RT Journal Article
T1 Activational and Organizational Effects of Sex Hormones on Hippocampal Inhibitory Neurons
A1 Hernández-Vivanco, Alicia
A1 Vega-Ruiz, Rut de la
A1 Montes-Mellado, Alberto
A1 Azcoitia Elías, Íñigo
A1 Méndez, Pablo
AB 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
PB Society for Neuroscience
SN 0270-6474
YR 2025
FD 2025-03-17
LK https://hdl.handle.net/20.500.14352/120355
UL https://hdl.handle.net/20.500.14352/120355
LA eng
NO Mendez, P. (2025). Activational and organizational effects of sex hormones on hippocampal inhibitory neurons. The Journal of Neuroscience, 45(18) https://doi.org/10.1523/JNEUROSCI.1764-24.2025
NO Funding: This work was supported by a Whitehall Foundation grant, NARSAD Young Investigator Fellowship, Outstanding Early Investigator Award, Charles H. Hood Foundation Award, and the NINDS of the NIH under award number 1R01NS104917 to G.D. and a Gruber Science Fellowship to U.F. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.Author contributions: G.D. conceived and designed the study. U.F. and G.D. collected and analyzed the data. G.D. and U.F. wrote the manuscript.Competing interests: The authors declare no conflicts of interest.Data and materials availability: All data are available in the manuscript or the supplementary material. The reported data are archived on file servers at Yale Medical School
NO Whitehall Foundation
NO Brain and Behavior Research Foundation (NARSAD)
NO Charles H. Hood Foundation
NO National Institute of Neurological Disorders and Stroke (NINDS, NIH)
NO Gruber Foundation
DS Docta Complutense
RD 6 jun 2025