PT  - JOURNAL ARTICLE
AU  - Deena M. Walker
AU  - Xianxiao Zhou
AU  - Aarthi Ramakrishnan
AU  - Hannah M. Cates
AU  - Ashley M. Cunningham
AU  - Catherine J. Peña
AU  - Rosemary C. Bagot
AU  - Orna Issler
AU  - Yentl Van der Zee
AU  - Andrew P. Lipschultz
AU  - Arthur Godino
AU  - Caleb J. Browne
AU  - Georgia E. Hodes
AU  - Eric M. Parise
AU  - Angélica Torres-Berrio
AU  - Pamela J. Kennedy
AU  - Li Shen
AU  - Bin Zhang
AU  - Eric J. Nestler
TI  - Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward
AID  - 10.1101/2020.02.18.955187
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.18.955187
4099  - http://biorxiv.org/content/early/2020/02/19/2020.02.18.955187.short
4100  - http://biorxiv.org/content/early/2020/02/19/2020.02.18.955187.full
AB  - Adolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid-binding protein, as a key driver of these transcriptional profiles. Manipulation of Crym specifically within adult meA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence.