Sex-Specific Timelines for Adaptations of Prefrontal Parvalbumin Neurons in Response to Stress and Changes in Anxiety- and Depressive-Like Behaviors.

Autor:	Woodward E; Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210., Rangel-Barajas C; Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Ringland A; Department of Psychology, The Ohio State University, Columbus, Ohio 43210., Logrip ML; Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202.; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202., Coutellier L; Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210 Coutellier.8@osu.edu.; Department of Psychology, The Ohio State University, Columbus, Ohio 43210.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2023 Mar 02; Vol. 10 (3). Date of Electronic Publication: 2023 Mar 02 (Print Publication: 2023).
DOI:	10.1523/ENEURO.0300-22.2023
Abstrakt:	Women are twice as likely as men to experience emotional dysregulation after stress, resulting in substantially higher psychopathology for equivalent lifetime stress exposure, yet the mechanisms underlying this vulnerability remain unknown. Studies suggest changes in medial prefrontal cortex (mPFC) activity as a potential contributor. Whether maladaptive changes in inhibitory interneurons participate in this process, and whether adaptations in response to stress differ between men and women, producing sex-specific changes in emotional behaviors and mPFC activity, remained undetermined. This study examined whether unpredictable chronic mild stress (UCMS) in mice differentially alters behavior and mPFC parvalbumin (PV) interneuron activity by sex, and whether the activity of these neurons drives sex-specific behavioral changes. Four weeks of UCMS increased anxiety-like and depressive-like behaviors associated with FosB activation in mPFC PV neurons, particularly in females. After 8 weeks of UCMS, both sexes displayed these behavioral and neural changes. Chemogenetic activation of PV neurons in UCMS-exposed and nonstressed males induced significant changes in anxiety-like behaviors. Importantly, patch-clamp electrophysiology demonstrated altered excitability and basic neural properties on the same timeline as the emergence of behavioral effects: changes in females after 4 weeks and in males after 8 weeks of UCMS. These findings show, for the first time, that sex-specific changes in the excitability of prefrontal PV neurons parallel the emergence of anxiety-like behavior, revealing a potential novel mechanism underlying the enhanced vulnerability of females to stress-induced psychopathology and supporting further investigation of this neuronal population to identify new therapeutic targets for stress disorders. Competing Interests: The authors declare no competing financial interests. (Copyright © 2023 Woodward et al.)
Databáze:	MEDLINE
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