Weil Tenley, Daly K M, Yarur Castillo Hector, Thomsen Michael B, Wang Huikun, Mercau Maria E, Hattar Samer, Tejeda Hugo, Fernandez Diego C
Section on Light and Circadian Rhythms (SLCR), National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Sci Adv. 2022 Jun 10;8(23):eabn3567. doi: 10.1126/sciadv.abn3567.
Exposure to irregular lighting schedules leads to deficits in affective behaviors. The retino-recipient perihabenular nucleus (PHb) of the dorsal thalamus has been shown to mediate these effects in mice. However, the mechanisms of how light information is processed within the PHb remains unknown. Here, we show that the PHb contains a distinct cluster of GABAergic neurons that receive direct retinal input. These neurons are part of a larger inhibitory network composed of the thalamic reticular nucleus and zona incerta, known to modulate thalamocortical communication. In addition, PHb neurons locally modulate excitatory-relay neurons, which project to limbic centers. Chronic exposure to irregular light-dark cycles alters photo-responsiveness and synaptic output of PHb neurons, disrupting daily oscillations of genes associated with inhibitory and excitatory PHb signaling. Consequently, selective and chronic PHb manipulation results in mood alterations that mimic those caused by irregular light exposure. Together, light-mediated disruption of PHb inhibitory networks underlies mood deficits.
暴露于不规律的光照时间表会导致情感行为缺陷。已表明，背侧丘脑的视网膜接受区缰周核（PHb）在小鼠中介导这些效应。然而，光信息在PHb内如何处理的机制仍不清楚。在这里，我们表明PHb包含一组独特的接受视网膜直接输入的GABA能神经元。这些神经元是由丘脑网状核和未定带组成的更大抑制性网络的一部分，已知该网络可调节丘脑皮质通信。此外，PHb神经元局部调节投射到边缘中枢的兴奋性中继神经元。长期暴露于不规律的明暗周期会改变PHb神经元的光反应性和突触输出，破坏与PHb抑制性和兴奋性信号相关基因的每日振荡。因此，选择性和慢性的PHb操纵会导致情绪改变，类似于不规律光照暴露所引起的情绪改变。总之，光介导的PHb抑制性网络破坏是情绪缺陷的基础。
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