herein reported bias toward the use of habitual action strategies after exposure to an unpredictable environment could be interpreted as a preparatory response toward a context of uncertainty, where we cannot manipulate the probability of obtaining an outcome, and the use of a strategy in which actions would be controlled by simple rules, a particular stimulus or state, can be highly advantageous. However, in a world of increasing complexity where our everyday life decisions demand a permanent readjustment to major changes in the policies but also to a continuous reshaping of our current needs, the inability of stressed subjects to shift from habitual strategies to goal-directed behavior might be highly detrimental. Such impairment might be of relevance to understand the high comorbidity between stress-related disorders and addictive behavior or compulsivity, or the maintenance of old habits affecting activities spanning from our everyday life to economics.
A incerteza, mais do que um problema relacionado com a tomada de decisões, é uma característica predominante dos ambientes naturais. Em contextos de incerteza, e perante as contínuas modificações do ambiente que nos rodeia e das nossas necessidades internas, a natureza “equipou-nos” com a capacidade de adaptar as nossas ações e regular parâmetros fisiológicos – um processo conhecido como a resposta de stress. Para além de toda a complexidade inerente à interação com um mundo incerto, as ações, desde as mais simples às mais complexas, podem ser despoletadas por elementos que as antecedem (estímulos), ou executadas com base nas suas consequências (resultados). No momento em que uma ação é executada, o peso de cada uma destas associações vai definir se é utilizada uma estratégia habitual ou uma estratégia intencional. A capacidade para alternar entre a utilização de uma ou outra estratégia de ação é fundamental para a adaptação a um ambiente imprevisível. Nesta dissertação, demonstramos que a exposição prolongada a um ambiente imprevisível, capaz de gerar uma resposta de stress crónica, promove a utilização de estratégias de ação habitual, ao invés de estratégias de ação intencional. Utilizando duas tarefas instrumentais diferentes, mostramos que em ratos e murganhos sujeitos a protocolos de stress imprevisível crónico, a manipulação de uma alavanca para obter uma recompensa alimentar tornou-se insensível a modificações no valor do seu resultado, e resistente a alterações na contingência ação-resultado. Assim, os animais sujeitos a stress crónico tornaram-se incapazes de adaptar ações com base nas suas consequências; pelo contrário, as ações passaram a ser controladas por regras simples e despoletadas por um estímulo ou estado precedente. Ao estudar os circuitos associativos e sensório-motores entre o córtex e os gânglios da base (circuitos córtico-basais), que se sabia já mediarem estas diferentes estratégias comportamentais, encontramos um padrão divergente de reorganização estrutural, com atrofia do córtex pré-frontal medial e do estriado associativo, e hipertrofia do estriado sensório-motor. Esta relativa vantagem estrutural dos circuitos sensório-motores levantou a hipótese de que a competição pelo controle da ação entre os diversos circuitos córtico-basais esteja já enviesada quando a aprendizagem e execução destas ações ocorre após exposição crónica a um ambiente imprevisível. No sentido de explorar esta hipótese com maior profundidade foram executadas, no decorrer do treino de manipulação de alavancas, novas experiências com registo simultâneo da atividade de populações de neurónios nestes circuitos fronto-estriatais. Demonstramos assim que, em animais sujeitos a stress crónico, a estratégia habitual de manipulação de alavancas surge em paralelo com um declínio progressivo nas interações funcionais fronto-estriatais, e com um desvio no padrão da atividade neuronal relacionada com a manipulação da alavanca no estriado dorsal, com um menor envolvimento do estriado associativo em relação ao estriado sensório-motor à medida que o treino progride. Curiosamente, os efeitos do stress crónico na atividade fronto-estriatal não foram aparentes nas fases iniciais de treino, e não modificaram nem a taxa de disparo neuronal em repouso, nem a gama das taxas de disparo, sugerindo que as modificações observadas na atividade neuronal surgiram no decorrer do treino, levando a um desvio na estratégia de ação. A tendência aqui descrita para a utilização de estratégias de ação habitual após exposição a um ambiente imprevisível poderá ser interpretada como uma resposta de preparação para um contexto de imprevisibilidade, onde não é possível manipular a probabilidade de obter um determinado resultado; e a utilização de uma estratégia em que as ações são controladas por regras simples, tais como um estímulo ou estado particular, pode trazer grandes vantagens. No entanto, num mundo de complexidade crescente, onde decisões quotidianas são continuamente ajustadas a alterações importantes nas circunstâncias externas, assim como a permanentes modulações das nossas necessidades, a incapacidade de sujeitos previamente expostos a stress alternarem entre estratégias habituais e intencionais pode ser muito lesiva. Esta incapacidade poderá ser relevante na compreensão dos elevados níveis de comorbilidade entre perturbações relacionadas com stress e a ocorrência de dependências e comportamentos compulsivos, ou até mesmo a manutenção de hábitos antigos com impacto em atividades tão diversas como o nosso quotidiano e a economia.
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Narayanan, Ramanathan. "BAF155 regulates the genesis of basal progenitors through both Pax6-dependent and independent mechanisms during cerebral cortex development." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-002E-E3B3-8.
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Groleau, Marianne. "Identification des récepteurs cholinergiques impliqués dans le fonctionnement du cortex visuel du rongeur." Thèse, 2018. http://hdl.handle.net/1866/21815.
Full textAbstract:
Le système cholinergique est impliqué dans les phénomènes d’attention, de mémoire et d’apprentissage et les récepteurs cholinergiques régulent de multiples fonctions du système nerveux central. Néanmoins, leur rôle au niveau de la modulation des propriétés du cortex visuel reste à être établi. L’un des objectifs de cette thèse était d’étudier le rôle des récepteurs muscariniques impliqués dans le fonctionnement normal du cortex visuel. Nous avons pu déterminer que les récepteurs muscariniques sont impliqués dans l’établissement de nombreuses propriétés visuelles telles la taille des champs récepteurs, la sensibilité au contraste, la sélectivité à la fréquence spatiale et la finesse de la connectivité corticale. L’autre objectif était d’identifier les récepteurs cholinergiques impliqués dans la potentiation des capacités visuelles. Nous avons amélioré le traitement cognitif de l’information visuelle par stimulation électrique du télencéphale basal (noyau où sont localisés les corps cellulaires cholinergiques) et par la stimulation cholinergique par le donépézil, un inhibiteur de l’acétylcholinestérase. La combinaison répétée d’une stimulation visuelle et cholinergique (qu’elle soit électrique ou pharmacologique) améliore similairement l’activité corticale visuelle. Toutefois, les récepteurs impliqués ne sont pas les mêmes. Suite à la stimulation pharmacologique, ce sont principalement les récepteurs muscariniques qui influencent l’acuité visuelle de manière tardive et cette modulation est plus précoce lors de la stimulation électrique. Ces résultats démontrent que le couplage répétitif d’une stimulation cholinergique et d’une stimulation visuelle est en mesure d’améliorer l’activité corticale visuelle. Le fait de connaître les récepteurs cholinergiques impliqués permettra dans un futur proche de les cibler directement pour améliorer la fonction corticale.The cholinergic system is involved in attention, learning and memory and cholinergic receptors regulate multiple functions of the central nervous system. Nevertheless, their role in modulating the properties of the visual cortex remains to be established. One of the objectives of this thesis was to study the role of muscarinic receptors involved in the normal function of the visual cortex. We have been able to determine that the muscarinic receptors are involved in the establishment of many visual properties such as the size of the receptor fields, contrast sensitivity, spatial frequency selectivity and accuracy of the cortical connectivity. The other objective was to identify the cholinergic receptors involved in the potentiation of visual abilities. We improved the cognitive processing of visual information by electrical stimulation of the basal forebrain (the nucleus where the cholinergic cell bodies are located) and by cholinergic stimulation using donepezil, an acetylcholinesterase inhibitor. The repeated combination of visual and cholinergic stimulations (whether electrical or pharmacological) similarly enhances visual cortical activity. However, the receptors involved are not the same. Following the pharmacological stimulation, it is mainly the muscarinic receptors that influence visual acuity with a delay in the receptors expression and this modulation is earlier for the electrical stimulation. These results demonstrate that repetitive coupling of cholinergic stimulation and visual stimulation can enhance visual cortical activity. Knowing the cholinergic receptors involved will allow in a near future to target them directly to improve cortical function.