Elevated dorsal medial prefrontal cortex to lateral habenula pathway activity mediates chronic stress-induced depressive and anxiety-like behaviors.
Neuropsychopharmacology
; 49(9): 1402-1411, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38480908
ABSTRACT
The medial prefrontal cortex (mPFC) sends projections to numerous brain regions and is believed to play a significant role in depression and anxiety. One of the key downstream targets of the mPFC, the lateral habenula (LHb), is essential for chronic stress (CS)-induced depressive and anxiety-like behaviors. Nevertheless, whether the mPFC-LHb pathway mediates the co-occurrence of depression and anxiety and the underlying mechanism remain incompletely understood. Here, using chemogenetics, we first determined that activation of LHb-projecting mPFC neurons is essential for the development of depressive and anxiety-like behaviors induced by CS. Subsequently, we identify the extent and distribution of LHb-projecting neurons originating from the mPFC subregion. Through circuit-specific in vivo fiber photometry, we found that Ca2+ activity in dorsal mPFC (dmPFC) axon terminals within the LHb was increased during exposure to stressful and anxiety-related stimuli, highlighting the potential role of LHb-projecting dmPFC neurons in conveying stressful and anxiety-related information to the LHb. Finally, we observed that activation of both LHb-projecting dmPFC neurons and their postsynaptic counterparts in the LHb was necessary for CS-induced depressive and anxiety-like behaviors. Overall, this study provides multiple lines of evidence demonstrating that activation of the dmPFC-LHb pathway is a crucial neural circuitry for CS-induced depressive and anxiety-like behaviors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anxiety
/
Stress, Psychological
/
Prefrontal Cortex
/
Habenula
/
Depression
/
Neural Pathways
Limits:
Animals
Language:
En
Journal:
Neuropsychopharmacology
Journal subject:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom