Diverging neural pathways assemble a behavioural state from separable features in anxiety.
Diverging neural pathways assemble a behavioural state from separable features in anxiety.
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DOI：
10.1038/nature12018
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发表时间：
2013-04-11
期刊：
影响因子：
64.8
通讯作者：
Deisseroth K
中科院分区：
文献类型：
--
作者：
Kim SY;Adhikari A;Lee SY;Marshel JH;Kim CK;Mallory CS;Lo M;Pak S;Mattis J;Lim BK;Malenka RC;Warden MR;Neve R;Tye KM;Deisseroth K
哺乳动物的行为状态，例如焦虑状态，具有多种由不同神经系统输出协调调节的特征，从行为选择模式到生理变化（在焦虑中，分别以风险规避和呼吸频率改变为例）。在这里，我们研究了小鼠单个协调大脑区域产生的明确神经投射是否以及如何介导焦虑的不同特征。综合行为分析、体内和体外电生理学、呼吸生理学和光遗传学，我们发现了终纹床核（BNST）在协调调节不同焦虑特征中的令人惊讶的新作用。首先，意外地发现两个 BNST 亚区对焦虑状态产生相反的影响：椭圆形 BNST 活动促进了几种独立的焦虑状态特征，而前背侧 BNST 相关活动对相同特征产生抗焦虑影响。值得注意的是，我们发现三个不同的前背侧 BNST 传出投射——下丘脑外侧、臂旁核和腹侧被盖区——各自实现了抗焦虑的独立特征：分别降低风险规避、降低呼吸频率和增加正价。此外，在自由活动的小鼠中，选择性抑制相应的电路元件显示出与兴奋相反的行为效应，并且自由行为期间的体内记录显示了前背 BNST 神经元的天然尖峰模式，可以区分安全环境和致焦虑环境。这些结果表明，不同的 BNST 亚区在调节焦虑方面发挥相反的作用，为不同的前背 BNST 投射建立可分离的抗焦虑作用，并说明了焦虑状态组装特征选择的回路机制。
Behavioural states in mammals, such as the anxious state, are characterized by several features that are coordinately regulated by diverse nervous system outputs, ranging from behavioural choice patterns to changes in physiology (in anxiety, exemplified respectively by risk-avoidance and respiratory rate alterations). Here we investigate if and how defined neural projections arising from a single coordinating brain region in mice could mediate diverse features of anxiety. Integrating behavioural assays, in vivo and in vitro electrophysiology, respiratory physiology and optogenetics, we identify a surprising new role for the bed nucleus of the stria terminalis (BNST) in the coordinated modulation of diverse anxiety features. First, two BNST subregions were unexpectedly found to exert opposite effects on the anxious state: oval BNST activity promoted several independent anxious state features, whereas anterodorsal BNST-associated activity exerted anxiolytic influence for the same features. Notably, we found that three distinct anterodorsal BNST efferent projections—to the lateral hypothalamus, parabrachial nucleus and ventral tegmental area—each implemented an independent feature of anxiolysis: reduced risk-avoidance, reduced respiratory rate, and increased positive valence, respectively. Furthermore, selective inhibition of corresponding circuit elements in freely moving mice showed opposing behavioural effects compared with excitation, and in vivo recordings during free behaviour showed native spiking patterns in anterodorsal BNST neurons that differentiated safe and anxiogenic environments. These results demonstrate that distinct BNST subregions exert opposite effects in modulating anxiety, establish separable anxiolytic roles for different anterodorsal BNST projections, and illustrate circuit mechanisms underlying selection of features for the assembly of the anxious state.
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影响因子：
2.5
作者：
DUNN, JD;WILLIAMS, TJ
通讯作者：
WILLIAMS, TJ
影响因子：
10.6
作者：
Singewald, N;Salchner, P;Sharp, T
通讯作者：
Sharp, T
影响因子：
--
作者：
Kessler, RC;Berglund, P;Walters, EE
通讯作者：
Walters, EE
影响因子：
22.4
作者：
MARTIN, B
通讯作者：
MARTIN, B
在持续类似焦虑的恐惧样反应中，质子末端和CRF的床核的选择性参与。
DOI：
10.1016/j.pnpbp.2009.06.022
发表时间：
2009-11-13
影响因子：
5.6
作者：
Walker, D. L.;Miles, L. A.;Davis, M.
通讯作者：
Davis, M.