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A Visual Circuit Related to Habenula Underlies the Antidepres
AAV-Cre was used for monosynaptic anterograde transport. A trans-synaptic tracing method based on a modified rabies virus was used to determine whether LHb-projecting vLGN/IGL neurons receive direct innervation from RGCs. (All viruses were packaged by BrainVTA)
The viruses used in this article from BrainVTA are in the table below
Control  PT-0012 AAV2/9-Ef1a-DIO-eYFP
CRE Recombinase  PT-0136 AAV2/1-hSyn-Cre
Tracing Helper  PT-0022 AAV2/9-hSyn-EGFP-2a-TVA-2a-RVG-WPREs-pA
RV  R01002 RV SAD-DG-DsRed (EnvA)
Pub Date: 2019-02-19, DOI: 10.1016/j.neuron.2019.01.037, Email: [email protected]
Lu Huang, Yue Xi, Yanfang Peng, Yan Yang, Xiaodan Huang, Yunwei Fu, Qian Tao, Jia Xiao, Tifei Yuan, Kai An, Huan Zhao, Mingliang Pu, Fuqiang Xu, Tian Xue, Minmin Luo, Kwok-Fai So and Chaoran Ren
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 intergen-iculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIa neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHb-projecting vLGN/IGL neurons, or inhibition of post-synaptic 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.

Figure 1. M4-type mRGCs Directly Innervate the vLGN/IGL-LHb Pathway
By combining conventional neurotracer and transneuronal virus tracing techniques, the authors identified a visual circuit related to the LHb that regulates depressive-like behaviors. They demonstrate that activation of the disynaptic retina-vLGN/IGL-LHb pathway underlies the antidepressive effects of light therapy.
 
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