17β-Estradiol Enhances NMDA Receptor-Mediated EPSPs and Long-Term Potentiation
Abstract
Gonadal steroid hormones influence CNS functioning through a variety of different mechanisms. To test the hypothesis that estrogen modulates synaptic plasticity in the hippocampus, in vitro hippocampal slices from 2-mo-old Sprague-Dawley male rats were used to determine the effect of 17beta-estradiol on both N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potentials (EPSPs) through intracellular recordings and long-term potentiation (LTP) through extracellular recordings. Intracellular EPSPs and extracellular field EPSPs (fEPSPs) were recorded from CA1 pyramidal cells by stimulating Schaffer collateral fibers. In intracellular experiments, slices were perfused with medium containing bicuculline (5 microM) and low Mg2+ (0.1 mM) to enhance the NMDA receptor-mediated currents and 6, 7-dinitroquinoxaline-2,3-dione (DNQX) (10 microM) to block the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprianate (AMPA) receptor-mediated component. The effects of 17beta-estradiol on NMDA receptor-mediated activity were excitatory; concentrations >10 nM induced seizure activity, and lower concentrations (1 nM) markedly increased the amplitude of NMDA-mediated EPSPs (both the first and second responses increased during paired pulse stimulation by 180 and 197%, respectively). In extracellular experiments, slices perfused with 17beta-estradiol (100 pM) exhibited a pronounced, persisting, and significant enhancement of LTP of both the fEPSP slope (192%) and fEPSP amplitude (177…
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Application of E2 (1-10 nM) induces a baseline increase of the excitatory postsynaptic potential (EPSP) in CA1 neurons.
“In the terms of hippocampal LTP, although application of E2 (1–10 nM) does not directly enhance LTP, it induces a baseline increase of the excitatory postsynaptic potential (EPSP) in CA1 neurons [26, 35].”
From The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation (2017) · cites this paper as [26]
Application of E2 (1-10 nM) does not directly enhance LTP in CA1 neurons.
“In the terms of hippocampal LTP, although application of E2 (1–10 nM) does not directly enhance LTP, it induces a baseline increase of the excitatory postsynaptic potential (EPSP) in CA1 neurons [26, 35].”
From The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation (2017) · cites this paper as [26]
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References 23 · Cited by 519
- Authors
- Foy, M. R., Xu, J., Xie, X., Brinton, R. D., Thompson, R. F., & Berger, T. W.
- Affiliations
- Loyola Marymount University (US)
- University of Southern California (US)
- ORCID
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 1999-02-01
- Volume
- 81
- Issue
- 2
- Pages
- 925-929
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2209257886
- Cited by
- 519
- References
- 23
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 9 · 2023: 11 · 2022: 12 · 2021: 17 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 20 · 2015: 20 · 2014: 16 · 2013: 17 · 2012: 29
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 05142, AG 14751, P01AG014751, P50AG005142)
- National Institute of Mental Health (MH 00343)
- 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
- estradiol, estrogen, NMDA receptor, excitatory postsynaptic potentials, long-term potentiation, synaptic plasticity, hippocampus, CA1 pyramidal neurons, Schaffer collateral stimulation, AMPA receptors, paired pulse, high-frequency stimulation, sex steroids, seizure activity
- MeSH terms
- Animals, Electric Stimulation, Estradiol, Hippocampus, Magnesium, Male, Synaptic Transmission, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Receptors, AMPA, Excitatory Amino Acid Antagonists, Excitatory Postsynaptic Potentials, Rats, In Vitro Techniques
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