A Weakened Recurrent Circuit in the Hippocampus of Rett Syndrome Mice Disrupts Long-Term Memory Representations

Authors

Lingjie He
Matthew S Caudill
Junzhan Jing
Wei Wang
Yaling Sun
Jianrong Tang
Xiaolong Jiang
Huda Y Zoghbi

Publication Date

5-18-2022

Journal

Neuron

DOI

10.1016/j.neuron.2022.02.014

PMID

35290792

PMCID

PMC9930308

PubMedCentral® Posted Date

5-18-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Hippocampus, Interneurons, Memory Disorders, Memory, Long-Term, Mice, Pyramidal Cells, Rett Syndrome

Abstract

Successful recall of a contextual memory requires reactivating ensembles of hippocampal cells that were allocated during memory formation. Altering the ratio of excitation-to-inhibition (E/I) during memory retrieval can bias cell participation in an ensemble and hinder memory recall. In the case of Rett syndrome (RTT), a neurological disorder with severe learning and memory deficits, the E/I balance is altered, but the source of this imbalance is unknown. Using in vivo imaging during an associative memory task, we show that during long-term memory retrieval, RTT CA1 cells poorly distinguish mnemonic context and form larger ensembles than wild-type mouse cells. Simultaneous multiple whole-cell recordings revealed that mutant somatostatin expressing interneurons (SOM) are poorly recruited by CA1 pyramidal cells and are less active during long-term memory retrieval in vivo. Chemogenetic manipulation revealed that reduced SOM activity underlies poor long-term memory recall. Our findings reveal a disrupted recurrent CA1 circuit contributing to RTT memory impairment.