The Role of the δ GABA(A) Receptor in Ovarian Cycle-Linked Changes in Hippocampus-Dependent Learning and Memory
Open accessAbstract
The δ subunit of the GABAAR is highly expressed in the dentate gyrus of the hippocampus where it mediates a tonic extrasynaptic inhibitory current that is sensitive to neurosteroids. In female mice, the expression level of the δ subunit within the dentate gyrus is elevated in the diestrous relative to estrous phase of the estrous cycle. Previous work in our lab found that female δ-GABAAR KO mice showed enhanced hippocampus-dependent trace but normal hippocampus-independent delay fear conditioning. Wild-type females in this study showed a wide range of freezing levels, whereas δ-GABAAR KO mice expressed only high levels of fear. We hypothesized that the variability in the wild-type mice may have been due to estrous cycle-mediated changes in the expression of the δ-GABAAR, with low levels of freezing in mice that were in the diestrous phase when dentate gyrus tonic inhibition is high. In the present study we tested this hypothesis by utilizing contextual, delay, and trace fear conditioning protocols in mice that were trained and tested in either the diestrous or estrous phases. Consistent with our hypothesis, we found a significant impairment of hippocampus-dependent learning and memory during diestrus relative to estrus in wild-type mice and this impairment was absent in δ-GABAAR mice. These findings argue that the δ-GABAAR plays an important role in estrous cycle-mediated fluctuations in hippocampus-dependent learning and memory.
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α4-GABAAR KO mice exhibited enhanced trace and contextual fear conditioning, along with enhancement of hippocampus-dependent learning and memory.
“α4-GABAAR knock out (KO) mice exhibited enhanced trace and contextual fear conditioning, along with an enhancement of hippocampus-dependent learning and memory50.”
From Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats (2016) · cites this paper as [50]
The Introduction (p. 3) attributes enhanced trace fear conditioning and hippocampus-dependent learning to female δ-GABAAR knockout mice, not α4-GABAAR knockout mice. The contextual-fear results (p. 6) likewise report enhancement in δ-GABAAR knockout mice. The cited paper therefore identifies a different receptor subunit from the one in the claim. (LLM, conf=0.89)
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- [8]8. Newmark ME, Penry JK (1980) Catamenial epilepsy: a review. Epilepsia 21:281-300
- [9]9. Lundberg PO (1997) Catamenial epilepsy: a review. Cephalalgia 17(Suppl 20):42-45
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An emerging circuit pharmacology of GABAA receptors
Engin, E., Benham, R. S., & Rudolph, U. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.04.003 · Cited by 225 · see citing works
Liu, Z.-H., Ding, J.-J., Yang, Q.-Q., Song, H.-Z., Chen, X.-T., Xu, Y., Xiao, G.-R., & Wang, H.-L. (2016) · Scientific Reports · doi:10.1038/srep32492 · Cited by 53 · see citing works
Lee, V., MacKenzie, G., Hooper, A., & Maguire, J. (2016) · Hippocampus · doi:10.1002/hipo.22604 · Cited by 47 · see citing works
Sabaliauskas, N., Shen, H., Molla, J., Gong, Q. H., Kuver, A., Aoki, C., & Smith, S. S. (2015) · Brain Research · doi:10.1016/j.brainres.2014.12.026 · Cited by 39 · see citing works
Melón, L. C., Nolan, Z. T., Colar, D., Moore, E. M., & Boehm, S. L. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.07.015 · Cited by 18 · see citing works
- Authors
- Cushman, J. D., Moore, M. D., Olsen, R. W., & Fanselow, M. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Cushman, Jesse D.
- Venue
- Neurochemical Research
- Published
- 2014-03-26
- Volume
- 39
- Issue
- 6
- Pages
- 1140-1146
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2084028038
- Cited by
- 33
- References
- 0
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 3
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.escholarship.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (AA07680, NS35985)
- National Institute on Alcohol Abuse and Alcoholism (AA07680)
- National Institute of Mental Health (R01MH062122, MH62122, T32MH019384)
- National Institute of Neurological Disorders and Stroke (NS-35985, P01NS035985)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- estrous cycle, diestrus, hippocampus-dependent learning, memory, fear conditioning, trace fear conditioning, delay fear conditioning, contextual fear, dentate gyrus, tonic inhibition, extrasynaptic inhibition, neurosteroids, female mice
- MeSH terms
- Animals, Fear, Female, Hippocampus, Learning, Memory, Mice, Inbred C57BL, Receptors, GABA-A, Mice, Knockout, Estrous Cycle, Mice
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