Imagerie en molécules uniques de la diffusion des récepteurs au glutamate dans les synapses et leur implication dans la plasticité synaptique
|Advisor:||Boudreau, Denis; De Koninck, Paul|
|Abstract:||The AMPA receptor (AMPAR) is a subtype of glutamate receptor responsible for the majority of fast excitatory synaptic transmission in the central nervous system. The addition of new receptors to the membrane by exocytosis and redistribution of AMPARs at the postsynaptic site have been proposed as mechanisms of long-term potentiation (LTP) of synaptic transmission, a cellular model of learning and memory. Direct evidence supporting these predictions is missing and the molecular mechanisms that regulate the contribution of AMPARs in the membrane traffic at synapses are poorly understood. To study the mechanisms of redistribution of AMPARs at synapses, we developed a high resolution single molecule imaging technique. We provide direct evidence that local activation of α subunit of the Ca2+/calmodulin protein kinase II (αCaMKII) triggers the rapid immobilization of AMPARs to synaptic sites. In addition, we found that phosphorylation of the auxiliary subunit of AMPARs, stargazine, is required for immobilization at synapses by binding to the synaptic scaffolding protein, PSD-95. Also, in a second study, we have highlighted the distinct contributions of two different isoforms α and β of CaMKII under conditions of basal transmission and following stimuli that induce synaptic plasticity. Our studies provide new insights on the mechanism underlying LTP. To study the contribution of new receptors to the membrane, we use receptors fused to pH-sensitive fluorescent proteins, we measured the discrete exocytic fusion events of GluA1 to the postsynaptic membrane. We provide evidence that CaMKII regulates the process of AMPAR exocytosis. Our experiments contribute to the understanding of how CaMKII, an important enzyme in memory, can regulate the increased delivery of AMPARs at synapses during synaptic potentiation, via their increased exocytosis and post-synaptic trapping.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||19 April 2018|
|Collection:||Thèses et mémoires|
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