A weakened recurrent circuit in the hippocampus of Rett syndrome mice disrupts long-term memory representations

Neuron. 2022 May 18;110(10):1689-1699.e6. doi: 10.1016/j.neuron.2022.02.014. Epub 2022 Mar 14.


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.

Keywords: E/I balance; Rett syndrome; inhibition; memory retrieval; neural ensemble; somatostatin cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / physiology
  • Interneurons / physiology
  • Memory Disorders / genetics
  • Memory, Long-Term
  • Mice
  • Pyramidal Cells / physiology
  • Rett Syndrome* / genetics