Dissertationen zum Thema „Calretinin“

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Introdução: A Displasia Neuronal Intestinal, tipo B (DNI-B) é uma doença neuromuscular gastrointestinal caracterizada por alterações complexas do sistema nervoso entérico. Seu diagnóstico depende da análise histopatológica de biópsias do reto, com mudanças dos critérios diagnósticos ao longo dos anos, o que dificulta a prática diagnóstica. O Consenso de Frankfurt, 1990, estabeleceu critérios histológicos qualitativos para diagnóstico de DNI-B, como hiperganglionose e hiperplasia do plexo nervoso submucoso. Meier-Ruge et al. 2004, 2006, definiu o diagnóstico de maneira quantitativa: mais de 20% de gânglios nervosos gigantes na submucosa, com mais de 8 neurônios cada, em 25 gânglios examinados, e em crianças maiores de 1 ano. Objetivos: Analisar as características morfológicas do sistema nervoso entérico em pacientes com DNI-B segundo os critérios do Consenso de Frankfurt de 1990, e testar a aplicabilidade dos critérios numéricos propostos por Meier-Ruge et al 2004. Pacientes e Métodos: Foram analisadas retrospectivamente peças cirúrgicas de cólon distal de 29 pacientes, com idade de 0 a 16 anos, com diagnóstico de DNI-B, em cortes histológicos processados para histologia convencional pela hematoxilina e eosina (H&E) e para imuno-histoquímica da calretinina. Resultados: Apenas 1 paciente contemplou estes critérios numéricos. Houve imunopositividade para calretinina nos neurônios, porém a contagem de neurônios foi menor em relação ao H&E (p=0,002). Não houve diferenças significativas entre os grupos etários de crianças menores e maiores de 1 ano em relação à hiperganglionose (p=0,789), número de neurônios (p=0,359), gânglios com sinais de imaturidade (p=0,664) e neurônios hipogênicos (p>0,999). Conclusões: Os critérios numéricos recomendados em cortes de 15µm, corados por painel histoquímico específico, apresentam aplicabilidade limitada quando transpostos à análise histopatológica convencional. Houve concordância pobre nos critérios analisados entre a H&E e a calretinina. Em relação à idade, nosso estudo mostrou que crianças maiores de 1 ano podem apresentar os mesmos aspectos histológicos de imaturidade neuronal que crianças menores de 1 ano, questionando a necessidade de um critério de idade para o diagnóstico da DNI-B.
Introduction: Intestinal Neuronal Dysplasia type B (INDB) is a gastrointestinal neuromuscular disease characterized by complex changes in the enteric nervous system. The diagnosis depends on the histopathological analysis of rectal biopsies and the diagnostic criteria have changed over the years, making it difficult to diagnostic practice. The Frankfurt Consensus, 1990, established qualitative criteria for the histological diagnosis of INDB, such as gigant ganglia and hyperplasia of submucosal nerves. Meier-Ruge et al. 2004, 2006, defined quantitative criteria: over 20% of giant ganglia, with more than 8 nerve cells each, on 25 ganglia examined, and in children older than one year. Objectives: Analyze the morphological characteristics of the enteric nervous system in patients with INDB according to the Frankfurt Consensus Criteria 1990 and test the applicability of the numerical criteria proposed by Meier-Ruge et al. 2004. Patients and Methods: Surgical specimens of distal colon from 29 patients, aged 0-16 years old, diagnosed with INDB, in histological sections processed for conventional histology by hematoxylin and eosin (H&E) and for immunohistochemistry of calretinin, were retrospectively analyzed. Results: Only one patient met these numerical criteria. There was immunostaining for calretinin in neurons but the neurons count was lower in relation to H&E (p=0.002). There were no significant differences between the age groups of children younger and older than 1 year old in relation to hyperganglionosis (p=0.789), number of neurons (p=0.359), ganglion with immaturity (p=0.664) and hypogenic neurons (p>0.999). Conclusions: The numerical criteria recommended for 15μm cut, stained with specific histochemical panel, have limited applicability when transferred to conventional histopathology. There was poor agreement on the criteria analyzed between H&E and calretinin. Regarding the age, our study showed that children older one year old may present the same histological features of neuronal immaturity as children younger one year old, challenging the need for an age criterion for the diagnosis of INDB.

This thesis studies sensory innervation in mammals using an organotypic co-culture of spinal cord-dorsal root ganglion and skeletal muscle of embryonic rat, the histological changes of reinnervated muscle spindles after nerve section and the localisation of the calcium-binding protein calretinin in cat mechanoreceptor organs. The immediate importance of this project concerns the better understanding of how the normal process of development differs from reinnervation following nerve lesion or section. A range of classical and well defined materials and methods as been used in the work described. The thesis Is divided into Ove chapters: Chapter 1 reviews aspects of the mechanosensory organs which have been studied experimentally in relation to their sensory innervation, including proprioceptive muscle spindle development, reinnervation, and finally, the presence of the calcium-binding protein, calretinin in the mechanoreceptor organs. This provides an introduction and background to the work. Chapter 2 describes the organotypic organisation of spinal-cord, dorsal-root ganglia and skeletal muscle co-culture in vitro. Results show that slices of the spinal-cord, dorsal- root ganglia survive well under experimental conditions and can live for several weeks with feeding every 1-3 days. Sensory neurons can develop and grow in a medium without any additional promoting factor. The presence of structurally identifiable synapses indicates that other neurons are also maintained in culture and have functional connections. In the organotypic culture new muscle fibres can form either from the original explant or from the additional explant. In chapter 3 I describe two abnormal endings present in spindles of the tenuissimus of the cat that had been reinnervated following section of the nerve more than one year previously. The reconstruction of the endings of these two spindles supports the hypothesis of modulation of the primary-ending response by the mechanical properties of the intrafusal muscle fibres, rather than by intrinsic properties of the la afferent itself. They further indicate that, in the absence of a la afferent, intrafusal-fibre differentiation can be maintained by a group II afferent. Chapter 4 concerns the localisation of the calcium-binding protein calretinin, which was studied immunohistochemically in the abductor digiti quinti medius muscle of the cat hind limb. The calretinin immunoreactivity was found in some intrafusal fibres, the primary endings and the cqjsule of the muscle spindles and the sensory terminals of tendon organs and Paciniform corpuscles. The present findings contradict a recent hypothesis that calretinin is associated with rapid adaptation, but suggest that calretinin has a specific function in muscle proprioceptors. Finally, Chapter 5 outlines the conclusions of this study and gives some suggestions for continuation of the work in the future.

Introdução: A moléstia de Hirschsprung (MH) se caracteriza pela ausência de neurônios intramurais em segmentos variáveis do intestino grosso, levando a suboclusão intestinal. Na forma mais frequente o reto-sigmoide está comprometido. A biopsia retal é o método histológico de escolha no diagnóstico da MH. O método da hematoxilina e eosina (HE) é classicamente utilizado na prática histopatológica. Nessa técnica, um fragmento de parede total do reto é processado através de parafinização, para posteriormente ser seccionado e corado por HE. Esta coloração evidencia células neurais em intestinos normais e troncos nervosos hipertrofiados nos casos de MH. É uma técnica muito simples, ainda hoje muito utilizada no diagnóstico da doença, necessitando de fragmentos grandes de reto para um maior acerto no diagnóstico. Este detalhe torna o diagnóstico do recém-nascido mais difícil. Outro método de coloração utilizado no diagnóstico da MH é o método histoquímico de pesquisa de atividade de Acetilcolinesterase (AChE). Nesta técnica é necessário apenas um pequeno fragmento de mucosa e submucosa que será congelado e depois processado. A pesquisa de AChE, nos casos de MH mostrará a presença desta enzima em quantidade aumentada, corando troncos e ou fibrilas de cor acastanhado. Este método já vem sendo utilizado pelo Instituto da Criança - HCFMUSP há mais de 30 anos e possui um acerto diagnóstico superior a 90%. Porém, por ser uma técnica mais elaborada, pouquíssimos centros no Brasil a utilizam no diagnóstico da MH. Um outro método mais recente, e que também pode ser realizado em fragmentos menores, é a marcação imunohistoquímica da calretinina, que permite a visualização dos neurônios do plexo submucoso e das fibrilas finas na região da lâmina própria em não doentes. Esta técnica também apresenta maior complexidade e, portanto, não é utilizada. A possibilidade de realizar o diagnóstico da MH através da coloração HE em fragmentos menores poderia ser uma alternativa para os serviços que não dispõe de técnicas mais especificas. Objetivos: Avaliar a concordância dos resultados obtidos pelo método de coloração HE e da calretinina com a pesquisa de atividade de AChE em fragmentos de mucosa e submucosa no diagnóstico da Moléstia de Hirschsprung. Métodos: Para este trabalho foram selecionados 50 casos arquivados em nosso laboratório. O material encontrava-se emblocado em parafina. Foram feitos 60 níveis de cada fragmento para o HE e mais 3 níveis para a calretinina. Essas lâminas foram analisadas em microscópio, fotografadas e classificadas como positivas para MH quando não foram encontradas células neurais e houve a presença de troncos nervosos, e em negativas nos casos de visualização dos neurônios. Foi realizado estudo cego por dois pesquisadores. Os resultados da leitura das lâminas foram comparados com o da AChE. Resultados: Dos 50 casos avaliados pela técnica do HE, apenas 5 discordaram do diagnóstico realizado pela AChE, com um valor de Kappa de 0,800 e acurácia 90%. Na comparação entre a calretinina e a AChE 8 casos discordaram, com um valor de Kappa de 0,676 e acurácia de 84%. Conclusões: A concordância obtida entre os métodos da AChE e HE foi satisfatória. Tornando possível a utilização do método do HE em 60 níveis de fragmento de mucosa e submucosa como alternativa para o diagnóstico da MH. A técnica imunohistoquímica da Calretinina não apresentou a concordância esperada com a pesquisa de atividade de AChE em nosso estudo
Introduction: Hirschsprung disease (HD) is characterized by the absence of intramural neurons in variable segments of the large intestine, leading to intestinal subocclusion. In the most frequent form the rectum-sigmoid is compromised. Rectal biopsy is the histological method of choice in the diagnosis of HD. The hematoxylin and eosin (HE) method is classically used in histopathological practice. In this technique, a full-thickness rectum wall fragment is processed through paraffinization, to be later sectioned and stained by HE. This staining shows neural cells in normal intestines and hypertrophied nerve trunks in cases of HD. It is a very simple technique, still used today in the diagnosis of the disease, requiring large fragments of the rectum for a better diagnosis. This detail makes the diagnosis of the newborn more difficult. The staining histochemical methods more used are the research of acetylcholinesterase activity (AChE) and staining of calretinin. However, these techniques are not available in all centers and the possibility of diagnosing HD through HE staining in smaller fragments could be valuable alternative for services that do not have more specific techniques. Objectives: To evaluate the concordance of the results obtained by the HE staining and the calretinin method with the investigation of AChE activity in fragments of mucosa and submucosa in the diagnosis of Hirschsprung\'s disease. Methods: For this study, 50 cases from our laboratory were selected. The material was embedded in paraffin. Sixty levels of each fragment were made for HE and other 3 levels for calretinin. These slides were analyzed under microscope, photographed and classified as positive for HD when no nerve cells were found and there were nerve trunks present, and in negative in cases of visualization of the neurons. A blind study was carried out by two researchers. The results of reading the slides were compared with that of AChE. Results: Of the 50 cases evaluated by the HE technique, only 5 disagreed with the diagnosis performed by AChE, with a Kappa value of 0.800 and accuracy of 90%. In the comparison between calretinin and AChE, 8 cases disagreed, with a Kappa value of 0.676 and an accuracy of 84%. Conclusions: The concordance of results from AChE and HE methods was satisfactory, allowing the possibility of the use of the HE method in fragments of mucosa and submucosa as valid alternative for the diagnosis of HD. The immunohistochemical technique of Calretinin did not show a good agreement with the AChE activity in our study

Thesis (Ph. D.)--University of Oregon, 2005.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 250 - 269). Also available for download via the World Wide Web; free to University of Oregon users.

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Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Cortical interneurons are characterized by their distinct morphological, physiological and biochemical properties, acting as modulators of the excitatory activity by pyramidal neurons, for example. Various studies have revealed differences in both distribution and density of this cell group throughout distinct cortical areas in several species. A particular class of interneuron closely related to cortical modulation is revealed by the immunohistochemistry for calcium binding proteins calbindin (CB), calretinina (CR) and parvalbumin (PV). Despite the growing amount of studies focusing on calcium binding proteins, the prefrontal cortex of primates remains relatively little explored, particularly in what concerns a better understanding of the organization of the inhibitory circuitry across its subdivisions. In the present study we characterized the morphology and distribution of neurons rich in calcium-binding proteins in the medial, orbital and dorsolateral areas of the prefrontal cortex of the marmoset (Callithrix jacchus). Using both morphometric and stereological techniques, we found that CR-reactive neurons (mainly double bouquet and bipolar cells) have a more complex dendritic arborization than CB-reactive (bitufted and basket cells) and PV-reactive neurons (chandelier cells). The neuronal densities of CR- and CB-reactive cells are higher in the supragranular layers (II/III) whilst PV-reactive neurons, conversely, are more concentrated in the infragranular layers (V/VI). CR-reactive neurons were the predominant group in the three regions evaluated, being most prevalent in dorsomedial region. Our findings point out to fundamental differences in the inhibitory circuitry of the different areas of the prefrontal cortex in marmoset
Os interneur?nios do c?rtex cerebral s?o caracterizados por suas diferentes propriedades morfol?gicas, fisiol?gicas e bioqu?micas, atuando como moduladores da atividade excitat?ria cortical dos neur?nios piramidais, por exemplo. V?rios estudos revelaram diferen?as na distribui??o e densidade deste grupo celular ao longo de diferentes ?reas corticais em diversas esp?cies. Uma classe particular de interneur?nios intimamente relacionada ? modula??o cortical ? revelada pela imunohistoqu?mica para as prote?nas ligantes de c?lcio calbindina (CB), calretinina (CR) e parvalbumina (PV). Em que pese a quantidade crescente de estudos focando nas prote?nas ligantes de c?lcio, o c?rtex pr?frontal de primatas ainda permanece relativamente pouco explorado, especialmente no que se refere a um melhor entendimento da organiza??o do circuito inibit?rio ao longo de suas subdivis?es. No presente estudo caracterizamos a morfologia e a distribui??o desse grupo neuronal nas regi?es medial, orbital e dorso-lateral do c?rtex pr?-frontal do sagui (Callithrix jacchus). Utilizando par?metros morfom?tricos e t?cnicas estereol?gicas, evidenciamos que os neur?nios reativos a CR (especialmente c?lulas em duplo-buqu? e bipolares) possuem arboriza??o dendr?tica mais complexa quando comparados aos neur?nios reativos a CB (neur?nios de tufos duplos e c?lulas em cesto) e PV (c?lulas em candelabro). A densidade dos neur?nios reativos a CB e CR ? mais elevada nas camadas supragranulares (II/III), enquanto os neur?nios reativos a PV se concentram predominantemente nas camadas infragranulares (V/VI). Os neur?nios reativos a CR foram o grupo predominante nas tr?s regi?es avaliadas, sendo mais prevalente na regi?o dorsolateral. Nossos achados apontam para diferen?as cruciais no circuito inibit?rio ao longo das diferentes ?reas do c?rtex pr?-frontal do sagui

Hirschsprung’s disease is a common pathology in pediatric surgery. Besides, long-term outcome of surgically-treated patients remains a crucial issue. The management of Hirschsprung’s disease has remarkably advanced over the years, but difficulties persist particularly in the developing countries (such as Vietnam), where essential diagnostic procedures, such as preoperative histopathological exploration techniques/ facilities (mainly for acetylcholinesterase staining), or adequate postoperative management and follow-up requirements are unavailable.We, therefore, contemplated to work-out a relevant histo-diagnostic approach to overcome these constraints that limit our diagnostic approaches, namely, in Vietnam, and we introduced a “less-demanding” diagnostic approach, namely calretinin immunohistochemical staining which is known to be adequate for formalin-fixed tissues (and thus not necessitating frozen section equipment). We thus used calretinin immunohistochemistry in a prospective study on a large cohort of Vietnamese HD cases. Results showed that rectal suction biopsy using calretinin immunohistochemistry provides an effective histopathological diagnostic tool that can replace AChE and provides a valuable evaluating approach for both preoperative and postoperative management.In addition, we also studied long-term outcome in operated patients and impact of postoperative morbidities on their quality of life. Indeed, a long-term multidisciplinary management with dedicated procedures such as anorectal manometry is essentially required for patients with severe defecation disorders.
Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished

Neurodegenerative diseases are associated with extensive physical and mental debilitation, significant costs to the healthcare system, as well as great emotional and financial burden to the patients, their families and care providers. Despite progress in our understanding of the mechanisms behind neurodegenerative diseases, the vast majority are still currently untreatable. Synapses are important pathological targets in a range of disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and lysosomal storage disorders, such as Batten disease. Loss of synaptic connections and impairments in synaptic function are present in the initial stages of neurodegenerative conditions and throughout the course of disease progression. Therefore, synaptoprotective strategies are regarded as a potentially key factor in the development of effective therapies aimed at preventing or halting neurodegeneration. Despite the continuously growing body of research elucidating the molecular mechanisms that modulate synaptic function and vulnerability, the contribution of these pathways to neurodegenerative diseases is far from fully characterized. In addition, there are frequent issues regarding the applicability of the research performed using in vitro and small animal models of disease to develop therapeutic strategies for use in human patients. In the work described in this thesis, we initially validated the involvement of a selection of key synaptic targets, previously identified as regulators of synaptic degeneration in lower animal models, including mice and Drosophila, in a large animal model of neurodegenerative disease: CLN5 Batten sheep. Subsequently, we explored two of these individual synaptic protein targets in more detail (calretinin and α-synuclein), to further investigate their contribution to synaptic function and stability. Calretinin is a poorly characterized protein, primarily known for its calcium buffering capacities and high levels of expression in a subpopulation of interneurons. In this work, we show calretinin is expressed in previously unreported cell populations, including motor axons and synapses from the peripheral nervous system, and that it is enriched in synapses in vitro. Furthermore, we show calretinin responds dynamically to synaptic activity and is directly involved in neurodegenerative pathways, as demonstrated by its ability to influence the course of Wallerian degeneration and apoptotic cell death. α-synuclein plays a central role in the pathophysiology of Parkinson’s disease and contributes to the maintenance of synaptic transmission and mitochondrial function. However, questions still remain about how to effectively manipulate α- synuclein to obtain therapeutic benefits. Therefore, we sought to explore downstream targets of α-synuclein in order to uncover new pathways through which this protein may influence synaptic stability. Using proteomics on mice lacking α-synuclein and in vitro cell systems we identified sideroflexin 3 (sfxn3). We show sfxn3 is localized at the inner mitochondrial membrane and that it functions outside the main canonical pathways of mitochondria energy production. In addition, overexpression of sfxn3 in Drosophila led to a significant loss of synaptic boutons at the level of the neuromuscular junction, suggesting regulated levels of sfxn3 are important for the maintenance of synaptic connections. Altogether, the work developed in this thesis provides novel insights into pathways regulating synaptic stability and function. We not only provide evidence that the molecular targets studied are affected in a large animal model of neurodegenerative disease, and are therefore likely to be relevant to studies in human conditions, but we also uncover two new molecular targets capable of independently regulating synaptic form and function.

Tauopathy, which results from the oligomerization of misfolded tau protein in neurons, is a feature present in a number of neurodegenerative diseases and a hallmark of Alzheimer’s Disease (AD). Tau is an important phosphoprotein that regulates the assembly of microtubules, but tauopathy can occur when tau becomes hyperphosphorylated. Phosphorylation prevents tau from binding to tubulin, which results in cytosolic accumulation of tau and eventual oligomerization. This abnormal accumulation of tau leads to the spreading of hyperphosphorylated tau to downstream synaptically connected neurons through an unknown mechanism. In AD, the hippocampus is one of the first brain structures to be affected by tauopathy in humans. According to previous research, tauopathy occurs primarily between principal cells in the hippocampus. The involvement of local inhibitory interneurons in tauopathy and their potential role in AD is more controversial. Previous research suggests that tau pathogenesis primarily affects principal cells; however, given the importance, diversity, and function of interneurons in the hippocampus, it is important to gain a better understanding of the interneuron subtypes that may be impacted by the spread of trans-synaptic tau into the hippocampus. Understanding the involvement of interneurons in trans-synaptic tau transmission is important to understanding neurodegeneration in AD and other neurodegenerative disorders. To investigate this, both male and female genetically-modified mice underwent surgery to examine the trans-synaptic spread of pathogenic tau (EGFP-Tau P301L) from the entorhinal cortex to hippocampal neurons. Histology and imaging analysis of brain sections were performed to examine the hippocampal cells impacted by trans-synaptic spread of tau. Results show that pathogenic tau can trans-synaptically spread from presynaptic neurons in the entorhinal cortex into downstream hippocampal interneurons and also that hippocampal interneurons are capable of trans-synaptically spreading tau. Future studies examining the specific subtypes of hippocampal interneurons vulnerable to trans-synaptic spread of tau will be important for a better understanding of disease progression, which could lead to uncovering new therapeutic targets for neurodegenerative diseases, like AD, which are associated with tauopathy.

Les cellules souches neurales (CSNs) de la zone sous-ventriculaire (ZSV) présentent une activité germinale intense tout au long de la vie d'un individu. Les CSNs postnatales sont régionalisées en microdomaines exprimant des facteurs de transcription spécifiques et générant des sous-types neuronaux distincts dans le bulbe olfactif (BO). Les interneurones calrétinine (CalR+) représentent la plus grande population d'interneurones périglomérulaires (PG) du BO produits après la naissance. Cependant, contrairement à d'autres, il existe peu d'informations concernant leur origine, leur diversité et leur fonction dans le BO, ainsi que les facteurs de transcription impliqués dans leur génération. Des études antérieures ont mis en évidence que les interneurones CalR + PG sont générés à la fois par les microdomaines médial et dorsal de la ZSV, et ont suggéré que le facteur de transcription Sp8 serait impliqué dans leur génération. Ce travail de thèse a eu pour objectif : 1) d'affiner les approches actuelles afin de manipuler l'expression génique dans les CSNs de la ZSV postnatale d'une manière contrôlée temporellement, 2) d'explorer l'origine et la fonction des interneurones CalR + périglomérulaires, 3) d'étudier le rôle du facteur de transcription Sp8 dans le codage transcriptionnel de la spécification des interneurones CalR + périglomérulaires ainsi que leur maturation. Ainsi, une approche d'électroporation postnatale classique a été affinée afin de pouvoir manipuler l'expression des gènes dans les CSNs de la ZSV et ainsi permettre de cartographier le devenir à long terme de la progénie des CSNs et de manipuler génétiquement ces CSNs à une étape précise de leur différentiation. Le perfectionnement de cette approche a permis d'identifier deux sous-populations d'interneurones CalR + présentant des origines spatiales et temporelles différentes après la naissance, ainsi que d'explorer les implications fonctionnelles et morphologiques de cette diversité. Ainsi, une fraction importante et non décrite d'interneurones CalR + PG présente des propriétés de neurones immatures (c'est-à-dire qu'elle reçoit peu d'entrées synaptiques et est faiblement excitable), remettant en question leur rôle dans le traitement de l'information olfactive. Enfin, des manipulations génétiques du facteur de transcription Sp8 à divers stades de la différenciation des interneurones CalR+ ont mis en évidence son rôle dans la survie à long terme des interneurones CalR + PG matures, tout en excluant un rôle dans leur spécification précoce. Ces résultats amène ainsi un éclairage nouveau sur l'origine, la diversité et le codage transcriptionnel des interneurones CalR + PG et appellent à une caractérisation plus précise de leur rôle dans le traitement de l'information olfactive
The subventricular zone (SVZ) is a brain region that shows intense germinal activity throughout postnatal life. The postnatal SVZ is subdivided in microdomains containing neural stem cells (NSCs) that express defined transcription factors and generate distinct neuronal subtypes in the olfactory bulb (OB). Calretinin-expressing (CalR+) interneurons represent the largest population of OB periglomerular interneurons produced after birth. Yet, in contrast to others, limited information exists regarding their origin, diversity and function in the OB, as well as the transcription factors that guide their generation. Previous studies highlighted that CalR+ PG interneurons are generated by both the medial and dorsal SVZ microdomains, and suggested that the transcription factor Sp8 is involved in their generation.This work aimed at 1) refining current approaches for manipulating gene expression in postnatal SVZ NSCs in a temporally controlled manner, 2) exploring the origin and the function of CalR+ periglomerular neurons, 3) investigating the role of Sp8 in the transcriptional coding of CalR+ periglomerular interneurons specification and maturation.Refinement of the classical electroporation approach allowed the long-term fate mapping and timely-controlled genetic manipulation of NSCs of the SVZ. Using this refined approach allowed identifying two subpopulations of CalR+ interneurons that show different spatial and temporal origins after birth, as well as to explore the functional and morphological correlates of this diversity. A large and previously non-described fraction of CalR+ periglomerular interneurons exhibits properties of immature neurons (i.e. little synaptic inputs and weak excitability), questioning their role in olfactory processing. Finally, genetic manipulations of the transcription factor Sp8 at different stages during CalR+ interneuron differentiation highlighted its role in the long-term survival of mature CalR+ periglomerular interneurons, while excluding a role in their early specification. Altogether these results shed new lights on the origin, diversity and transcriptional coding of CalR+ periglomerular i nterneurons and call for a characterization of their role in olfactory processing

Les épilepsies du lobe temporal médian sont parmi les formes les plus courantes d'épilepsie partielle pharmaco-résistante de l'adulte.Ces épilepsies sont caractérisées par la survenue de crises récurrentes spontanées associées à des décharges synchrones de populations neuronales générées par un réseau multi structural Zone Epileptogène. Le noyau supramammillaire (SuM) innervant tous les cortex limbiques. Chez le rat, il a été démontré qu’il était impliqué dans le contrôle des rythmes thêta de l’hippocampe et des fonctions associées telles que le sommeil paradoxal, ainsi que l’apprentissage et la mémoire émotionnelle. Il a été démontré que les projections des neurones de la région latérale du SuM (SuML) qui innervent le gyrus dentelé dorsal (dDG) présentent un phénotype unique à la foie GABAergique et Glutamatergique. De plus cette voie est réorganisée chez les animaux épileptiques. Dans cette thèse, nous démontrons que:Tous les neurones du SuML innervant le DG co-expriment les marqueurs pour les neurotransmissions GABAergique et glutamatergique. L'activation de cette voie augmente la puissance et la fréquence des oscillations thêta ainsi que la puissance du gamma,pendant le SP et induit la décharge des CGs.La population de neurones GABA / GLU du SuML innervant le dDG est hétérogène. Parmi ces neurones,70% contiennent la calrétinine et 30% n'en contiennent pas.Chez les souris épileptiques, la voie SuML-dDG est réorganisée . Nos résultats préliminaires utilisant les techniques d’optogénétique in vivo montrent que l'activation ou l'inactivation de cette voie ne modifie pas la durée de la crise. Cependant, cette voie module la variabilité de la contenu fréquentiel des crises
Mesial temporal lobe epilepsies are among the most common clinical forms of drug-resistant partial epilepsies in adults. These epilepsies are characterized by the occurrence of spontaneous recurrent seizures associated with excessive and hypersynchronous discharges of neuronal populations generated by a multi-structural epileptogenic zone involving several regions of the limbic system. The Supramammillary nucleus (SuM) is innervating all limbic cortex. In rat, it has been shown to be involved in the control of hippocampal theta rhythms and associated functions such as REM sleep as well as emotional learning and memory. More recently, it was shown that the projections from neurons of lateral region of the SuM (SuML) that innervate the dorsal dentate gyrus (DG) display a unique GABAergic and Glutamatergic neurotransmitter phenotype and this pathway is reorganized in epileptic animals. In this thesis,we demonstrated that: All the neurons from the SuML innervating the dDG co-express markers for both GABAergic and glutamatergic neurotransmissions. Activation of this pathway increases theta power and frequency as well as gamma power during REM sleep and induced net firing of some GCs. The population of GABA/GLU SuML neurons innervating the dDG is heterogeneous. Among these neurons 70% contain calretinin whereas 30% do not. In epileptic mice the SuML-dDG pathway is reorganized . Our preliminary results using in vivo optogenetic show that activation or inactivation of this pathway do not modify the seizure duration. However, this pathway modulates the variability of the seizure frequency content

Lo studio della sfera emozionale è stato da sempre oggetto d’interesse da parte di molti ambiti della Scienza, nonostante la sua perfetta mappatura costituisca ancora oggi un’ambizione non del tutto raggiunta. Comprendere quale sia il meccanismo specifico di genesi ed elaborazione delle emozioni e quali aree encefaliche ne siano responsabili, costituisce per gli scienziati una sfida di grande interesse. L’importanza dell’Amigdala nello studio e nella comprensione delle emozioni è conseguente alla scoperta di come questa struttura sia responsabile della genesi di un'emozione: la paura. Antica e ben radicata nel percorso evolutivo di ogni specie, la reazione di paura davanti ad un pericolo ha una funzione positiva: protegge da stimoli potenzialmente dannosi e, di base, non si apprende: tutti sono in grado di provare paura. L’Amigdala, denominata anche complesso nucleare amigdaloideo, è una struttura eterogenea, costituita da circa 13 nuclei e localizzata nella parte mediale del lobo temporale. I nuclei amigdaloidei vengono divisi in 3 gruppi: nuclei profondi, nuclei superficiali ed altre aree amigdaloidee. Le caratteristiche citoarchitettoniche e neurochimiche del complesso nucleare amigdaloideo sono state largamente studiate nei Mammiferi terrestri quali: ratto, scimmia, gatto ed Uomo. In letteratura non sono presenti particolari riferimenti ai Mammiferi marini. Per questo motivo la presente ricerca si propone di mostrare le caratteristiche citoarchitettoniche e neurochimiche del nucleo centrale dell’amigdala di tursiope (Tursiops truncatus), con particolare riferimento alle caratteristiche morfometriche dei neuroni esprimenti parvalbumina, calbindina-D28k e calretinina.

Foi descrita a presença do receptor P2X2 no sistema nervoso entérico e foi constatado que a desnutrição afeta os neurônios mioentéricos. Este projeto analisou os neurônios dos plexos mioentérico (PM) e submucoso (PS) imunorreativos ao receptor P2X2(ir), calbindina (Calb-ir), calretinina (Calr-ir), colina acetil transferase (ChAT-ir) e ao óxido nítrico sintase (NOS-ir) do íleo de ratos submetidos à desnutrição protéica pré e pós-natal e a renutrição pós-natal. Foram utilizados íleos de animais nutridos (N42), desnutridos (D42) e renutridos (RN42). Os resultados do PM e PS demonstraram 100% de neurônios Calb-ir, Calr-ir, ChAt-ir e NOS-ir expressavam o receptor P2X2-ir nos grupos. As densidades neuronais do PM e PS demonstraram aumento de 30% e 25% respectivamente, dos neurônios receptor P2X2-ir, Calr-ir, ChAT-ir e NOS-ir no grupo D42 e, recuperação no grupo RN42, os neurônios Calb-ir aumentaram 60% no PS. O perfil neuronal do PM mostrou diminuição de 26% nos neurônios receptor P2X2-ir e Calr-ir no grupo D42 e, no PS houve diminuição nos neurônios receptor P2X2-ir. Concluiu que a desnutrição afetou os neurônios entéricos e houve recuperação na renutrição, isto pode influenciar as funções do trato gastrintestinal.
It is showed the expression of the P2X2 receptor in the enteric nervous system; it was observed that undernutrition affect the myenteric neurons. This project analyzed the ileum myenteric (MN) and submucous (SN) neurons immunoreactive to P2X2 receptor, calbindin (Calb-ir), calretinin (Calr-ir), coline acetil transferase (ChAT) and nitric oxide sintase (NOS) of the animals submitted to pre- and postnatal protein deprivation and postnatal refeeding. Ileum was used from nourished (N42), undernourished (D42) and Refeeding (RN42) animals. The results showed 100% coexpression myenteric and submucous Calb-ir, Calr-ir, ChAt-ir e NOS-ir neurons with P2X2-ir receptor. The myenteric and submucos neuronal density showed increase of the 30% and 25% respectively, of the P2X2-ir, Calr-ir, ChAT-ir e NOS-ir neurons of the D42 group, the Calb-ir neurons increase 60% in the SN. It was observed in the MN neuronal profile decrease of the 26% of the P2X2-ir and Calr-ir in the RN42 group and recover in the RN42, there was decrease of the P2X2-ir receptor neurons in the submucous plexus. The conclusion demonstrated that undernutrition affects the enteric neurons and there was recuperation in the refeeding, this can influence the gastrointestinal functions.

Este projeto, analisou a distribuição dos neurônios nos plexos mioentérico (PM) e submucoso (PS) imunorreativos aos receptores P2X2 (ir) e P2X7 (ir), calbindina (Calb-ir), calretinina (Calr-ir), colina acetil transferase (ChAT-ir) e ao óxido nítrico sintase (NOS-ir) do colo distal de ratos submetidos à desnutrição a renutrição protéica. Utilizaram-se colos distais de ratos nutridos (N42), desnutridos (D42) e renutridos (RN42). Os resultados do plexo PM, demonstraram que 100% dos neurônios Calb-ir, Calr-ir, ChAT-ir e NOS-ir, expressavam os receptores P2X2-ir e P2X7-ir nos três grupos. A densidade neuronal no PM, demonstrou um aumento de 20% a 97% dos neurônios receptores P2X2-7-ir, Calr-ir, ChAT-ir e NOS-ir e no PS foi de 29% a 75%, ambos D42 e recuperação no RN42. O perfil neuronal P2X7-ir, Calb-ir, Calr-ir e ChAT-ir do PM demonstrou diminuição de 28% a 40% e no PS os neurônios P2X2-7-ir, Calb-ir e ChAT-ir de 19% a 47% no D42. Concluí-se que, a desnutrição afeta os neurônios entéricos havendo recuperação na renutrição, podendo influenciar nas funções gastrintestinais.
The aim of the work was to analyze the distal colon myenteric (MN) and submucous (SN) neurons immunoreactive for P2X2-7 receptors, calbindin (Calb-ir), calretinin (Calr-ir), choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) of the animals submitted to undernutrition and refeeding proteic. Distal colon was used from nourished (N42), undernourished (D42) and refeeding (RN42) rats. The results have shown 100% coexpression of the myenteric and submucous Calb-ir, Calr-ir, ChAt-ir e NOS-ir neurons with P2X2-7-ir receptors. The MN density have shown increase of the 20% and 97% of the P2X2-7-ir, Calr-ir, ChAT-ir e NOS-ir neurons of the D42 group, and the SN have been increased 29% a 75% in the D42 group. In the MN neuronal profile have shown decrease P2X7-ir, Calb-ir, Calr-ir and ChAT-ir neurons of the 28% to 40% and in the PS P2X2-7-ir, Calb-ir and ChAT-ir of the 19% a 47% neurons in the D42 group. I concluded that, the undernutrition affects the enteric neurons and there was recuperation in the refeeding, this can influence the gastrintestinal functions.

Research Doctorate - Doctor of Philosophy (PhD)
The spinal cord dorsal horn (DH) represents an important area in the processing of sensory information. As the first point in the central nervous system (CNS) where peripheral signals input, our understanding of information processing that occurs here is crucial if we are to better manage sensory dysfunction. Chapter 1 details this background along with emphasising the significant heterogeneity that exists in this region, which has made the elucidation of specific DH circuit’s difficult. Fortunately, advances in molecular and genetic techniques have facilitated the targeting of individual neuron populations. Building from this technology, experiments in this thesis examine the role of a specific population of DH neurons that can be identified by expression of the calcium binding protein calretinin (CR). CR has previously been shown to be expressed on a sub population of excitatory interneurons, however little work has been done to identify their role in spinal pain processing. Chapter 2 first examines the electrophysiological and morphological properties of CR+ neurons in the DH. In this analysis I identified two functionally and morphologically distinct populations of CR+ neurons, referred to as Typical and Atypical. Typical CR neurons exhibited features consistent with excitatory interneurons, including high frequency spontaneous excitatory input, delayed action potential (AP) discharge patterns, A-type potassium currents and central, radial or vertical cell morphologies. While, Atypical CR neurons showed inhibitory interneuron characteristics, including low frequency spontaneous excitatory input, tonic AP discharge patterns, Ih currents and islet-like morphology. The spontaneous inhibitory input received by these two populations of CR+ neurons also differed. Typical, excitatory CR neurons receive mixed inhibition from both GABAergic and glycinergic sources, whereas, inhibition of the inhibitory CR+ neurons was glycine dominant (Chapter 3). In order to look at the functional connections of CR+ neurons within the DH I used channel rhodopsin assisted circuit mapping. These experiments identified a high level of connectivity both amongst CR+ neurons and to other, unidentified populations. Importantly, among the identified connections CR+ neurons provided input to identified projection neurons, the functional output cells of the dorsal (sensory) spinal cord. To further resolve the postsynaptic targets of CR+ neurons I next applied spinal optogenetic stimulation in anaesthetised mice, before undertaking c-Fos immunohistochemistry to label activated populations and identify them with neurochemical markers of known DH subpopulations. This showed that, in addition to projection neurons (identified here by NK-1R labelling), CR+ neurons activated a substantial inhibitory population, and selective populations of excitatory interneurons. Finally, I developed a surgical approach to chronically implant a fibre optic probe over the spinal cord. This allowed me to assess the behavioural phenotype associated with spinal CR+ neuron activation. These results showed that in awake and behaving animals CR+ neuron activation generates a strong nocifensive behavioural response that outlasts optogenetic stimulation, shifts over the body surface, potentiates when stimulation is repeated, is blocked by morphine administration, and produces a conditioned place aversion. Overall, my thesis provides a thorough characterisation of CR+ DH neurons at a single cell, circuit and behavioural level. This has greatly contributed to our understanding of sensory processing in the spinal cord, particularly excitatory interneurons, an important population, which has not previously been studied in this level of detail.

Calretinin (CR) and parvalbumin (PV) neurons are inhibitory interneurons (INs) that play important roles in the modulation of excitatory pyramidal neurons. They are found in many species are and throughout the neocortex. However, their characteristics vary between species and brain region. The aim of this study was to compare the density, distribution, and inhibitory signaling of CR and PV neurons in monkey primary visual cortex (V1), monkey lateral prefrontal cortex (LPFC), mouse V1 and mouse frontal cortex (FC). Coronal brain slices from each of the species and brain regions were stained using immunohistochemistry and then the slices were scanned using high-resolution confocal imaging. High resolution image stacks were used to count the somata of CR and PV. The vesicular gamma aminobutyric acid (GABA) transporter (VGAT), CR and PV particles were analyzed to quantify these inhibitory markers in monkey V1, LPFC, and mouse V1 and FC. There were significant differences in the laminar distribution of CR and PV neurons in that CR neurons were concentrated in L2/3 and PV neurons were concentrated in L2-5. In L2/3, Monkey V1 had more CR neurons than did monkey LPFC. Furthermore, there were a greater number of PV neurons in monkey and mouse V1 compared to monkey LPFC and mouse FC. In L2/3, monkey V1 had the highest number of PV neurons. In L5, there significantly greater PV neurons in mouse V1 compared to monkey V1. There was significantly higher density of CR neurons in the upper middle layers of Monkey V1 compared to mouse V1 and monkey LPFC compared to mouse FC. The upper middle layers of monkey V1 had significantly higher density of PV neurons compared to monkey LPFC and mouse V1. There was significantly higher density of VGAT particles in monkey V1 and LPFC compared to mouse V1 and FC, which indicates more inhibitory synapses. There were significantly more VGAT+ boutons colocalized with PV+ boutons than CR+ boutons. Finally, discriminant analysis and hierarchical cluster analysis show that species is the largest separating factor between monkey V1, LPFC and mouse V1 and FC. Mouse V1 and FC are very similar, and monkey V1 and LPFC are dissimilar from one another. This data, united with comparative data on pyramidal neurons, demonstrates that neurons have differences between species, and monkeys have more regional specialization than mice.

In the mammalian neocortex, GABAergic interneurons play a variety of roles in higher-order brain functions as key components of brain circuits. Many studies have revealed properties of pyramidal neurons, but the functions of interneurons are relatively poorly understood. Focusing on inter-species differences, previous work in our lab (Gilman et al, 2017) revealed pyramidal neuron differences in monkey and mouse primary visual (V1) and frontal (FC) cortices. Here, we designed a comparative study in a similar context to reveal knowledge of Calretinin (CR)-expressing interneurons in monkey and mouse V1 and area FA of the mouse, prefrontal cortical area 46, and V1 of the monkey. Monkey and mouse brain tissues were immuno-stained, scanned with a confocal microscope and 3D reconstructed using NeuroLucida 360. Semi-automated analyses revealed that mouse CR interneurons on both brain regions were larger and showed more dendritic branching. Cell type sorting following the previous classification method by Cauli et al (2014) showed distinctive cell type distribution Monkey V1. CR interneurons in V1 regions in both species showed features that differentiate them from FC interneurons, including more node counts than those in FC. Also, a sudden increase in average V1 dendritic diameter after its 75% length progression was shown between species. These findings have provided gap-filling knowledge about CR+ interneuron species-specific differences in V1 and PFC, which gives a foundation for inter-species data comparison.

Similarities between the acanthomatous epulis and ameloblastomas resulted in debate regarding the nature and origin of the acanthomatous epulis found in dogs. In an attempt to elucidate the origin and character of the acanthomatous epulides, this study aimed to find suitable cell markers to identify odontogenic epithelium versus oral epithelium in developing dog teeth in order to use in future research on the pathogenesis and pathology of odontogenic neoplasms in dogs. As specific markers for odontogenic epithelium have not been described in dog tissue, proposed markers of odontogenic epithelium of human and rat tissues were tested on developing dog teeth. Keratin 14, keratin 19, amelogenin, p75 neurotrophin receptor and calretinin have been proposed as markers for inner enamel epithelium and/or ameloblasts in human and rat tissue and was therefore included in this study. Keratin 14 and keratin 19 can not be regarded as specific markers of odontogenic epithelium as various other types of epithelium also stained positive with these markers. Amelogenin could be a promising marker to distinguish between odontogenic tumours and non-odontogenic tumours as it was only detected in odontogenic tissues in this study. However, amelogenin has also been observed in other tissues in dogs and rats, and therefore further studies on this protein will be needed to elucidate the expression profile of amelogenin in odontogenic versus non-odontogenic tissues in dogs. p75 Neurotrophin receptor expression was restricted to certain regions of the inner enamel epithelium and no staining was observed in other epithelial cells. It therefore seems to be a promising marker to differentiate between odontogenic and non-odontogenic epithelium, but the widespread staining observed in the mesenchymal tissue makes differentiation between odontogenic and non-odontogenic stromal elements impossible. Calretinin staining was observed in the alveolar epithelial cells directly overlying the developing tooth germ, proposed as the oral epithelium where the dental lamina takes origin from, as well as the dental laminae and Serres rests. No staining was observed in the rest of the oral epithelium and it can therefore be proposed that calretinin could be a useful marker to distinguish between odontogenic and non-odontogenic epithelial cells. In light of the results found in this study on foetal tissue, the expression profile may be different in adult tissue. Odontogenic tumours in adult dogs may originate from remnants of odontogenic tissue like Serres rests and Malassez rests. It is therefore proposed that this study be repeated on adult dog tissue with specific reference to Serres rests, Malassez rests and the associated gingiva Copyright
Dissertation (MSc)--University of Pretoria, 2009.
Oral Pathology and Oral Biology
unrestricted

La période postnatale et l’expérience sensorielle sont critiques pour le développement du système visuel. Les interneurones inhibiteurs exprimant l’acide γ-aminobutyrique (GABA) jouent un rôle important dans le contrôle de l’activité neuronale, le raffinement et le traitement de l’information sensorielle qui parvient au cortex cérébral. Durant le développement, lorsque le cortex cérébral est très susceptible aux influences extrinsèques, le GABA agit dans la formation des périodes critiques de sensibilité ainsi que dans la plasticité dépendante de l’expérience. Ainsi, ce système inhibiteur servirait à ajuster le fonctionnement des aires sensorielles primaires selon les conditions spécifiques d’activité en provenance du milieu, des afférences corticales (thalamiques et autres) et de l’expérience sensorielle. Certaines études montrent que des différences dans la densité et la distribution de ces neurones inhibiteurs corticaux reflètent les caractéristiques fonctionnelles distinctes entre les différentes aires corticales. La Parvalbumine (PV), la Calretinine (CR) et la Calbindine (CB) sont des protéines chélatrices du calcium (calcium binding proteins ou CaBPs) localisées dans différentes sous-populations d’interneurones GABAergiques corticaux. Ces protéines tamponnent le calcium intracellulaire de sorte qu’elles peuvent moduler différemment plusieurs fonctions neuronales, notamment l’aspect temporel des potentiels d’action, la transmission synaptique et la potentialisation à long terme. Plusieurs études récentes montrent que les interneurones immunoréactifs (ir) aux CaBPs sont également très sensibles à l’expérience et à l’activité sensorielle durant le développement et chez l’adulte. Ainsi, ces neurones pourraient avoir un rôle crucial à jouer dans le phénomène de compensation ou de plasticité intermodale entre les cortex sensoriels primaires. Chez le hamster (Mesocricetus auratus), l’énucléation à la naissance fait en sorte que le cortex visuel primaire peut être recruté par les autres modalités sensorielles, telles que le toucher et l’audition. Suite à cette privation oculaire, il y a établissement de projections ectopiques permanentes entre les collicules inférieurs (CI) et le corps genouillé latéral (CGL). Ceci a pour effet d’acheminer l’information auditive vers le cortex visuel primaire (V1) durant le développement postnatal. À l’aide de ce modèle, l’objectif général de ce projet de thèse est d’étudier l’influence et le rôle de l’activité sensorielle sur la distribution et l’organisation des interneurones corticaux immunoréactifs aux CaBPs dans les aires sensorielles visuelle et auditive primaires du hamster adulte. Les changements dans l’expression des CaBPs ont été déterminés d’une manière quantitative en évaluant les profils de distribution laminaire de ces neurones révélés par immunohistochimie. Dans une première expérience, nous avons étudié la distribution laminaire des CaBPs dans les aires visuelle (V1) et auditive (A1) primaires chez le hamster normal adulte. Les neurones immunoréactifs à la PV et la CB, mais non à la CR, sont distribués différemment dans ces deux cortex primaires dédiés à une modalité sensorielle différente. Dans une deuxième étude, une comparaison a été effectuée entre des animaux contrôles et des hamsters énucléés à la naissance. Cette étude montre que le cortex visuel primaire de ces animaux adopte une chimioarchitecture en PV similaire à celle du cortex auditif. Nos recherches montrent donc qu’une suppression de l’activité visuelle à la naissance peut influencer l’expression des CaBPs dans l’aire V1 du hamster adulte. Ceci suggère également que le type d’activité des afférences en provenance d’autres modalités sensorielles peut moduler, en partie, une circuiterie corticale en CaBPs qui lui est propre dans le cortex hôte ou recruté. Ainsi, nos travaux appuient l’hypothèse selon laquelle il serait possible que certaines de ces sous-populations d’interneurones GABAergiques jouent un rôle crucial dans le phénomène de la plasticité intermodale.
The postnatal period and sensory experience are critical for the development of the visual system. The inhibitory interneurons expressing the γ-aminobutyric acid (GABA) play an important role in the control of neural activity, refinement and treatment of sensory information which reaches the cerebral cortex. During development, when the cerebral cortex is very likely to be influenced by extrinsic factors, GABA acts in the formation of critical period of receptivity as well as in experience dependent plasticity. Thus, this inhibitory system adjusts the functioning of the primary sensory areas according to the specific conditions of activity from the environment, cortical afferents (e.g. of thalamic origin), and sensory experience. Several studies show that differences in the distribution and density of these inhibitory interneurons tend to reflect functional discrepancies between the different neocortical areas. Parvalbumin (PV), Calretinin (CR) and Calbindin (CB) are calcium-binding proteins (CaBPs) found in different sub-populations of GABAergic cortical interneurons. These proteins buffer intracellular calcium levels, which can in turn modulate several neural functions, notably the temporal aspect of action potentials, synaptic transmission and long-term potentiation. Several recent studies are showing that CaBPs immunoreactive (ir) interneurons are also very sensitive to experience and sensory activity during development and adulthood. Therefore, these neurons may have a critical role in intermodal plasticity or compensatory processes between primary sensory cortices. In the hamster (Mesocricetus auratus), after enucleation at birth, the primary visual cortex can be recruited by other sensory modalities such as touch and audition. After this type of visual deprivation, there is establishment of permanent ectopic projections between the inferior colliculus (IC) and the lateral geniculate nucleus (LGN). This phenomenon leads to the rerouting of auditory information to the primary visual cortex (V1) during postnatal development. By using this animal model, the general objective of this thesis is to study the influence and the role of sensory activity on the distribution and organization of cortical interneurons that display immunoreactivity for CaBPs in the primary visual and auditory sensory areas in adult hamsters. Changes in the expression of CaBPs were quantitatively determined by assessing the laminar distribution profiles of cell bodies revealed by immunohistochemistry. In the first experiment, we studied laminar distribution of CaBPs in the primary visual (V1) and auditory (A1) cortices of normal hamsters. PVir and CBir, but not CRir neurons, are distributed in a dissimilar fashion between the two primary cortices devoted to each sensory modality. In the second study, a comparison was performed between control animals and hamsters which were enucleated at birth. The results of this study show that the primary visual cortex of these animals adopts a PVir chemoarchitecture similar to that of the auditory cortex. Our research shows that the abolition of visual activity at birth can influence the expression of CaBPs in V1 of the adult hamster. The present results also suggest that the type of activity in afferents from other sensory modalities can at least in part modulate the cortical circuitry of CaBPs in the host or recruited cortex. Thus, our work supports the hypothesis that sub-populations of GABAergic interneurons may play a critical role in the intermodal cortical plasticity.