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Reduction in the expression or function of α5-subunit-containing GABA A  receptors (α5GABA A Rs) leads to improvement in several hippocampus-dependent memory domains. However, studies thus far mostly lack anatomical specificity in terms of neuronal circuits and populations. We demonstrate that mice with a selective knockdown of α5GABA A Rs in CA1 pyramidal neurons (α5CA1KO mice) show improved spatial and trace fear-conditioning memory. Unexpectedly, α5CA1KO mice were comparable to controls in contextual fear-conditioning but showed an impairment in context discrimination, suggesting fine-tuning of activity in CA1 pyramidal cell dendrites through α5-mediated inhibition might be necessary for distinguishing highly similar contexts.

Bidirectional regulation of distinct memory domains by α5-subunit-containing GABAA receptors in CA1 pyramidal neurons

Bidirectional regulation of distinct memory domains by α5-subunit-containing GABA_A receptors in CA1 pyramidal neurons