Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats

Yuqi Zhang; Longyu Ma; Xueying Zhang; Lupeng Yue; Jiaxin Wang; Jie Zheng; Shuang Cui; Feng-Yu Liu; Zhiyan Wang; You Wan; Ming Yi

doi:10.1016/j.nbd.2023.106069

Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats

Neurobiol Dis. 2023 May:180:106069. doi: 10.1016/j.nbd.2023.106069. Epub 2023 Mar 8.

Authors

Yuqi Zhang¹, Longyu Ma¹, Xueying Zhang², Lupeng Yue³, Jiaxin Wang¹, Jie Zheng¹, Shuang Cui¹, Feng-Yu Liu¹, Zhiyan Wang⁴, You Wan⁵, Ming Yi⁶

Affiliations

¹ Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China.
² Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
³ CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Science, Beijing 100101, China.
⁴ CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Science, Beijing 100101, China; National Engineering Laboratory for Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing 100084, China. Electronic address: wangzhiyan@psych.ac.cn.
⁵ Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, PR China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: ywan@hsc.pku.edu.cn.
⁶ Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, PR China; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, PR China. Electronic address: mingyi@hsc.pku.edu.cn.

PMID: 36893902
DOI: 10.1016/j.nbd.2023.106069

Abstract

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents. In vivo electrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.

Keywords: Burst firing; Deep brain stimulation; Depression; In vivo recording; Lateral habenula.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Deep Brain Stimulation* / methods
Depression / therapy
Depressive Disorder*
Habenula*
Neurons
Rats