Chemogenetic Activation of Melanopsin Retinal Ganglion Cells Induces Signatures of Arousal and/or Anxiety in Mice.
Chemogenetic Activation of Melanopsin Retinal Ganglion Cells Induces Signatures of Arousal and/or Anxiety in Mice.
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DOI：
10.1016/j.cub.2016.06.057
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发表时间：
2016-09-12
期刊：
影响因子：
9.2
通讯作者：
Lucas, Robert J.
中科院分区：
文献类型：
--
作者：
Milosavljevic, Nina;Cehajic-Kapetanovic, Jasmina;Procyk, Christopher A.;Lucas, Robert J.
功能成像和心理测量评估表明，强光可以改善人类的情绪、注意力和认知表现。间接证据将这些事件与光检测联系在一起，这是通过表达黑素的视网膜神经节细胞(MRGC)来实现的。然而，目前还没有直接的证据表明mRGC可以对任何物种的情绪或行为状态产生如此直接的影响。我们通过使用化学遗传学选择性地激活mRGC来解决这一缺陷，在黑暗环境中模拟强光对这种细胞类型的兴奋效应。这种特定的操作引起了昼夜节律重置和瞳孔收缩(mRGC激活的已知后果)。它还在下丘脑(脑室旁、背内侧和下丘脑外侧)、丘脑(脑室旁和中央正中丘脑)以及边缘系统(杏仁核和伏隔核)的多个核团中诱导c-Fos(神经元激活的标志)。这些区域影响自主神经和神经内分泌活动的许多方面，通常在清醒或觉醒后活跃。相比之下，c-Fos在腹外侧视前区缺失(睡眠时活跃)。在标准的行为测试(开阔场地和高架+迷宫)中，mRGC激活引起的行为通常被解释为焦虑样或警觉性增强的迹象。在野生型、无杆和无视锥的小鼠中，强光可以诱导类似的行为变化，但黑色素基因敲除的小鼠则不能。这些数据表明，mRGC在行为动机中驱动一个光依赖的开关，走向更警觉、更厌恶风险的状态。他们还强调了这一小部分视网膜神经节细胞重新调整大脑区域活动的能力，这些区域定义了生理和行为的广泛方面。化学遗传学被用来在黑暗的动物中重建单一的视觉感觉。单独激活mRGC可重置昼夜节律并收缩瞳孔，激活mRGC可兴奋丘脑、下丘脑和边缘脑区，使行为状态重新调整为警觉和/或焦虑Milosavljevic等人。使用化学遗传学在黑暗中的小鼠身上重建明亮的背景光的感觉。这种选择性的调节重置生物钟；激活丘脑、下丘脑和边缘核，控制行为和生理的不同方面；并诱导提高警觉性和/或焦虑的行为状态。
Functional imaging and psychometric assessments indicate that bright light can enhance mood, attention, and cognitive performance in humans. Indirect evidence links these events to light detection by intrinsically photosensitive melanopsin-expressing retinal ganglion cells (mRGCs). However, there is currently no direct demonstration that mRGCs can have such an immediate effect on mood or behavioral state in any species. We addressed this deficit by using chemogenetics to selectively activate mRGCs, simulating the excitatory effects of bright light on this cell type in dark-housed mice. This specific manipulation evoked circadian phase resetting and pupil constriction (known consequences of mRGC activation). It also induced c-Fos (a marker of neuronal activation) in multiple nuclei in the hypothalamus (paraventricular, dorsomedial, and lateral hypothalamus), thalamus (paraventricular and centromedian thalamus), and limbic system (amygdala and nucleus accumbens). These regions influence numerous aspects of autonomic and neuroendocrine activity and are typically active during periods of wakefulness or arousal. By contrast, c-Fos was absent from the ventrolateral preoptic area (active during sleep). In standard behavioral tests (open field and elevated plus maze), mRGC activation induced behaviors commonly interpreted as anxiety like or as signs of increased alertness. Similar changes in behavior could be induced by bright light in wild-type and rodless and coneless mice, but not melanopsin knockout mice. These data demonstrate that mRGCs drive a light-dependent switch in behavioral motivation toward a more alert, risk-averse state. They also highlight the ability of this small fraction of retinal ganglion cells to realign activity in brain regions defining widespread aspects of physiology and behavior. Chemogenetics is used to recreate a single visual sensation in dark-housed animals mRGC activation alone resets circadian phase and constricts the pupil mRGC activation excites numerous thalamic, hypothalamic, and limbic brain regions mRGC activation realigns behavioral state toward alertness and/or anxiety Milosavljevic et al. use chemogenetics to recreate the sensation of bright background light in mice held in darkness. This selective modulation resets the circadian clock; activates thalamic, hypothalamic, and limbic nuclei controlling diverse aspects of behavior and physiology; and induces a behavioral state of increased alertness and/or anxiety.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
16.2
作者：
Lall, Gurprit S.;Revell, Victoria L.;Momiji, Hiroshi;Al Enezi, Jazi;Altimus, Cara M.;Gueler, Ali D.;Aguilar, Carlos;Cameron, Morven A.;Allender, Susan;Hankins, Mark W.;Lucas, Robert J.
通讯作者：
Lucas, Robert J.
DOI：
10.1073/pnas.1010180107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Vandewalle, G.;Schwartz, S.;Maquet, P.
通讯作者：
Maquet, P.
影响因子：
3.8
作者：
Bouwknecht JA;Spiga F;Staub DR;Hale MW;Shekhar A;Lowry CA
通讯作者：
Lowry CA
DOI：
10.1186/2045-5380-2-5
发表时间：
2012-03-02
期刊：
Biology of mood & anxiety disorders
影响因子：
--
作者：
Kiselycznyk C;Hoffman DA;Holmes A
通讯作者：
Holmes A