RT Journal Article
SR Electronic
T1 Sex-Specific Timelines for Adaptations of Prefrontal Parvalbumin Neurons in Response to Stress and Changes in Anxiety- and Depressive-Like Behaviors
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0300-22.2023
DO 10.1523/ENEURO.0300-22.2023
VO 10
IS 3
A1 Emma Woodward
A1 Claudia Rangel-Barajas
A1 Amanda Ringland
A1 Marian L. Logrip
A1 Laurence Coutellier
YR 2023
UL http://www.eneuro.org/content/10/3/ENEURO.0300-22.2023.abstract
AB 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.