Dissertations / Theses on the topic 'Presynaptic inhibition'

Thesis (Ph.D.)--Indiana University, Dept. of Kinesiology, 2007.<br>Source: Dissertation Abstracts International, Volume: 68-07, Section: B, page: 4882. Adviser: John S. Raglin. Title from dissertation home page (viewed Apr. 21, 2008).

Thesis (Ph.D.)--Indiana University, Dept. of Kinesiology, 2007.<br>Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5772. Advisers: David M. Koceja; Dale R. Sengelaub. Title from dissertation home page (viewed May 12, 2008).

The purpose of this dissertation was to gain insight into spinal sensory regulation during locomotion. To this end, I developed a novel in vitro spinal cord-hindlimb preparation (SCHP) composed of the isolated in vitro neonatal rat spinal cord oriented dorsal-up with intact hindlimbs locomoting on a custom-built treadmill or instrumented force platforms. The SCHP combines the neural and pharmacological accessibility of classic in vitro spinal cord preparations with intact sensory feedback from physiological hindlimb movements. thereby expanding our ability to study spinal sensory function. I then validated the efficacy of the SCHP for studying behaviorally-relevant, sensory-modulated locomotion by showing the impact of sensory feedback on in vitro locomotion. When locomotion was activated by serotonin and N-methyl D-aspartate, the SCHP produced kinematics and muscle activation patterns similar to the intact rat. The mechanosensory environment could significantly alter SCHP kinematics and muscle activitation patterns, showing that sensory feedback regulates in vitro spinal function. I further demonstrated that sensory feedback could reinforce or initiate SCHP locomotion. Using the SCHP custom-designed force platform system, I then investigated how presynaptic inhibition dynamically regulates sensory feedback during locomotion and how hindlimb mechanics influence this regulation. I hypothesized that contralateral limb mechanics would modulate presynaptic inhibition on the ipsilateral limb. My results indicate that contralateral limb stance-phase loading regulates ipsilateral swing-phase sensory inflow. As contralateral stance-phase force increases, contralateral afferents act via a GABAergic pathway to increase ipsilateral presynaptic inhibition, thereby inhibiting sensory feedback entering the spinal cord. Such force-sensitive contralateral presynaptic inhibition may help preserve swing, coordinate the limbs during locomotion, and adjust the sensorimotor strategy for task-specific demands. This work has important implications for sensorimotor rehabilitation. After spinal cord injury, sensory feedback is one of the few remaining inputs available for accessing spinal locomotor circuitry. Therefore, understanding how sensory feedback regulates and reinforces spinally-generated locomotion is vital for designing effective rehabilitation strategies. Further, sensory regulation is degraded by many neural insults, including spinal cord injury, Parkinson's disease, and stroke, resulting in spasticity and impaired locomotor function. This work suggests that contralateral limb loading may be an important variable for restoring appropriate sensory regulation during locomotion.

L’inibizione presinaptica è un meccanismo di modulazione sinaptica comunemente osservato nelle sinapsi del sistema nervoso centrale e periferico. Questo processo inizia in risposta all’attivazione di un’ampia varietà di recettori presinaptici e porta ad una riduzione della probabilità di fusione delle vescicole con la membrana del terminale sinaptico. Uno dei più comuni meccanismi d’azione consiste nell’inibizione dei canali del calcio voltaggio dipendenti (VDCCs) localizzati nei bottoni presinaptici. Tuttavia, esistono altre forme di inibizione presinaptica con meccanismi che coinvolgono direttamente la machinery di rilascio vescicolare. In questa tesi ho studiato il meccanismo di inibizione presinaptica mediata dal recettore metabotropico del glutammato del tipo III (mGluRs) e dal recettore GABAB nella trasmissione GABAergica dei neuroni dopaminergici della substantia nigra pars compacta (SNc) di ratto. L’AP-4 (100 μM), agonista selettivo del recettore metabotropico del glutammato del tipo III, e il baclofen (10 μM), agonista selettivo del recettore GABAB, riducono reversibilmente la frequenza delle correnti spontanee inibitorie post-sinaptiche (sIPSCs) rispettivamente del 48.5 ± 3.7 % e del 83.6 ± 2.3 % rispetto al controllo, senza avere alcun effetto sull’ampiezza della corrente. L’AP-4, non deprime la frequenza delle correnti inibitorie miniature post-sinaptiche (mIPSCs), registrate in tetrodotossina (TTX, 1 μM) e cadmio (100 μM), mentre è in grado di ridurre la frequenza delle mIPSCs del 75.3 ± 2.8 % rispetto al controllo, in presenza di TTX (1 μM) e bario (1 mM). Al contrario, il baclofen riduce la frequenza delle mIPSCs sia in cadmio (70.0 ± 6.7 % del controllo) sia in bario (52.3 ± 2.9 % del controllo). In TTX e ionomicina (2 μM), il baclofen riduce significativamente la frequenza delle mIPSCs del 71.8 ± 6.9 % del controllo, mentre l’AP-4 non ha effetto. In maniera simile, in presenza di TTX e α-latrotossina (α-LTX, 0.3 nM), la frequenza delle mIPSCs è diminuita del 64.5 ± 4.8 % del controllo dal baclofen, mentre mantiene gli stessi valori in presenza di AP-4. Infine, in continua presenza di baclofen, l’AP-4 non causa un ulteriore riduzione della frequenza delle sIPSCs. La conclusione di questi studi è che i recettori metabotropici del glutammato del tipo III deprimono il rilascio di GABA dai neuroni dopaminergici della SNc , attraverso l’inibizione dei VDCC, mentre i recettori presinaptici GABAB coinvolgono direttamente il rilascio vescicolare del neurotrasmettitore. Inoltre questi due diversi meccanismi di inibizione pre-sinaptica coesistono nello stesso terminale sinaptico. Questa caratterizzazione fornisce nuove conoscenze sul ruolo di questi recettori presinaptici nello studio della fisiologia della substantia nigra e nel loro potenziale uso come target nel trattamento farmacologico di malattie neurodegenerative come il morbo di Parkinson.<br>Presynaptic inhibition is a mechanism of synaptic modulation normally observed in the synapses of the nervous system. This process starts upon activation of a large number of presynaptic receptors and leads to the decreased probability of vesicles to fuse to the cell membrane. One of the most common mechanism consists in the inhibition of the voltage dependent calcium channels (VDCC) located on the active zone of the presynaptic neuron. However, there is evidence for another form of presynaptic inhibition with a direct impairment of the vescicular release machinery. In my thesis I have investigated the mechanisms of presynaptic inhibition by group III metabotropic glutamate receptors (mGluRs) and GABAB receptors of the GABAergic neurotransmission to dopamine (DA) neurones of the rat substantia nigra pars compacta (SNc). The group III mGluRs agonist L-(+)-2-amino-4-phosphonobutyric acid (AP4, 100 μM) and the GABAB receptor agonist baclofen (10 μM) reversibly depressed the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) to 48.5 ± 3.7 % and 83.6 ± 2.3 % of control, respectively, with no effect in their amplitude. AP4 did not affect miniature inhibitory postsynaptic currents (mIPSCs) recorded in tetrodotoxin (TTX, 1 μM) and cadmium (100 μM), while in TTX (1 μM) and barium (1 mM), mIPSCs frequency was reduced to 75.3 ± 2.8 % of control. In contrast, baclofen reduced mIPSCs frequency either in cadmium (70.0 ± 6.7 % of control) or barium (52.3 ± 2.9 % of control). In TTX and ionomycin (2 μM), baclofen significantly reduced mIPSCs frequency to 71.8 ± 6.9 % of control, while AP4 had no effect. Similarly, in TTX and α-latrotoxin (α-LTX, 0.3 nM), the frequency of mIPSCs was reduced by baclofen to 64.5 ± 4.8 % of control, but was insensitive to AP4. Finally, in the continuous presence of baclofen, AP4 failed to produce any further reduction of sIPSCs frequency. The conclusion of this study is that group III mGluRs depress GABA release to DA neurons of the SNc through inhibition of presynaptic voltage-dependent calcium channels, while presynaptic GABAB receptors also impair transmitter exocytosis, and both mechanisms coexist on the same synapses. This characterization provides new insights about the role of these presynaptic receptors in the physiology of the substantia nigra and their potential involvement in the treatment of neurodegenerative diseases such as Parkinson’s Disease.

Antecedendo movimentos voluntariamente gerados, existe atividade neuronal encefálica que se inicia alguns segundos antes da execução deste movimento. Esta atividade preparatória é responsável pela elaboração de um plano de execução que alcança a via final comum para realização de um ato motor voluntário, os motoneurônios. Entretanto, na última década, evidências apontam para a participação de circuitos neuronais na medula espinhal apresentando padrão de atividade similar aos padrões observados em áreas encefálicas e que, possivelmente, estaria relacionado a uma atividade preparatória para o movimento voluntariamente gerado. Por este motivo, o presente trabalho teve por objetivo verificar a atividade de circuitos neuronais na medula espinhal durante diferentes instantes de proximidade da ação voluntariamente gerada em paradigma de tarefa motora com período de instrução. Para isso, inicialmente, 15 sujeitos saudáveis, sem histórico de doença neuromuscular foram submetidos ao protocolo experimental. O protocolo experimental constituiu-se do processo de recrutamento dos sujeitos, sua preparação para o ensaio dentro do ambiente experimental, bem como as orientações necessárias para execução dos procedimentos e paradigmas. Os procedimentos referem-se às etapas realizadas para captação do reflexo H, bem como desta captação sob a influência de técnica de condicionamento por inibição pré-sináptica. Essa captação ocorreu em janelas de aquisição em que o sujeito encontrava-se em repouso e em três instantes de expectativa para a execução de ação voluntária, estando o músculo sóleo atuando como agonista (flexão plantar) ou antagonista (dorsiflexão), em paradigma de tarefa motora voluntária com período de instrução. Após os registros, por meio de processamento dos sinais coletados, foi possível se calcular a amplitude pico-a-pico do reflexo H nas diferentes condições experimentais de proximidade da execução (1000, 600 e 200 milissegundos) e de atuação do músculo sóleo (agonista e antagonista) que foi usado para: (1) análise da variação da excitabilidade reflexa, em porcentagem da onda M máxima, (2) análise da ocorrência de inibição pré-sináptica e (3) análise da variação da inibição pré-sináptica, em porcentagem de inibição. Os resultados mostram que a porcentagem da onda M máxima aumentou significativamente nos três instantes de proximidade com os sujeitos estando em expectativa da execução da tarefa motora quando o músculo sóleo atuaria como agonista da contração, quando comparados com os registros obtidos nas mesmas condições em repouso. Contudo, somente a 200 ms da execução é que foi observado aumento da porcentagem da onda M máxima quando o músculo sóleo atuaria como antagonista. Inibição pré-sináptica ocorreu em todas as condições experimentais, contudo aumento significativo da porcentagem de inibição pré-sináptica foi somente observado a 200 ms da execução da tarefa motora em que o músculo sóleo atuaria como antagonista. Diferenças entre agonista e antagonista com relação ao padrão de excitabilidade reflexa foi somente observado a 600 ms de proximidade da execução da tarefa e essas diferenças com relação à porcentagem de inibição pré-sináptica foi somente detectada a 200 ms. Nossos resultados nos permitem concluir que circuitos neuronais na medula espinhal apresentam atividade no período preparatório para a execução de tarefa motora voluntária que podem estar relacionadas ao comportamento de expectativa da realização de uma ação motora eminente, bem como relacionada ao planejamento motor para a ação a longa proximidade da execução de movimentos.<br>There is brain activity preceding voluntary movements a few seconds before the execution of the movement. This preparatory activity is responsible for the execution plan that reaches the final common pathway, i.e., the motoneurons. In the last decade, there have been reports indicating the involvement of spinal cord circuits in the preparatory activity for movement. The present work has the objective of verifying the activity of spinal cord neuronal circuits at different times preceding a voluntary action, under an instructed delay period paradigm. Fifteen healthy subjects participated in the study. The protocol included an explanation of the experimental tasks. Electrophysiological recordings of the H reflex with and without presynaptic inhibition conditioning were employed. The epochs of H reflex recording were associated either with a resting period or with one of three pre-action periods. The subject received a cue at an appropriate time about the type of contraction: plantarflexion or dorsiflexion. Peak to peak H reflex values were computed in the control resting period and at 1000 ms, 600 ms and 200 ms before the action. Percent values of H amplitude with respect to maximum M values were computed as well as the level of presynaptic inhibition. The results have shown that the relative H reflex value increased significantly at the three premovement times for the soleus under an agonist contraction (i.e., plantarflexion) when compared to control. However, when the soleus was an antagonist to the contraction (i.e., dorsiflexion) there was a statistical difference in the H amplitude only at 200 ms before movement. Presynaptic inhibition occurred in all experimental conditions, however only at 200 ms before contraction there was a significant increase. Differences in reflex excitability between agonist and antagonist activity were only observed at 600 ms before action. On the other hand, differences in presynaptic inhibition were only found at 200 ms before contraction. The results indicated that spinal cord neuronal circuits are activated during the preparatory period preceding a voluntary action. These may be correlated with an expectancy behavior for the execution of an imminent motor action and also with the planning of a motor action at larger times preceding movement execution.

Introdução:As adaptações neurais ao treinamento físico vêm sendo amplamente estudadas e a medula espinhal é um dos locais de possível adaptação. No entanto nenhuma avaliação longitudinal havia sido feita diretamente sobre as circuitarias inibitórias medulares. Até o presente momento as alterações eram somente suposições. O presente trabalho verificou as circuitarias medulares responsáveis pela inibição recíproca (IR) e inibição pré-sináptica (IPS) em sujeitos submetidos a diferentes treinamentos. Materiais e Métodos: Para o treino aeróbico (resistência) foram avaliados 25 soldados submetidos ao treinamento militar do Exército Militar Brasileiro. Foram feitas 3 avaliações uma pré-treino e outras duas com 3 e 9 meses após o inicio das atividades no ano de 2006. Outros 29 sujeitos foram divididos em 3 grupos: controle (permaneceram 8 semanas sem atividades de reinamento), grupo de treino de força máxima e treino de potência. Eles foram submetidos a 8 semanas de treino, realizado com séries de agachamento livre com peso. Para avaliação das circuitarias medulares foi utilizado o reflexo H do sóleus condicionado com estímulos no nervo fibular comum (NFC) - que inerva o músculo tibial anterior (TA). O intervalo entre o estímulo condicionante e o estímulo teste determinou a avaliação da IR, da inibição D1 e da inibição D2 (IPS). Outras variáveis também foram calculadas como: contração voluntária máxima isométrica (CVM) do sóleus e TA e seus respectivos eletromiogramas (EMG), relação elétrica e mecânica entre Hmax/Mmax e condicionamento do EMG do sóleus por estímulos no NFC. Foram feitas análises pareadas com teste t-student para o grupo militar e ANOVA two-way para comparação dos grupos de força máxima e potência com o grupo controle. Principais Resultados: O grupo do exército apresentou aumento na força do sóleus e do TA, juntamente com aumento no RMS do EMG do sóleus e do torque gerado pela onda Mmax, sem alterações nos relações Hmax/Mmax. O treinamento militar reduziu significativamente a inibição D1 e mostrou tendências a aumento da IPS. O grupo de força máxima não mostrou aumento de força isométrica, no entanto apresentou aumento na relação elétrica Hmax/Mmax, com concomitante redução da IR e aumento da IPS. O grupo de potência mostrou ganho na força máxima isométrica somente do sóleus. A capacidade de gerar torque reflexamente também aumentou neste grupo, com aumento significativo na relação mecânica Hmax/Mmax. Esta melhora na utilização do arco reflexo também foi verificada com redução da IPS e aumento da IR neste grupo.Conclusões: Estes resultados mostraram que a medula espinal sofre plasticidade nas vias inibitórias IR, inibição D1 e D2, e que esta plasticidade é dependente do tipo de tarefa realizada.<br>Introduction: Neural adaptations with physical training have been widely studied. The spinal cord is a possible locus of adaptation. However, longitudinal studies that evaluate directly the spinal cord pathways have not been found in the literature. Therefore, all reports from the literature justify changes found in measured responses to exercise by hypotheses on spinal cord mechanisms. This study had the objective of measuring features of specific spinal cord pathways to check if they change according to the type of physical training. The pathways related to reciprocal inhibition (RI) and pre-synaptic inhibition (PSI) were investigated in subjects undergoing different trainings. Materials and Methods: For endurance training 25 soldiers were subjected to military training of the Brazilian Army. Evaluations were made three times, one previous to the beginning of the activity and twice post-training (within 3 and 9 months). Other 29 subjects were divided into: control group (with no training), maximal strength group and power group. They were subjected to 8 weeks of training with series of squat movements. The soleus H reflex conditioning with stimuli in the common peroneal nerve (CPN) was used to evaluate the spinal cord pathways. The interval between the conditioning and the test stimulus determine the assessment of RI, D1 inhibition and D2 inhibition (PSI). Other variables were also calculated: maximum voluntary isometric contraction from soleus and tibialis anterior and their electromyograms (EMG), electrical and mechanical Hmax/Mmax ratio and 3 inhibitions over the soleus EMG conditioned by stimuli to the CPN. The results were analyzed with paired t-student test for the military group and with two-way ANOVA to compare the maximal strength and power groups with the control group. Main Results: The military group had increased strength of the soleus and the TA muscles, with an increase in the RMS of the soleus EMG. This group also increased the torque generated by the Mmax-wave, without changes in Hmax/Mmax ratio. The military training significantly reduced D1 inhibition and showed tendencies to increase the PSI. The maximal strength group showed no differences in isometric strength, but had increased Hmax/Mmax ratio with concomitant reduction of RI and increased PSI. The power group increased isometric strength only for the soleus muscle. This group also improved the ability to generate torque by reflex pathways, with significant increase in the mechanical Hmax/Mmax ratio, with a reduction of PSI and increase of RI. Conclusions: These results show that spinal cord plasticity occurs in the inhibitory pathways of reciprocal inhibition, D1 inhibition and D2 inhibition (pre-synaptic inhibition), and that plasticity is dependent on the type of trained movement.

The central nervous system is largely responsible for receiving sensory information from the environment and determining motor output. Yet, centrally-derived behavior and sensation depends on the optimal maintenance of the cells, tissues, and organs that feed and support these functions. Most of visceral regulation occurs without conscious oversight, making the spinal cord a key site for integration and control. How the spinal cord modulates output to our organs, or sensory information from them, is poorly understood. The overall aim of this dissertation was to better understand spinal processing of both visceral sensory information to and sympathetic output from the spinal cord. I first established and validated a HB9-GFP transgenic mouse model that unambiguously identified sympathetic preganglionic neurons (SPNs), the spinal output neurons for the sympathetic nervous system. Using this model, I investigated the electrophysiological similarities and diversity of SPNs, and compared their active and passive membrane properties to those in other animal models. My results indicate that while many of the same characteristics are shared, SPNs are a heterogeneous group that can be differentiated based on their electrophysiological properties. Since descending monoaminergic pathways have particularly dense projections to sympathetic regions of the spinal cord, I next examined the modulatory role that the monoamines have on spinal sympathetic output. While each neuromodulator tested had a unique signature of action, serotonin and norepinephrine appeared to increase the excitability of individual SPNs, while dopamine had more mixed actions. Since many autonomic reflexes are integrated by the spinal cord, I also questioned whether these reflexes would be similarly modulated. I therefore developed a novel in vitro spinal cord and sympathetic chain preparation, which allowed for the investigation of visceral afferent-mediated reflexes and their neuromodulation by monoamines. This preparation exposed a dichotomy of action, where sympathetic and somatic motor output is generally enhanced by the monoamines, but reflexes mediated by visceral input are depressed. Utilizing the spinal cord and sympathetic chain preparation, I also investigated how the spinal cord modulates visceral sensory information. One of the most powerful means of selectively inhibiting afferent information from reaching the spinal cord is presynaptic inhibition. I hypothesized that both spinal visceral afferents and descending monoaminergic systems would depress transmission of visceral afferents to the spinal cord. My results demonstrated that activity in spinal visceral afferents can lead to spinally generated presynaptic inhibition, and that in addition to depressing synaptic transmission to the spinal cord, the monoamines also depress the intrinsic circuitry that generates this activity-dependent presynaptic inhibition. Taken together, my results indicate that descending monoaminergic pathways act to limit the amount of visceral sensory information reaching the central nervous system and increase sympathetic output, resulting in an uncoupling of output from visceral sensory input and transitioning to a feed-forward, sympathetically dominant control strategy. This combination offers complex modulatory strategies for descending systems.

The precision of mammalian movement relies on excitatory sensory feedback supplied by proprioceptors, and its context-dependent refinement by spinal inhibitory microcircuits. One microcircuit that has been implicated in the regulation of sensory input establishes inhibitory synapses directly on the central terminals of sensory neurons. To date, however, the difficulty in gaining selective access to discrete classes of inhibitory interneurons within local microcircuits has left unresolved the contribution of presynaptic inhibition, if any, to motor behavior. Here we have used mouse genetics to gain access to the set of GABAergic interneurons that provide direct input to sensory terminals, and show that their activation evokes the defining physiological features of presynaptic inhibition. Genetic ablation of this set of interneurons in the adult severely perturbs goal-directed reaching movements, and uncovers a pronounced forelimb motor oscillation that appears to have its basis in an enhancement in the gain of sensory feedback. Together, our findings uncover an essential motor behavioral role for this specialized set of presynaptic inhibitory interneurons, and emphasize the relevance of sensory gain control in the neural programming of skilled movement.

During rhythmic arm cycling soleus H-reflex amplitudes are reduced by modulation of group Ia presynaptic inhibition (Frigon et al, 2004). This reflex suppression is graded with the frequency of arm cycling (Loadman & Zehr 2007; Hundza & Zehr 2009) and 0.8 Hz is the minimum frequency to significantly reduce the soleus H-reflex (Hundza & Zehr 2009). Despite the data on modulation of the soleus H-reflex amplitude induced by rhythmic arm cycling, comparatively little is known about the modulation of stretch reflexes due to remote limb movement. Therefore, the present study was intended to explore the effect of arm cycling on stretch and H-reflex amplitudes in the soleus muscle. In so doing, additional information on the mechanism of action during rhythmic arm cycling would be revealed. Although both reflexes share the same afferent pathway, we hypothesized that stretch reflex amplitudes would be less suppressed by arm cycling because they are less inhibited by presynaptic inhibition (Morita et al, 1998). Failure to reject this hypothesis would add additional strength to the argument that Ia presynaptic inhibition is the mechanism modulating soleus H-reflex amplitude during rhythmic arm cycling. Participants were seated in a customized chair with feet strapped to footplates. Three motor tasks were performed: static control trials and arm cycling at 1 and 2 Hz. Soleus H-reflexes were evoked using single 1 ms pulses of electrical stimulation delivered to the tibial nerve at the popliteal fossa. A constant M-wave and ~6% MVC activation of soleus was maintained across conditions. Stretch reflexes were evoked using a vibratory shaker (ET-126; Labworks Inc). The shaker was placed over the triceps surae tendon and controlled by a custom written LabView program (single sinusoidal pulse at 100Hz). Results demonstrated that rhythmic arm cycling that was effective for conditioning soleus H-reflexes did not show a suppressive effect on the amplitude of the soleus stretch reflex. We suggest this indicates that stretch reflexes are less sensitive to conditioning by rhythmic arm movement, as compared to H-reflexes, due to the relative insensitivity of Ia presynaptic inhibition.<br>Graduate

博士<br>國立陽明大學<br>神經科學研究所<br>102<br>The dentate gyrus (DG) serves as a primary gate to control information transfer from the cortex to the hippocampus. Activation of incoming cortical inputs results in rapid synaptic excitation followed by slow γ-aminobutyric acid-mediated (GABAergic) synaptic inhibition onto DG granule cells (GCs). GABAergic inhibitory interneurons (INs) in the DG comprise fast-spiking (FS) and non-fast-spiking (non-FS) cells. Anatomical analyses of DG INs reveal that FS cells are soma-targeting INs, whereas non-FS cells are dendrite-targeting INs. These two IN classes are differentially recruited by excitatory inputs and in turn provide exquisite spatiotemporal control over GC activity. Yet, little is known how FS and non-FS cells transform their presynaptic dynamics into varying postsynaptic response amplitudes. Using paired recordings in rat hippocampal slices, I show that inhibition in the DG is dominated by somatic GABAergic inputs during periods of sparse presynaptic activity, whereas dendritic GABAergic inputs are rapidly shifted to powerful and sustained inhibition during periods of intense presynaptic activity. The variant dynamics of dendritic inhibition is dependent on presynaptic IN subtypes and their activity patterns and is attributed to Ca2+-dependent increases in the probability of release and the size of the readily releasable pool. Furthermore, the degree of dynamic GABA release can be reduced by blocking voltage-gated K+ channels, which increases the efficacy of dendrite-targeting IN output synapses during sparse firing. Such rapid dynamic modulation of dendritic inhibition may act as a frequency-dependent filter to prevent over-excitation of GC dendrites and thus set the excitatory-inhibitory synaptic balance in the DG circuits.

Despite years of research, females continue to have a higher incidence of non-contact ACL injuries. One of the major findings of this research is that males and females perform certain tasks, such as, cutting, landing, and single-leg squatting, differently. In particular, females tend to move the knee into a more valgus position; a motion putting the ACL at risk for injury. Yet the underlying spinal control mechanisms modulating this motion are unknown. Additionally, the mechanisms regulating the ability to rapidly initiate and produce maximal torque are also unknown. Therefore, the purpose was to: 1) determine if the sexes modulate spinal control differently, 2) examine the contributions of spinal control mechanisms to valgus knee motion, and 3) identify contributions of spinal control to the ability to rapidly produce force. The spinal control variables were the first derivative of the Hoffmann (H)-reflex, the first derivative of extrinsic pre-synaptic inhibition (EPI), the first derivative of intrinsic pre-synaptic inhibition (IPI), recurrent inhibition (RI), and V-waves. To assess the neuromuscular system’s ability to rapidly activate, rate of torque development (RTD) and electromechanical delay (EMD) were measured. Lastly, valgus motion was determined by the frontal plane projection angle (FPPA). The results reveal males and females do modulate spinal control differently; specifically males had an increased RTD, which is the slope of the torque-time curve, and increased RI, which is a post-synaptic regulator of torque output. However, the spinal control mechanisms did not significantly contribute to FPPA at the knee. EMD which is the time lag from muscle activity to torque production was significantly predicted by the spinal control mechanisms. Specifically, EPI, a modulator of afferent inflow from peripheral and descending sources, IPI, a regulator of Ia afferent inflow, and sex significantly contributed to EMD. Lastly, the spinal control mechanisms significantly contributed to RTD. Specifically, IPI, sex, and V-waves, a measure of supraspinal drive, all significantly contributed to RTD.<br>Graduation date: 2009

Le risque de chute est une problématique bien présente chez les personnes âgées ou ayant une atteinte neurologique et reflète un déficit des mécanismes neuronaux assurant l’équilibre. De précédentes études démontrent que l’intégration des informations sensorielles est essentielle au contrôle de l’équilibre et que l’inhibition présynaptique (IP) serait un mécanisme important dans le contrôle de la transmission sensorielle. Ainsi, le but de cette étude était d’identifier la contribution du mécanisme d’IP à l’induction de réponses posturales efficaces suite à une perturbation d’équilibre. Notre hypothèse est qu’une diminution d’IP contribuerait à l’induction des ces réponses, en augmentant l’influence de la rétroaction sensorielle sur les réseaux de neurones spinaux. Afin de démontrer cette hypothèse, nous avons d’abord évalué l’excitabilité spinale pendant les perturbations vers l’avant ou vers l’arrière, à l’aide du réflexe H. L’excitabilité spinale était modulée selon la direction de la perturbation et cette modulation survenait dès 75 ou 100 ms (p<0.05), soit avant l’induction des réactions posturales. Puis, à l’aide de techniques plus précises de convergence spinale, nous avons démontré que l’IP était diminuée dès 75 et 100 ms dans les deux directions, suggérant que la transmission des informations sensorielles vers la moelle épinière est accrue juste avant le déclenchement de la réponse posturale. Cette étude met en évidence un mécanisme-clé permettant d’augmenter la rétroaction des informations sensorielles nécessaires à l’induction de réponses posturales appropriées. L’évaluation de ce mécanisme pourrait mener à une meilleure identification des individus à risque de chute.<br>Falls are a significant problem among the elderly or persons with a neurological impairment, and reflect a deficit in the nervous mechanisms underlying postural control. Previous research shows that the integration of sensory feedback is a crucial component of postural control and that presynaptic inhibition (PSI) plays an important role in controlling the sensory processing of information. The aim of this study was to identify the contribution of PSI to the induction of effective postural responses following an unexpected balance perturbation. We hypothesized that a decrease in PSI would contribute to the induction of these responses by increasing the influence of sensory feedback onto spinal networks during the perturbation. First we assessed the level of spinal excitability during perturbations, using the soleus H-reflex. Results show that spinal excitability is modulated according to the direction of the perturbation (forward and backward tilts) and that this modulation occurs 75 and 100 ms after tilt-onset in all subjects (p<0.05). To further estimate changes in PSI, spatial facilitation techniques were used. PSI was shown to decrease in both perturbation directions shortly after tilt onset at 75 and 100 ms (p<0.05), suggesting an increase in sensory transmission in the spinal cord. These observations suggest that sensory feedback is critical for the induction of effective postural responses and that impaired sensory transmission or integration, due to CNS lesions or ageing, may lead to certain balance deficits. Identifying patients with such impairments may improve fall risk-assessment and prevention.