Potentiation of the Lateral Habenula-ventral Tegmental Area Pathway Underlines the Susceptibility to Depression in Mice with Chronic Pain

Overview

Journal Sci China Life Sci

Specialties Biology
Science

Date 2023 Oct 20

PMID 37864083

Authors

Chun-Kui Zhang

Pan Wang

Yuan-Yuan Ji

Jian-Shuai Zhao

Jun-Xiang Gu

Xian-Xia Yan

Hong-Wei Fan

Ming-Ming Zhang

Yu Qiao

Xiao-Die Liu

Bao-Juan Li

Ming-Hui Wang

Hai-Long Dong

Hao-Hong Li

Peng-Cheng Huang

Yun-Qing Li

Wu-Gang Hou

Jin-Lian Li

Tao Chen

Affiliations

Soon will be listed here.

Abstract

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHb-VTA-VTA circuit. Furthermore, the LHb-VTA excitatory inputs were dampened via GABA receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHb-to-VTA inhibition in depressive behavioral regulation.

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