title: Moderate AMPA receptor clustering on the nanoscale can efficiently potentiate synaptic current.
abstract: The prevailing view at present is that postsynaptic expression of the classical NMDA receptor-dependent long-term potentiation relies on an increase in the numbers of local AMPA receptors (AMPARs). This is thought to parallel an expansion of postsynaptic cell specializations, for instance dendritic spine heads, which accommodate synaptic receptor proteins. However, glutamate released into the synaptic cleft can normally activate only a hotspot of low-affinity AMPARs that occur in the vicinity of the release site. How the enlargement of the AMPAR pool is causally related to the potentiated AMPAR current remains therefore poorly understood. To understand possible scenarios of postsynaptic potentiation, here we explore a detailed Monte Carlo model of the typical small excitatory synapse. Simulations suggest that approximately 50% increase in the synaptic AMPAR current could be provided by expanding the existing AMPAR pool at the expense of 100-200% new AMPARs added at the same packing density. Alternatively, reducing the inter-receptor distances by only 30-35% could achieve a similar level of current potentiation without any changes in the receptor numbers. The NMDA receptor current also appears sensitive to the NMDA receptor crowding. Our observations provide a quantitative framework for understanding the 'resource-efficient' ways to enact use-dependent changes in the architecture of central synapses.
authors.affiliation: UCL Institute of Neurology, University College London, , Queen Square, London WC1N 3BG, UK.
authors.forename: Leonid P
authors.initials: LP
authors.lastname: Savtchenko
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Rusakov
mesh_terms: D003198:Computer Simulation; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008959:Models, Neurological; D009010:Monte Carlo Method; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D018698:Glutamic Acid
keywords: AMPA receptor; NMDA receptor; long-term potentiation