2. Academic Validation
  3. A Visual Circuit Related to Habenula Underlies the Antidepressive Effects of Light Therapy

A Visual Circuit Related to Habenula Underlies the Antidepressive Effects of Light Therapy

  • Neuron. 2019 Apr 3;102(1):128-142.e8. doi: 10.1016/j.neuron.2019.01.037.
Lu Huang 1,  Yue Xi 2,  Yanfang Peng 2,  Yan Yang 2,  Xiaodan Huang 2,  Yunwei Fu 2,  Qian Tao 3,  Jia Xiao 4,  Tifei Yuan 5,  Kai An 6,  Huan Zhao 6,  Mingliang Pu 7,  Fuqiang Xu 8,  Tian Xue 6,  Minmin Luo 9,  Kwok-Fai So 10,  Chaoran Ren 11
Affiliations

Affiliations

  • 1 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China; Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
  • 2 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China.
  • 3 Psychology Department, School of Medicine, Jinan University, Guangzhou 510632, China.
  • 4 Clinical Medicine Research Institute, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
  • 5 Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
  • 6 Hefei National Laboratory for Physical Sciences at the Microscale, Neurodegenerative Disorder Research Center, Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
  • 7 Department of Anatomy, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 8 State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences, Wuhan 430071, China.
  • 9 National Institute of Biological Sciences, Zhongguancun Life Science Park 7 Science Park Road, Beijing 102206, China.
  • 10 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510530, China; Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
  • 11 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510530, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: tchaoran@jnu.edu.cn.
PMID: 30795900 DOI: 10.1016/j.neuron.2019.01.037
Abstract

Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressive-like behaviors are not well understood. Here, we show that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenula (LHb). Specifically, M4-type melanopsin-expressing retinal ganglion cells (RGCs) innervate GABA neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIα neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHb-projecting vLGN/IGL neurons, or inhibition of postsynaptic LHb neurons is sufficient to decrease the depressive-like behaviors evoked by long-term exposure to aversive stimuli or chronic social defeat stress. Furthermore, we demonstrate that the antidepressive effects of light therapy require activation of the retina-vLGN/IGL-LHb pathway. These results reveal a dedicated retina-vLGN/IGL-LHb circuit that regulates depressive-like behaviors and provide a potential mechanistic explanation for light treatment of depression.

Keywords

depression; lateral habenula; light therapy; retina.

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