Zn²⁺ inhibits spatial memory and hippocampal place cell representation through high-affinity binding to the NMDA receptor GluN2A subunit.

ABSTRACT: A subset of glutamatergic neurons in the forebrain uses labile Zn²⁺ as a co-transmitter alongside glutamate. Synaptic Zn²⁺ plays a key role in learning and memory processes, but its mechanisms of action remain poorly understood. Here, we used a knock-in (KI) mouse line carrying a point mutation at the GluN2A Zn²⁺ binding site that selectively eliminates zinc inhibition of NMDA receptors. Ablation of Zn²⁺-GluN2A binding improves spatial memory retention and contextual fear memory formation. Electrophysiological recording of hippocampal neurons in the CA1 area revealed a greater proportion of place cells and substantial place field remapping in KI mice compared to wildtype littermates. Persistent place cell remapping was also seen in KI mice upon r

SUBMITTER: Sikora J 

PROVIDER: S-EPMC9619178 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature