Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons.
Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons.
复制标题
脑部对光的情绪价值的感知受到不同下丘脑神经元的调节。
DOI：
10.1038/s41380-022-01567-x
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发表时间：
2022-09
影响因子：
11
通讯作者：
Guo, Su
中科院分区：
文献类型：
--
作者：
Wagle, Mahendra;Zarei, Mahdi;Lovett-Barron, Matthew;Poston, Kristina Tyler;Xu, Jin;Ramey, Vince;Pollard, Katherine S.;Prober, David A.;Schulkin, Jay;Deisseroth, Karl;Guo, Su
显著的感官刺激被大脑感知，大脑以依赖于上下文的方式指导行为的时机和结果。光就是这样一种刺激，它被用于治疗经常与下丘脑-垂体-肾上腺应激轴失调相关的情绪障碍。光的情感价与下丘脑之间的关系，以及它们如何相互作用以产生全脑影响仍然不清楚。采用与哺乳动物类似的下丘脑系统的幼斑马鱼，我们表明在自由游泳的动物，下丘脑促肾上腺皮质激素释放因子（CRFHy）神经元促进黑暗回避，这样的作用是不共享的其他下丘脑肽能神经元。单神经元投射分析揭示了单个CRFHy神经元扩展到多个目标的过程，包括感觉运动和决策区域。体内钙成像揭示了单个CRFHy神经元对光或暗刺激的复杂且不均匀的反应，在光的存在下，CRF神经元活性的总和减少。在交替的光/暗刺激下的全脑钙成像进一步识别不同的和分布的光反应神经元类型。CRFHy神经元消融增加了大脑中光的总体表现，并广泛增强了与探索性大脑状态相关的功能连接。这些发现描绘了全脑光感知，揭示了CRFHy神经元在调节光的感知和情感效价中的先前未知的作用，并表明光疗法可以通过减少CRF神经元活动的总和来缓解情绪障碍。
Salient sensory stimuli are perceived by the brain, which guides both the timing and outcome of behaviors in a context-dependent manner. Light is such a stimulus, which is used in treating mood disorders often associated with a dysregulated hypothalamic-pituitary-adrenal stress axis. Relationships between the emotional valence of light and the hypothalamus, and how they interact to exert brain-wide impacts remain unclear. Employing larval zebrafish with analogous hypothalamic systems to mammals, we show in free-swimming animals that hypothalamic corticotropin releasing factor (CRFHy) neurons promote dark avoidance, and such role is not shared by other hypothalamic peptidergic neurons. Single-neuron projection analyses uncover processes extended by individual CRFHy neurons to multiple targets including sensorimotor and decision-making areas. In vivo calcium imaging uncovers a complex and heterogeneous response of individual CRFHy neurons to the light or dark stimulus, with a reduced overall sum of CRF neuronal activity in the presence of light. Brain-wide calcium imaging under alternating light/dark stimuli further identifies distinct and distributed photic response neuronal types. CRFHy neuronal ablation increases an overall representation of light in the brain and broadly enhances the functional connectivity associated with an exploratory brain state. These findings delineate brain-wide photic perception, uncover a previously unknown role of CRFHy neurons in regulating the perception and emotional valence of light, and suggest that light therapy may alleviate mood disorders through reducing an overall sum of CRF neuronal activity.
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