Genetic dissection of an amygdala microcircuit that gates conditioned fear.

Genetic dissection of an amygdala microcircuit that gates conditioned fear.
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DOI:
10.1038/nature09553
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发表时间:
2010-11-11
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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不同的杏仁核(神经解剖学细分)在处理巴甫洛夫条件性恐惧的作用已被广泛研究,但这些核内的异质神经元亚型的功能仍然知之甚少。我们使用分子遗传学方法来定位位于中央杏仁核(CE 1)外侧亚区的GABA能神经元亚群的功能连接,该亚群表达蛋白激酶C-δ(PKCδ)。杏仁核切片中的视紫红质-2辅助回路映射和细胞特异性病毒示踪表明,PKCδ+神经元抑制内侧CE(CEm)的输出神经元,并且还与CE 1中的PKCδ−神经元形成相互抑制性突触。体内PKCδ+神经元的电沉默表明,它们对应于被条件刺激(CS)抑制的生理学上鉴定的单位,称为CEloff单位(Ciocchi等人,本期)。这种对应关系与行为数据一起定义了CEl中的抑制性微电路,其门控CEm输出以控制条件冻结的水平。
The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. We used molecular genetic approaches to map the functional connectivity of a subpopulation of GABAergic neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-delta (PKCδ). Channelrhodopsin-2 assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKCδ+ neurons inhibit output neurons in the medial CE (CEm), and also make reciprocal inhibitory synapses with PKCδ− neurons in CEl. Electrical silencing of PKCδ+ neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus (CS), called CEloff units (Ciocchi et al, this issue). This correspondence, together with behavioral data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.
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