Prefrontal Cortical Circuit for Depression- and Anxiety-Related Behaviors Mediated by Cholecystokinin: Role of ΔFosB

• DOI: 10.1523/jneurosci.1787-13.2014
• Publication Date: 2014-03-12T17:44:44Z
• Authors: Vincent Vialou; Rosemary C. Bagot; Michael E. Cahill; Deveroux Ferguson; Alfred J. Robison; David M. Dietz; Barbara Fallon; Michelle Mazei-Ro...; Stacy M. Ku; Eileen Harrigan; Catherine A. Wins...; Tej Joshi; Jian Feng; Olivier Berton; Eric J. Nestler
• Keywords: Social defeat; Basolateral amygdala; FOSB; Anxiogenic; Neurochemical

Decreased medial prefrontal cortex (mPFC) neuronal activity is associated with social defeat-induced depression- and anxiety-like behaviors in mice. However, the molecular mechanisms underlying decreased mPFC its prodepressant role remain unknown. We show here that induction of transcription factor ΔFosB mPFC, specifically prelimbic (PrL) area, mediates susceptibility to stress. PrL occurred selectively susceptible mice after chronic defeat stress, overexpression this region, but not nearby infralimbic (IL) enhanced stress susceptibility. produced these effects partly through cholecystokinin (CCK)-B receptor: CCKB blockade induces a resilient phenotype, whereas CCK administration into mimics anxiogenic- depressant-like previously found optogenetic stimulation neurons reverses several behavioral abnormalities seen Therefore, we hypothesized cortical projections would rescue pathological mPFC. After infusion optogenetically stimulated basolateral amygdala or nucleus accumbens, two subcortical structures involved mood regulation. Stimulation corticoamygdala blocked anxiogenic effect CCK, although no was observed on other symptoms defeat. Conversely, corticoaccumbens reversed CCK-induced avoidance sucrose preference deficits anxiogenic-like effects. Together, results indicate stress-induced are mediated by adaptations involving distinct targets.