Amygdala circuitry mediating reversible and bidirectional control of anxiety.
Amygdala circuitry mediating reversible and bidirectional control of anxiety.
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DOI：
10.1038/nature09820
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发表时间：
2011-03-17
期刊：
影响因子：
64.8
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
--
作者：
Tye, Kay M.;Prakash, Rohit;Kim, Sung-Yon;Fenno, Lief E.;Grosenick, Logan;Zarabi, Hosniya;Thompson, Kimberly R.;Gradinaru, Viviana;Ramakrishnan, Charu;Deisseroth, Karl
焦虑是一种在没有直接威胁的情况下持续的高度恐惧状态，在疾病状态下会变得严重衰弱。焦虑症是最常见的精神疾病（28%的终生患病率），并导致严重抑郁症和药物滥用的病因。虽然有人提出杏仁核（大脑中一个对情绪处理很重要的区域）在焦虑中起作用，但控制焦虑的神经机制仍不清楚。在这里，我们探索神经回路的焦虑相关的行为，通过使用光遗传学与双光子显微镜，在自由移动的小鼠焦虑测定，和电生理学。利用光遗传学不仅控制细胞类型而且控制细胞之间的特定连接的能力，我们观察到杏仁核中央核中的基底外侧杏仁核（BLA）末端的时间精确的光遗传学刺激（CeA-通过用密码子优化的通道视紫红质病毒转导BLA，然后在下游CeA-中限制照明来实现）产生急性、可逆的抗焦虑作用。相反，用第三代盐视紫红质（eNpHR3.0）选择性光遗传学抑制相同的投射增加了焦虑相关的行为。重要的是，在BLA胞体的直接光遗传学控制下没有观察到这些效应，这可能是由于拮抗性下游结构的募集。总之，这些结果暗示特定的BLA-CeA预测作为哺乳动物大脑中急性焦虑控制的关键电路元件，并证明了光遗传学靶向定义的预测的重要性，而不仅仅是靶向细胞类型，在神经精神疾病相关电路功能的研究中。
Anxiety, a sustained state of heightened apprehension in the absence of immediate threat, becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence), and contribute to the etiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, neural mechanisms that control anxiety remain unclear. Here we explore neural circuits underlying anxiety-related behaviors by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA-achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in downstream CeA - exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviors. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA-CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.
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在大鼠和人类中持续的恐惧：恐惧与焦虑中的杏仁核的作用。
DOI：
10.1038/npp.2009.109
发表时间：
2010-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
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影响因子：
2.9
作者：
Koob GF
通讯作者：
Koob GF
影响因子：
64.8
作者：
Ciocchi, Stephane;Herry, Cyril;Luethi, Andreas
通讯作者：
Luethi, Andreas
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
2.5
作者：
CARLSEN, J
通讯作者：
CARLSEN, J