biostudies-literatureHe LNICHD NIH HHSHoward Hughes Medical InstituteNIMH NIH HHSNINDS NIH HHS1689-1699.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC9930308biostudies-literatureUnknown110(10)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 byNeuronA weakened recurrent circuit in the hippocampus of Rett syndrome mice disrupts long-term memory representations.PMC9930308R01 NS100738R01 NS057819R01 MH120404R01 NS110767P50 HD103555R56 NS100738R01 MH122169Tang JJing JZoghbi HYCaudill MSJiang XWang WHe LSun YfalseA weakened recurrent circuit in the hippocampus of Rett syndrome mice disrupts long-term memory representations.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 by2022-01-01T00:00:00Z2022 May2026-05-29T13:58:59.885Z2025-02-19T03:25:54.828ZS-EPMC99303083529079210.1016/j.neuron.2022.02.014