Journal article
Estradiol receptors inhibit long-term potentiation in the dorsomedial striatum
eNeuro, Vol.10(8), ENEURO.0071-23.2023
07/24/2023
DOI: 10.1523/ENEURO.0071-23.2023
Abstract
Estradiol, a female sex hormone and the predominant form of estrogen, has diverse effects throughout the brain including in learning and memory. Estradiol modulates several types of learning that depend on the dorsomedial striatum (DMS), a subregion of the basal ganglia involved in goal-directed learning, cued action-selection, and motor skills. A cellular basis of learning is synaptic plasticity, and the presence of extranuclear estradiol receptors ERα, ERβ, and G-protein-coupled estrogen receptor (GPER) throughout the DMS suggests that estradiol may influence rapid cellular actions including those involved in plasticity. To test whether estradiol affects synaptic plasticity in the DMS, corticostriatal long-term potentiation (LTP) was induced using theta-burst stimulation (TBS) in ex vivo brain slices from intact male and female C57BL/6 mice. Extracellular field recordings showed that female mice in the diestrous stage of the estrous cycle exhibited LTP similar to male mice, while female mice in estrus did not exhibit LTP. Furthermore, antagonists of ERα or GPER rescued LTP in estrous females and agonists of ERα or GPER reduced LTP in diestrous females. In males, activating ERα but not GPER reduced LTP. These results uncover an inhibitory action of estradiol receptors on cellular learning in the DMS and suggest a cellular mechanism underlying the impairment in certain types of DMS-based learning observed in the presence of high estradiol. Because of the dorsal striatum’s role in substance use disorders, these findings may provide a mechanism underlying an estradiol-mediated progression from goal-directed to habitual drug use.
Details
- Title: Subtitle
- Estradiol receptors inhibit long-term potentiation in the dorsomedial striatum
- Creators
- V J LewitusK T Blackwell
- Resource Type
- Journal article
- Publication Details
- eNeuro, Vol.10(8), ENEURO.0071-23.2023
- DOI
- 10.1523/ENEURO.0071-23.2023
- eISSN
- 2373-2822
- Grant note
- DOI: 10.13039/100000027, name: HHS | NIH | National Institute on Alcohol Abuse and Alcoholism, award: R01 016022; DOI: 10.13039/100000026, name: HHS | NIH | National Institute on Drug Abuse, award: R01 038890, R01 056113; DOI: 10.13039/100009979, name: GMU | College of Science, George Mason University, award: Presidential Scholarship, Dissertation Completion Grant
- Language
- English
- Date published
- 07/24/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
- Record Identifier
- 9984446691602771
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