Parallel circuits from the bed nuclei of stria terminalis to the lateral hypothalamus drive opposing emotional states.

Parallel circuits from the bed nuclei of stria terminalis to the lateral hypothalamus drive opposing emotional states.
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DOI:
10.1038/s41593-018-0198-x
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发表时间:
2018-08
影响因子:
25
通讯作者:
de Lecea L
de Lecea L
中科院分区:
医学1区
文献类型:
--
作者:
Giardino WJ;Eban-Rothschild A;Christoffel DJ;Li SB;Malenka RC;de Lecea L

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外侧下丘脑(LH)神经元含有神经肽下丘脑泌素(Hcrt;食欲素)调节唤醒的情感成分,但其相关的突触输入仍然不清楚。在这里,我们确定了LH神经元的输入,起源于终纹床核(BNST;扩展杏仁核的异质区域)的神经元群体。我们的特点是两个非重叠LH-投射GABA能BNST亚群,表达不同的神经肽(促肾上腺皮质激素释放因子; Crf,胆囊收缩素; Cck)。为了在功能上询问BNST→LH回路,我们使用了一些工具来监测和操纵自由行为小鼠的神经活动,这些工具具有细胞类型特异性分辨率。我们发现Crf-BNST和Cck-BNST神经元分别向Hcrt-LH神经元提供丰富和稀疏的输入,对显著刺激显示离散的生理反应,驱动相反的情绪评价行为,并从上游网络接收不同比例的输入。总之,我们的数据提供了一个先进的模型,如何平行BNST->`LH途径促进不同的情绪状态,通过遗传定义的,电路特定的神经元亚群的连接模式。
Lateral hypothalamus (LH) neurons containing the neuropeptide hypocretin (Hcrt; orexin) modulate affective components of arousal, but their relevant synaptic inputs remain poorly defined. Here, we identified inputs onto LH neurons that originate from neuronal populations in the bed nuclei of stria terminalis (BNST; a heterogeneous region of extended amygdala). We characterized two non-overlapping LH-projecting GABAergic BNST subpopulations that express distinct neuropeptides (corticotropin-releasing factor; Crf, and cholecystokinin; Cck). To functionally interrogate BNST→LH circuitry, we used tools for monitoring and manipulating neural activity with cell-type-specific resolution in freely-behaving mice. We found that Crf-BNST and Cck-BNST neurons respectively provide abundant and sparse inputs onto Hcrt-LH neurons, display discrete physiological responses to salient stimuli, drive opposite emotionally valenced behaviors, and receive different proportions of inputs from upstream networks. Together, our data provide an advanced model for how parallel BNST->`LH pathways promote divergent emotional states via connectivity patterns of genetically defined, circuit-specific neuronal subpopulations.
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