Modeling the Contributions of the Exocytotic Machinery and Receptor Desensitization to Short- and Long-Term Plasticity of Synapses Between Neocortical Pyramidal Neurons
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Abstract
Short-term synaptic depression (STD) refers to the progressive decrease in synaptic efficacy during a spike train. This decrease may be explained in terms of presynaptic and postsynaptic processes, such as a decrease in the probability of transmitter release, and postsynaptic receptor desensitization. STD may be very strong, and is release-dependent in neocortical pyramid-pyramid synapses. Using a stochastic synapse model, we suggest that the main source of depression in these synapses is the step of vesicle priming, while vesicle depletion and postsynaptic receptor desensitization are proposed to play a lesser role. Our results suggest that vesicle priming may explain not only the release-dependent nature of STD, but also the observation that an average of about one vesicle per active zone is released in central synapses, without positing forced univesicular release. We propose that the latter phenomenon is due to a low priming probability. Our results also explain the effect of paired pre- and postsynaptic activity on STD. In neocortical pyramid-pyramid synapses pairing induces a form of long-term potentiation that has been described as a redistribution of synaptic efficacy (RSE). We propose that RSE is due to a pairing-induced increase in the probability that a primed vesicle will undergo release in response to a presynaptic action potential. This increase may be due to an increased Ca^2+ influx through voltage-gated Ca^2+ channels, or to an increased sensitivity of primed vesicles to this influx. The results were obtained by constraining the model with experimentally observed levels of release probability and other synaptic variables.
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Copyright 2001 Boston University. Permission to copy without fee all or part of this material is granted provided that: 1. The copies are not made or distributed for direct commercial advantage; 2. the report title, author, document number, and release date appear, and notice is given that copying is by permission of BOSTON UNIVERSITY TRUSTEES. To copy otherwise, or to republish, requires a fee and / or special permission.