Back to Search
Start Over
Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: role of ΔFosB.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Mar 12; Vol. 34 (11), pp. 3878-87. - Publication Year :
- 2014
-
Abstract
- 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 the decreased mPFC activity and its prodepressant role remain unknown. We show here that induction of the transcription factor ΔFosB in mPFC, specifically in the prelimbic (PrL) area, mediates susceptibility to stress. ΔFosB induction in PrL occurred selectively in susceptible mice after chronic social defeat stress, and overexpression of ΔFosB in this region, but not in the nearby infralimbic (IL) area, enhanced stress susceptibility. ΔFosB produced these effects partly through induction of the cholecystokinin (CCK)-B receptor: CCKB blockade in mPFC induces a resilient phenotype, whereas CCK administration into mPFC mimics the anxiogenic- and depressant-like effects of social stress. We previously found that optogenetic stimulation of mPFC neurons in susceptible mice reverses several behavioral abnormalities seen after chronic social defeat stress. Therefore, we hypothesized that optogenetic stimulation of cortical projections would rescue the pathological effects of CCK in mPFC. After CCK infusion in mPFC, we optogenetically stimulated mPFC projections to basolateral amygdala or nucleus accumbens, two subcortical structures involved in mood regulation. Stimulation of corticoamygdala projections blocked the anxiogenic effect of CCK, although no effect was observed on other symptoms of social defeat. Conversely, stimulation of corticoaccumbens projections reversed CCK-induced social avoidance and sucrose preference deficits but not anxiogenic-like effects. Together, these results indicate that social stress-induced behavioral deficits are mediated partly by molecular adaptations in mPFC involving ΔFosB and CCK through cortical projections to distinct subcortical targets.
- Subjects :
- Animals
Anti-Anxiety Agents pharmacology
Anxiety Disorders pathology
Brain Mapping
Chronic Disease
Depressive Disorder pathology
Indoles pharmacology
Limbic System cytology
Limbic System drug effects
Limbic System physiology
Male
Meglumine analogs & derivatives
Meglumine pharmacology
Mice
Mice, Inbred C57BL
Neural Pathways physiology
Prefrontal Cortex cytology
Prefrontal Cortex drug effects
Proto-Oncogene Proteins c-fos genetics
Receptor, Cholecystokinin B antagonists & inhibitors
Receptor, Cholecystokinin B genetics
Social Dominance
Stress, Psychological pathology
Stress, Psychological physiopathology
Anxiety Disorders physiopathology
Cholecystokinin physiology
Depressive Disorder physiopathology
Prefrontal Cortex physiology
Proto-Oncogene Proteins c-fos physiology
Receptor, Cholecystokinin B physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 34
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 24623766
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.1787-13.2014