Biologically based neural circuit modelling for the study of fear learning and extinction.
Biologically based neural circuit modelling for the study of fear learning and extinction.
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DOI：
10.1038/npjscilearn.2016.15
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发表时间：
2016-01-01
影响因子：
4.2
通讯作者：
Vicentic, Aleksandra
中科院分区：
文献类型：
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作者：
Nair, Satish S;Pare, Denis;Vicentic, Aleksandra
促进保护性防御行为的神经系统已被广泛研究使用巴甫洛夫条件反射。在这个范例中，一个最初的中性条件刺激与一个厌恶的非条件刺激配对，导致受试者表现出恐惧的行为迹象。几十年来对这种简单行为模式的神经基础的研究发现，杏仁核是一个由几个相互连接的核组成的复杂结构，是恐惧记忆获得、巩固和表达所需的神经回路的重要组成部分。然而，电生理学、神经束示踪、影像学、分子、光遗传学和化学遗传学等新发现的证据表明，恐惧学习是由多个杏仁核与其分布靶点之间的多重连接、局部回路元件可塑性的动态变化以及促进突触可塑性的神经调节机制介导的。为了揭示这些复杂的关系并分析从这些研究中获得的多模态数据集，我们认为生物学上现实的计算模型与实验相结合，提供了一个机会，可以促进我们对恐惧学习的神经回路机制的理解，并解决它们的功能障碍如何导致精神障碍患者的适应不良恐惧反应。
The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.