Wang Jun, Tian Yuanyuan, Zeng Ling-Hui, Xu Han
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
Front Cell Neurosci. 2020 Dec 17;14:611732. doi: 10.3389/fncel.2020.611732. eCollection 2020.
Social fear and avoidance of social partners and social situations represent the core behavioral symptom of Social Anxiety Disorder (SAD), a prevalent psychiatric disorder worldwide. The pathological mechanism of SAD remains elusive and there are no specific and satisfactory therapeutic options currently available. With the development of appropriate animal models, growing studies start to unravel neuronal circuit mechanisms underlying social fear, and underscore a fundamental role of the prefrontal cortex (PFC). Prefrontal cortical functions are implemented by a finely wired microcircuit composed of excitatory principal neurons (PNs) and diverse subtypes of inhibitory interneurons (INs). Disinhibition, defined as a break in inhibition interactions between IN subtypes that enhances the output of excitatory PNs, has recently been discovered to serve as an efficient strategy in cortical information processing. Here, we review the rodent animal models of social fear, the prefrontal IN diversity, and their circuits with a particular emphasis on a novel disinhibitory microcircuit mediated by somatostatin-expressing INs in gating social fear behavior. The INs subtype distinct and microcircuit-based mechanism advances our understanding of the etiology of social fear and sheds light on developing future treatment of neuropsychiatric disorders associated with social fear.
社交恐惧以及对社交伙伴和社交场合的回避是社交焦虑障碍（SAD）的核心行为症状，SAD是一种在全球范围内普遍存在的精神疾病。SAD的病理机制仍不清楚，目前也没有特效且令人满意的治疗方法。随着合适动物模型的建立，越来越多的研究开始揭示社交恐惧背后的神经回路机制，并强调前额叶皮层（PFC）的重要作用。前额叶皮层的功能由一个精细连接的微回路实现，该微回路由兴奋性主神经元（PNs）和多种抑制性中间神经元（INs）亚型组成。去抑制作用，即中间神经元亚型之间抑制性相互作用的中断，增强了兴奋性主神经元的输出，最近被发现是皮层信息处理中的一种有效策略。在这里，我们综述了社交恐惧的啮齿动物模型、前额叶中间神经元的多样性及其回路，特别强调了由表达生长抑素的中间神经元介导的一种新型去抑制微回路在控制社交恐惧行为中的作用。中间神经元亚型的差异和基于微回路的机制增进了我们对社交恐惧病因的理解，并为开发与社交恐惧相关的神经精神疾病的未来治疗方法提供了思路。
