Phosphorylation of PSD-95 at serine 73 in dCA1 is required for extinction of contextual fear

PLoS Biol. 2023 May 8;21(5):e3002106. doi: 10.1371/journal.pbio.3002106. eCollection 2023 May.

Abstract

The updating of contextual memories is essential for survival in a changing environment. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular mechanisms of contextual fear memory updating remain poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic manipulations in vivo, combined with ex vivo 3D electron microscopy and electrophysiology, we identify a novel, synaptic mechanism that is induced during attenuation of contextual fear memories and involves phosphorylation of PSD-95 at Serine 73 in dCA1. Our data provide the proof that PSD-95-dependent synaptic plasticity in dCA1 is required for updating of contextual fear memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disks Large Homolog 4 Protein / metabolism
  • Fear* / physiology
  • Hippocampus / metabolism
  • Neuronal Plasticity*
  • Phosphorylation
  • Synapses / metabolism

Substances

  • Disks Large Homolog 4 Protein

Grants and funding

This work was supported by a National Science Centre (Poland) (Grant SONATA BIS No. 2015/19/B/NZ4/02996 and grant MAESTRO No. 2020/38/A/NZ4/00483 to KR; Grant PRELUDIUM No. 2016/21/N/NZ4/03304 to MZ; Grant PRELUDIUM No. 2015/19/N/NZ4/03611 to KŁ; Grant PRELUDIUM No. 2019/35/N/NZ4/01910 to KFT; Grant SONATA BIS No. 2017/26/E/NZ4/00637 to JW; Grant SONATA BIS No. 2019/34/E/NZ4/00387 to TW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.