Format

Send to

Choose Destination
Cell Rep. 2018 Nov 27;25(9):2299-2307.e4. doi: 10.1016/j.celrep.2018.11.010.

Early Life Stress Drives Sex-Selective Impairment in Reversal Learning by Affecting Parvalbumin Interneurons in Orbitofrontal Cortex of Mice.

Author information

1
Department of Neuroscience, Brown University, Providence, RI 02912, USA.
2
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
3
Department of Psychiatry and Human Behavior, Brown University, Providence, RI 02912, USA.
4
Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, RI 02912, USA. Electronic address: kevin_bath@brown.edu.

Abstract

Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of females remain unknown. Here, ELS is associated with impaired rule-reversal (RR) learning in females, but not males. Impaired performance was associated with decreased expression and density of interneurons expressing parvalbumin (PV+) in orbitofrontal cortex (OFC), but not other interneuron subtypes. Optogenetic silencing of PV+ interneuron activity in OFC of control mice phenocopied RR learning deficits observed in ELS females. Localization of reversal learning deficits to PV+ interneurons in OFC was confirmed by optogenetic studies in which neurons in medial prefrontal cortex (mPFC) were silenced and associated with select deficits in rule-shift learning. Sex-, cell-, and region-specific effects show altered PV+ interneuron development can be a driver of sex differences in cognitive dysfunction.

KEYWORDS:

attention; behavior; development; early life stress; maternal bedding restriction; mouse; orbitofrontal cortex; parvalbumin; rule-reversal learning; sex differences

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center