| First Author | Goodwill HL | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 9 | Pages | 2299-2307.e4 |
| PubMed ID | 30485800 | Mgi Jnum | J:270841 |
| Mgi Id | MGI:6278326 | Doi | 10.1016/j.celrep.2018.11.010 |
| Citation | Goodwill HL, et al. (2018) Early Life Stress Drives Sex-Selective Impairment in Reversal Learning by Affecting Parvalbumin Interneurons in Orbitofrontal Cortex of Mice. Cell Rep 25(9):2299-2307.e4 |
| abstractText | 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. |
