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Bidirectional regulation of distinct memory domains by α5-subunit-containing GABA$_{A}$ receptors in CA1 pyramidal neurons


Engin, Elif; Sigal, Maksim; Benke, Dietmar; Zeller, Anja; Rudolph, Uwe (2020). Bidirectional regulation of distinct memory domains by α5-subunit-containing GABA$_{A}$ receptors in CA1 pyramidal neurons. Learning & memory (Cold Spring Harbor, N.Y.), 27(10):423-428.

Abstract

Reduction in the expression or function of α5-subunit-containing GABAA receptors (α5GABAARs) 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 α5GABAARs 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.

Abstract

Reduction in the expression or function of α5-subunit-containing GABAA receptors (α5GABAARs) 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 α5GABAARs 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.

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Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Social Sciences & Humanities > Neuropsychology and Physiological Psychology
Life Sciences > Cognitive Neuroscience
Life Sciences > Cellular and Molecular Neuroscience
Language:English
Date:October 2020
Deposited On:22 Oct 2020 08:34
Last Modified:27 Jan 2022 02:49
Publisher:Cold Spring Harbor Laboratory Press
ISSN:1072-0502
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/lm.052084.120
PubMed ID:32934095

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