Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons

Peripheral and brain-produced sex hormones exert sex-specific regulation of hippocampal cognitive function. Estrogens produced by neuronal aromatase regulate inhibitory neurons (INs) and hippocampal-dependent memory in adult female mice, but not in males. How and when this sex effect is established...

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Autores: Hernández-Vivanco, Alicia, de la Vega-Ruiz, R., Montes-Mellado, Alberto, Azcoitia, Íñigo, Méndez, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/406874
Acceso en línea:http://hdl.handle.net/10261/406874
Access Level:acceso abierto
Palabra clave:estrogen, hippocampus, inhibitory neuron, sex differences, testosterone
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spelling Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory NeuronsHernández-Vivanco, Aliciade la Vega-Ruiz, R.Montes-Mellado, AlbertoAzcoitia, ÍñigoMéndez, Pabloestrogen, hippocampus, inhibitory neuron, sex differences, testosteronePeripheral and brain-produced sex hormones exert sex-specific regulation of hippocampal cognitive function. Estrogens produced by neuronal aromatase regulate inhibitory neurons (INs) and hippocampal-dependent memory in adult female mice, but not in males. How and when this sex effect is established and how peripheral and brain sources of estrogens interact in the control of hippocampal INs is currently unknown. Using ex vivo electrophysiology, fiber photometry, molecular analysis, estrous cycle monitoring, and neonatal hormonal manipulations, we unveil estrous cycle-dependent and estrous cycle-independent features of CA1 parvalbumin (PV) INs and hippocampal inhibition in adult female mice. Before puberty, aromatase is expressed in PV INs and regulates synaptic inhibition in female but not in male mice. Neonatal testosterone administration altered prepubertal female mouse hippocampus-dependent memory, PV IN function and estrogenic regulation of adult female synaptic inhibition and PV IN perineuronal nets. Our results suggest that sex differences in brain-derived estrogen regulation of CA1 inhibition are established by organizational effects of neonatal gonadal hormones and highlight the role of INs as mediators of the sexual differentiation of the hippocampus.This work was supported by grants PID2020-112428GB-I00 and PID2023-147398NB-I00 by MICIU/AEI/ 10.13039/501100011033 to P.M. A.M-M is supported by a JAEIntro scholarship funded by CSIC. R.D.L.V-R. is supported by the Ph.D. fellowship PRE2021-099806 funded by MICIU/AEI/10.13039/501100011033 by “ESF Investing in your future.” We thank Beatriz Rico (King’s College, London, UK) for providing the plasmids used to generate the aromatase gene knockdown.Society for NeuroscienceMinisterio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/406874reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-147398NB-I00http://dx.doi.org/10.1523/jneurosci.1764-24.2025Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4068742026-05-22T06:33:51Z
dc.title.none.fl_str_mv Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
title Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
spellingShingle Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
Hernández-Vivanco, Alicia
estrogen, hippocampus, inhibitory neuron, sex differences, testosterone
title_short Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
title_full Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
title_fullStr Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
title_full_unstemmed Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
title_sort Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
dc.creator.none.fl_str_mv Hernández-Vivanco, Alicia
de la Vega-Ruiz, R.
Montes-Mellado, Alberto
Azcoitia, Íñigo
Méndez, Pablo
author Hernández-Vivanco, Alicia
author_facet Hernández-Vivanco, Alicia
de la Vega-Ruiz, R.
Montes-Mellado, Alberto
Azcoitia, Íñigo
Méndez, Pablo
author_role author
author2 de la Vega-Ruiz, R.
Montes-Mellado, Alberto
Azcoitia, Íñigo
Méndez, Pablo
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv estrogen, hippocampus, inhibitory neuron, sex differences, testosterone
topic estrogen, hippocampus, inhibitory neuron, sex differences, testosterone
description Peripheral and brain-produced sex hormones exert sex-specific regulation of hippocampal cognitive function. Estrogens produced by neuronal aromatase regulate inhibitory neurons (INs) and hippocampal-dependent memory in adult female mice, but not in males. How and when this sex effect is established and how peripheral and brain sources of estrogens interact in the control of hippocampal INs is currently unknown. Using ex vivo electrophysiology, fiber photometry, molecular analysis, estrous cycle monitoring, and neonatal hormonal manipulations, we unveil estrous cycle-dependent and estrous cycle-independent features of CA1 parvalbumin (PV) INs and hippocampal inhibition in adult female mice. Before puberty, aromatase is expressed in PV INs and regulates synaptic inhibition in female but not in male mice. Neonatal testosterone administration altered prepubertal female mouse hippocampus-dependent memory, PV IN function and estrogenic regulation of adult female synaptic inhibition and PV IN perineuronal nets. Our results suggest that sex differences in brain-derived estrogen regulation of CA1 inhibition are established by organizational effects of neonatal gonadal hormones and highlight the role of INs as mediators of the sexual differentiation of the hippocampus.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/406874
url http://hdl.handle.net/10261/406874
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-147398NB-I00
http://dx.doi.org/10.1523/jneurosci.1764-24.2025
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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