A Biochemical Description of Postsynaptic Plasticity – with Timescales Ranging from Milliseconds to Seconds

Abstract

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 plasticity(BTSP), on time scales of seconds. BTSP is a candidate for the mechanism for rapid learning of spatial location by hippocampal 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 described by NMDAR, CaV1, and Na channels. The biochemical reactions are represented by a deterministic system of differential equations. This single model captures realistic responses (temporal profiles with the differing timescales) of STDP and BTSP and their asymmetries for each (STDP or BTSP) signaling protocol. The simulations detail several mechanisms underlying both STDP and BTSP, including i) the flow ofCa2+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 byCa2+flow through CaV1.3 channels. Once in the spine head, this small additionalCa2+opens the compact state of CaMKII, placing CaMKII “in the ready” for subsequent induction of LTP.