Burst firing in Output‐Defined Parallel Habenula Circuit Underlies the Antidepressant Effects of Bright Light Treatment

Author:

Liu Xianwei1,Li Han1,Ma Ruijia2,Tong Xiaohan2,Wu Jijin2,Huang Xiaodan1,So Kwok‐Fai134,Tao Qian45,Huang Lu1,Lin Song2,Ren Chaoran134ORCID

Affiliation:

1. Department of Neurology and Stroke Center First Affiliated Hospital of Jinan University Key Laboratory of CNS Regeneration (Ministry of Education) Guangdong Key Laboratory of Non‐human Primate Research GHM Institute of CNS Regeneration Jinan University Guangzhou 510632 China

2. Physiology Department Key Laboratory  of  Viral Pathogenesis & Infection Prevention and Control, School of Medicine Jinan University Guangzhou 510632 China

3. Co‐innovation Center of Neuroregeneration Nantong University Nantong 226001 China

4. Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation Sciences Qingdao 266113 China

5. Department of Rehabilitation Medicine First Affiliated Hospital of Jinan University Psychology Department School of Medicine Jinan University Guangzhou 510632 China

Abstract

AbstractResearch highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN‐projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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