A biochemical description of postsynaptic plasticity-with timescales ranging from milliseconds to seconds.
Proc Natl Acad Sci U S A
; 121(7): e2311709121, 2024 Feb 13.
Article
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| MEDLINE
| ID: mdl-38324573
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 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 [Formula see text] 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 [Formula see text] flow through CaV1.3 channels. Once in the spine head, this small additional [Formula see text] opens the compact state of CaMKII, placing CaMKII ready for subsequent induction of LTP.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina
/
Plasticidad Neuronal
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2024
Tipo del documento:
Article