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基底外侧杏仁核中表达 Thy1 的神经元促进了巩固、再巩固和消退过程中情境性恐惧的抑制。

Basolateral amygdala Thy1-expressing neurons facilitate the inhibition of contextual fear during consolidation, reconsolidation, and extinction.

机构信息

Department of Psychological Sciences and Brain Health Research Institute, 144 Kent Hall, Kent State University, Kent, OH 44242, USA.

出版信息

Neurobiol Learn Mem. 2018 Nov;155:498-507. doi: 10.1016/j.nlm.2018.09.010. Epub 2018 Oct 1.

Abstract

Disrupted fear inhibition is a characteristic of many anxiety disorders. Investigations into the neural mechanisms responsible for inhibiting fear will improve understanding of the essential circuits involved, and facilitate development of treatments that promote their activity. Within the basolateral amygdala (BLA), Thy1-expressing neuron activity has been characterized by us and others as promoting fear inhibition to discrete fear cues by influencing consolidation of cued fear learning or cued fear extinction. Here, we evaluated how activating BLA Thy1-expressing neurons using DREADDs affected the consolidation, expression, reconsolidation, and extinction of contextual fear. Using an inhibitory avoidance paradigm, our present findings indicate a similar involvement of BLA Thy1-expressing neuron activity in the consolidation and extinction, but not expression, of fear. Importantly, our data also provide the first evidence for involvement of these neurons in inhibiting fear reconsolidation. Therefore, these data enhance our understanding of the roles that Thy1-expressing neurons within the BLA play in inhibiting fear when examining avoidance, in addition to the already established role in Pavlovian fear paradigms. Future investigations should further explore the circuits responsible for these contextual effects modulated by BLA Thy1 neuron activation, and could promulgate development of therapies targeting these neurons and their downstream effectors.

摘要

恐惧抑制障碍是许多焦虑症的特征。对负责抑制恐惧的神经机制的研究将有助于更好地理解其中涉及的基本回路,并促进开发促进其活动的治疗方法。在基底外侧杏仁核 (BLA) 中,我们和其他人已经将表达 Thy1 的神经元活动的特征描述为通过影响条件性恐惧学习或条件性恐惧消退的巩固来促进对离散恐惧线索的恐惧抑制。在这里,我们评估了使用 DREADDs 激活 BLA 表达 Thy1 的神经元如何影响情境恐惧的巩固、表达、再巩固和消退。使用抑制性回避范式,我们目前的研究结果表明,BLA 表达 Thy1 的神经元活动在恐惧的巩固和消退中具有相似的作用,但在恐惧的表达中没有作用。重要的是,我们的数据还首次提供了证据,表明这些神经元参与抑制恐惧的再巩固。因此,这些数据增强了我们对 BLA 内表达 Thy1 的神经元在抑制回避时的恐惧的作用的理解,除了在巴甫洛夫恐惧范式中已经确立的作用。未来的研究应该进一步探索由 BLA Thy1 神经元激活调节的这些上下文效应的回路,并可能推动针对这些神经元及其下游效应物的治疗方法的开发。

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