PMID- 38480908
OWN - NLM
STAT- Publisher
LR  - 20240314
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Linking)
DP  - 2024 Mar 13
TI  - Elevated dorsal medial prefrontal cortex to lateral habenula pathway activity 
      mediates chronic stress-induced depressive and anxiety-like behaviors.
LID - 10.1038/s41386-024-01840-3 [doi]
AB  - 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 Ca(2+) 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.
CI  - (c) 2024. The Author(s), under exclusive licence to American College of 
      Neuropsychopharmacology.
FAU - Tong, Xiaohan
AU  - Tong X
AUID- ORCID: 0009-0000-9756-941X
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China.
FAU - Wu, Jijin
AU  - Wu J
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China.
FAU - Sun, Ruizhe
AU  - Sun R
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China.
FAU - Li, Han
AU  - Li H
AD  - Guangdong-Hongkong-Macau CNS Regeneration Institute, Key Laboratory of CNS 
      Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human 
      Primate Research, Jinan University, Guangzhou, 510632, China.
FAU - Hong, Yingxi
AU  - Hong Y
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China.
FAU - Liu, Xianwei
AU  - Liu X
AD  - Guangdong-Hongkong-Macau CNS Regeneration Institute, Key Laboratory of CNS 
      Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human 
      Primate Research, Jinan University, Guangzhou, 510632, China.
FAU - Sun, Ying
AU  - Sun Y
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China.
FAU - Chen, Chunxiao
AU  - Chen C
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China.
FAU - Huang, Lu
AU  - Huang L
AD  - Guangdong-Hongkong-Macau CNS Regeneration Institute, Key Laboratory of CNS 
      Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human 
      Primate Research, Jinan University, Guangzhou, 510632, China. huanglu@jnu.edu.cn.
AD  - Emergency Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      510280, China. huanglu@jnu.edu.cn.
FAU - Lin, Song
AU  - Lin S
AUID- ORCID: 0000-0003-0489-9239
AD  - Physiology Department, School of Medicine, Jinan University, Guangzhou, 510632, 
      China. linsong@jnu.edu.cn.
AD  - Guangdong-Hongkong-Macau CNS Regeneration Institute, Key Laboratory of CNS 
      Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human 
      Primate Research, Jinan University, Guangzhou, 510632, China. linsong@jnu.edu.cn.
AD  - Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of 
      Medicine, Jinan University, Guangzhou, 510632, China. linsong@jnu.edu.cn.
AD  - Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Ministry 
      of Education, Jinan University, Guangzhou, 510632, China. linsong@jnu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240313
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
SB  - IM
EDAT- 2024/03/14 06:46
MHDA- 2024/03/14 06:46
CRDT- 2024/03/14 01:09
PHST- 2024/01/10 00:00 [received]
PHST- 2024/02/22 00:00 [accepted]
PHST- 2024/02/14 00:00 [revised]
PHST- 2024/03/14 06:46 [medline]
PHST- 2024/03/14 06:46 [pubmed]
PHST- 2024/03/14 01:09 [entrez]
AID - 10.1038/s41386-024-01840-3 [pii]
AID - 10.1038/s41386-024-01840-3 [doi]
PST - aheadofprint
SO  - Neuropsychopharmacology. 2024 Mar 13. doi: 10.1038/s41386-024-01840-3.