Plasticité présynaptique et gliale à long-terme en réponse à un changement chronique de l’activité synaptique,à la jonction neuromusculaire d’amphibien
Synaptic plasticity is a major property of the nervous system, believed to be at the basis of neuronal information processing.  This plasticity has been generally described with pre and postsynaptic adaptations.  Notably, presynaptic efficacy, referring to the probability of transmitter release associated with the quantal content of a synapse, can be increased or decreased according to the previous history of synapses.  Despite this characterization, the mechanisms implicated in the activity-dependent determination of synaptic efficacy remain unknown.  Moreover, synaptic plasticity has never been described in terms of glial adaptations, thus limiting our comprehension of neuronal information processing.  Nevertheless, the past decade has lead to a redefinition of glial cells functions. Relegated to a passive role of neuronal support in the past, glial cells are now known to be involved in the regulation of neurotransmission.  For instance, at the neuromuscular junction (NMJ), perisynaptic Schwann cells (PSCs) are believed to modulate synaptic efficacy and plasticity.  Such an active role requires, however, that PSCs adapt to the changing needs of NMJs.  Thus, synaptic plasticity must underlie glial plasticity.  At the NMJ, changes in synaptic activity result in several morphological and physiological adaptations.   Among others, chronic nerve stimulation was shown to decrease synaptic efficacy and short-term depression.  Conversely, chronic blockade of postsynaptic nicotinic receptors increases synaptic efficacy.  Given that PSCs can detect and respond to neurotransmission with a calcium elevation and that they react to environmental stimuli with morphological, physiological and gene expression adaptations, we propose that prolonged changes in synaptic efficacy, induced by chronic nerve stimulation or chronic blockade of nicotinic receptors, would lead to PSCs adaptations.  Thus, in this thesis, we studied, in parallel, long-term presynaptic and glial plasticity, in response to chronic changes in synaptic activity, at the amphibian NMJ.   Our results show presynaptic adaptations of synaptic efficacy, short-term plasticity, mitochondrial content and calcium signalling.  They also reveal several adaptations of PSCs, related to their sensitivity to neurotransmitters and their calcium responses properties.  These presynaptic and glial adaptations are discussed, in parallel, in terms of possible mechanisms and functions in the regulation of neurotransmission.  Our work also confirms the coincidence of presynaptic and glial plasticity and, therefore, raises the importance of glial adaptations for the maintenance of synaptic function.
Mitochondries Frequenine Perisynaptic Schwann cell Neuromuscular junction Synaptic plasticity Synaptic depression Post-tetanic potentiation Mitochondria Frequenin Chronic nerve stimulation Chronique blockade of nicotinic receptors Calcium imaging