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
复制标题
与缰核相关的视觉回路是光疗法抗抑郁作用的基础
DOI：
10.1016/j.neuron.2019.01.037
复制
发表时间：
2019-04-03
期刊：
影响因子：
16.2
通讯作者：
Ren, Chaoran
中科院分区：
文献类型：
--
作者：
Huang, Lu;Xi, Yue;Ren, Chaoran
光线在情感行为的调节中起着关键作用。然而，介导光线对抑郁样行为影响的确切神经回路尚不清楚。在此，我们表明光线通过连接视网膜和外侧缰核（LHb）的双突触回路影响抑郁样行为。具体而言，表达M4型黑视蛋白的视网膜神经节细胞（RGCs）支配丘脑腹外侧膝状体核和膝间小叶（vLGN/IGL）中的γ-氨基丁酸（GABA）能神经元，而这些神经元反过来抑制外侧缰核中的钙/钙调蛋白依赖性蛋白激酶IIα（CaMKIIα）能神经元。特异性激活投射到vLGN/IGL的RGCs、激活投射到LHb的vLGN/IGL神经元，或抑制突触后LHb神经元，都足以减少长期暴露于厌恶性刺激或慢性社会挫败应激所诱发的抑郁样行为。此外，我们证明光疗的抗抑郁作用需要激活视网膜 - vLGN/IGL - LHb通路。这些结果揭示了一个专门调节抑郁样行为的视网膜 - vLGN/IGL - LHb回路，并为光疗抑郁症提供了一种潜在的机制解释。
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 CaMKII alpha 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.