Geon The Mechanism of Memory Extinction Papers



The memory of an event is encoded in an ensemble of "memory units", which are likely to be the dendritic branches, rather than individual synapses or spines. Thus, the membrane potential resulting from synchronous opening of NMDA receptors (NMDARs) in dendritic branches, known as NMDA spike or plateau, should make important contribution to the macroscopic state of a memory. This paper shows that the macroscopic memory of an event could be determined by the microscopic states of NMDARs involved in the generation of NMDA spike/plateau. Regarding memory extinction and retrieval, a GluN2B-containing NMDAR can have three distinct states: resting, open and extinction, but the extinction state does not exist in GluN2A-containing NMDARs because the tubulin/CRMP2 complex binds only to GluN2B, not GluN2A. Therefore, a large GluN2B/GluN2A ratio is prone to memory extinction. Sine BDNF promotes the localization of GluN2B-containing NMDARs to dendritic membrane, this explains why BDNF enhances extinction. Dopamine has also been shown to enhance extinction. Its underlying mechanism can be explained by the Tubulin Inhibition Hypothesis which posits that the memory extinction and retrieval are fundamentally governed by the competition between protein kinase A and calcineurin for the phosphorylation state of S1166 in GluN2B.


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