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

Elif Engin; Maksim Sigal; Dietmar Benke; Anja Zeller; Uwe Rudolph

doi:10.1101/lm.052084.120

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

Elif Engin, Maksim Sigal, Dietmar Benke, Anja Zeller, Uwe Rudolph

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	423-428
Number of pages	6
Journal	Learning & memory (Cold Spring Harbor, N.Y.)
Volume	27
Issue number	10
DOIs	https://doi.org/10.1101/lm.052084.120
State	Published - Oct 2020

ASJC Scopus subject areas

Neuropsychology and Physiological Psychology
Cellular and Molecular Neuroscience
Cognitive Neuroscience

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10.1101/lm.052084.120

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

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.",

author = "Elif Engin and Maksim Sigal and Dietmar Benke and Anja Zeller and Uwe Rudolph",

note = "Funding Information: This work was supported by award numbers R01GM086448 (U.R.), R01GM128183 (U.R.), and K01MH107787 (E.E.). In the last 2 years, U.R. has served as a consultant for Concert Pharmaceuticals. We thank Dr. Susumu Tonegawa (HHMI, Massachusetts Institute of Technology) for providing the T29-1 mice.",

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doi = "10.1101/lm.052084.120",

language = "English (US)",

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AU - Engin, Elif

AU - Sigal, Maksim

AU - Benke, Dietmar

AU - Zeller, Anja

AU - Rudolph, Uwe

N1 - Funding Information: This work was supported by award numbers R01GM086448 (U.R.), R01GM128183 (U.R.), and K01MH107787 (E.E.). In the last 2 years, U.R. has served as a consultant for Concert Pharmaceuticals. We thank Dr. Susumu Tonegawa (HHMI, Massachusetts Institute of Technology) for providing the T29-1 mice.

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N2 - 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.

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

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