title: Synapse geometry and receptor dynamics modulate synaptic strength.
abstract: Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD) and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity.
authors: Department of Mathematics and Department of Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
authors: Dominik
authors: D
authors: Freche
authors: Ulrike
authors: U
authors: Pannasch
authors: Nathalie
authors: N
authors: Rouach
authors: David
authors: D
authors: Holcman
mesh_terms: D000200:Action Potentials; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D018091:Receptors, AMPA; D018698:Glutamic Acid