Estrogen regulates functional inhibition of hippocampal CA1 pyramidal cells in the adult female rat
Open accessAbstract
Previous studies have focused considerable attention on the effects of estrogen on excitatory synaptic input to hippocampal CA1 pyramidal cells. Estrogen increases the density of dendritic spines and synapses on CA1 pyramidal cells and increases the sensitivity of these cells to excitatory synaptic input. Little is known, however, about the effects of estrogen on inhibitory synaptic input to CA1 pyramidal cells. We have used immunohistochemistry for glutamic acid decarboxylase and whole-cell voltage-clamp recording of IPSCs and EPSCs at multiple time points after estrogen treatment to (1) investigate estrogen regulation of synaptic inhibition in CA1 and (2) evaluate how estrogen affects the interaction between inhibitory and excitatory input to CA1 pyramidal cells. We find that estrogen transiently suppresses GABA(A)-mediated inhibition of CA1 pyramidal cells at a time point before changes in excitatory input to these cells occur. This finding is consistent with the suggestion that transient disinhibition of CA1 pyramidal cells is involved in estrogen-induced dendritic spine formation. We have also found that at a later time after estrogen, inhibition of CA1 pyramidal cells recovers in parallel with enhancement of NMDA-mediated excitatory input. The concurrent enhancement of GABA(A) and NMDA-mediated input to CA1 pyramidal cells restores a balance of excitatory and inhibitory input to these cells and increases the potential dynamic range of CA1 pyramidal cell responses to synaptic input.
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Estrogen is synthesized in the hippocampus and increases intrinsic neuronal excitability and long-term potentiation in the hippocampus while decreasing inhibitory transmission.
“Synthesized in the hippocampus, estrogen is shown to increase intrinsic neuronal excitability and long-term potentiation in the hippocampus (Christian et al., 2020) while decreasing inhibitory transmission (Rudick and Woolley, 2001).”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Rudick and Woolley, 2001
Rudick and Woolley support the part attached to their citation: the Abstract reports that estrogen transiently suppresses GABAₐ-mediated inhibition of CA1 pyramidal cells in adult female rats. The claim omits that this decrease is temporary; the Abstract and the section “Dynamic balance of excitatory and inhibitory synaptic input” report that inhibition later recovers and is enhanced relative to controls. (LLM, conf=0.88)
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“, 1998; Rudick and Woolley, 2001) and increase NMDAR expression and function (Weiland, 1992; Warren et al., 1995; Gazzaley et al., 1996; Cordoba Montoya and Carrer, 1997; Woolley et al., 1997; Good et al., 1999; Cyr et al., 2000, 2001; Bi et al., 2001; Rudick and Woolley, 2001), ultimately increasing the spine density…”
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Singh, T., Bridgeman, E., Baker, A. J., Noblet, H. A., Yang, K. Y., Kang, S., Lim, K. H., Lee, S. S., Amundsen, N. M., Lee, Y., et al. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107246 · Cited by 1 · see citing works
- Authors
- Rudick, C. N., & Woolley, C. S.
- Affiliations
- Northwestern University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-09-01
- Volume
- 21
- Issue
- 17
- Pages
- 6532-6543
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763095
- OpenAlex
- W2103715310
- Cited by
- 228
- References
- 2
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 11 · 2012: 13
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alfred P. Sloan Foundation
- National Institutes of Health (NS37324)
- National Institute of General Medical Sciences (GM08061, T32GM008061)
- National Institute of Neurological Disorders and Stroke (NS37324, R29NS037324, R01NS037324)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- estrogen, CA1 pyramidal neurons, synaptic inhibition, GABAA receptor, NMDA receptor, inhibitory postsynaptic currents, excitatory postsynaptic currents, dendritic spine formation, excitation-inhibition balance, synaptic plasticity, female rats
- MeSH terms
- Animals, Cell Count, Electric Stimulation, Estradiol, Estrogens, Female, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Hippocampus, Immunohistochemistry, Isoenzymes, Neural Inhibition, Ovariectomy, Receptors, GABA-A, Synapses, Tetrodotoxin, Time Factors, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Pyramidal Cells, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Excitatory Postsynaptic Potentials, Rats
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