Bidirectional regulation of distinct memory domains by α5-subunit-containing GABAA receptors in CA1 pyramidal neurons
- 1Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, Massachusetts 02478, USA
- 2Stress Neurobiology Laboratory, McLean Hospital, Belmont, Massachusetts 02478, USA
- 3Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02215, USA
- 4Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland
- 5Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA
- 6Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA
- Corresponding author: eengin{at}mclean.harvard.edu
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.
Footnotes
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.052084.120.
- Received June 2, 2020.
- Accepted July 2, 2020.
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