A biochemical description of postsynaptic plasticity—with timescales ranging from milliseconds to seconds

Guanchun Li, David W. McLaughlin, Charles S. Peskin

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Synaptic plasticity [long-term potentiation/depression (LTP/D)], is a cellular mechanism underlying learning. Two distinct types of early LTP/D (E-LTP/D), acting on very different time scales, have been observed experimentally—spike timing dependent plasticity (STDP), on time scales of tens of ms; and behavioral time scale synaptic plasticity (BTSP), on time scales of seconds. BTSP is a candidate for a mechanism underlying rapid learning of spatial location by place cells. Here, a computational model of the induction of E-LTP/D at a spine head of a synapse of a hippocampal pyramidal neuron is developed. The single-compartment model represents two interacting biochemical pathways for the activation (phosphorylation) of the kinase (CaMKII) with a phosphatase, with ion inflow through channels (NMDAR, CaV1,Na). The biochemical reactions are represented by a deterministic system of differential equations, with a detailed description of the activation of CaMKII that includes the opening of the compact state of CaMKII. This single model captures realistic responses (temporal profiles with the differing timescales) of STDP and BTSP and their asymmetries. The simulations distinguish several mechanisms underlying STDP vs. BTSP, including i) the flow of Ca2+ through NMDAR vs. CaV1 channels, and ii) the origin of several time scales in the activation of CaMKII. The model also realizes a priming mechanism for E-LTP that is induced by Ca2+ flow through CaV1.3 channels. Once in the spine head, this small additional Ca2+ opens the compact state of CaMKII, placing CaMKII ready for subsequent induction of LTP.

Original languageEnglish (US)
Article numbere2311709121
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 13 2024


  • BTSP
  • STDP
  • long-term depression
  • long-term potentiation
  • synaptic plasticity

ASJC Scopus subject areas

  • General


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