大脑进化中的抑制系统：神经发育障碍的易感性途径
Inhibitory Systems in Brain Evolution: Pathways of Vulnerability in Neurodevelopmental Disorders.
作者信息
Hanson Kari L, Greiner Demi M Z, Schumann Cynthia M, Semendeferi Katerina
机构信息
Department of Psychiatry and Behavioral Sciences, UC Davis School of Medicine, Sacramento, California, USA.
MIND Institute, UC Davis School of Medicine, Sacramento, California, USA.
出版信息
Brain Behav Evol. 2025;100(1):29-48. doi: 10.1159/000540865. Epub 2024 Aug 13.
BACKGROUND
The evolution of the primate brain has been characterized by the reorganization of key structures and circuits underlying derived specializations in sensory systems, as well as social behavior and cognition. Among these, expansion and elaboration of the prefrontal cortex has been accompanied by alterations to the connectivity and organization of subcortical structures, including the striatum and amygdala, underlying advanced aspects of executive function, inhibitory behavioral control, and socioemotional cognition seen in our lineages. At the cellular level, the primate brain has further seen an increase in the diversity and number of inhibitory GABAergic interneurons. A prevailing hypothesis holds that disruptions in the balance of excitatory to inhibitory activity in the brain underlies the pathophysiology of many neurodevelopmental and psychiatric disorders.
SUMMARY
This review highlights the evolution of inhibitory brain systems and circuits and suggests that recent evolutionary modifications to GABAergic circuitry may provide the substrate for vulnerability to aberrant neurodevelopment. We further discuss how modifications to primate and human social organization and life history may shape brain development in ways that contribute to neurodivergence and the origins of neurodevelopmental disorders.
KEY MESSAGES
Many brain systems have seen functional reorganization in the mammalian, primate, and human brain. Alterations to inhibitory circuitry in frontostriatal and frontoamygdalar systems support changes in social behavior and cognition. Increased complexity of inhibitory systems may underlie vulnerabilities to neurodevelopmental and psychiatric disorders, including autism and schizophrenia. Changes observed in Williams syndrome may further elucidate the mechanisms by which alterations in inhibitory systems lead to changes in behavior and cognition. Developmental processes, including altered neuroimmune function and age-related vulnerability of inhibitory cells and synapses, may lead to worsening symptomatology in neurodevelopmental and psychiatric disorders.
BACKGROUND
The evolution of the primate brain has been characterized by the reorganization of key structures and circuits underlying derived specializations in sensory systems, as well as social behavior and cognition. Among these, expansion and elaboration of the prefrontal cortex has been accompanied by alterations to the connectivity and organization of subcortical structures, including the striatum and amygdala, underlying advanced aspects of executive function, inhibitory behavioral control, and socioemotional cognition seen in our lineages. At the cellular level, the primate brain has further seen an increase in the diversity and number of inhibitory GABAergic interneurons. A prevailing hypothesis holds that disruptions in the balance of excitatory to inhibitory activity in the brain underlies the pathophysiology of many neurodevelopmental and psychiatric disorders.
SUMMARY
This review highlights the evolution of inhibitory brain systems and circuits and suggests that recent evolutionary modifications to GABAergic circuitry may provide the substrate for vulnerability to aberrant neurodevelopment. We further discuss how modifications to primate and human social organization and life history may shape brain development in ways that contribute to neurodivergence and the origins of neurodevelopmental disorders.
KEY MESSAGES
Many brain systems have seen functional reorganization in the mammalian, primate, and human brain. Alterations to inhibitory circuitry in frontostriatal and frontoamygdalar systems support changes in social behavior and cognition. Increased complexity of inhibitory systems may underlie vulnerabilities to neurodevelopmental and psychiatric disorders, including autism and schizophrenia. Changes observed in Williams syndrome may further elucidate the mechanisms by which alterations in inhibitory systems lead to changes in behavior and cognition. Developmental processes, including altered neuroimmune function and age-related vulnerability of inhibitory cells and synapses, may lead to worsening symptomatology in neurodevelopmental and psychiatric disorders.
背景
灵长类大脑的进化特征是感觉系统、社会行为和认知等衍生特化所依赖的关键结构和回路发生重组。其中，前额叶皮层的扩展和精细化伴随着皮层下结构（包括纹状体和杏仁核）的连接性和组织的改变，这些结构支撑着我们谱系中所具有的执行功能、抑制性行为控制和社会情感认知等高级功能。在细胞水平上，灵长类大脑中抑制性γ-氨基丁酸（GABA）能中间神经元的多样性和数量进一步增加。一个普遍的假说是，大脑中兴奋性与抑制性活动平衡的破坏是许多神经发育和精神疾病病理生理学的基础。
总结
本综述强调了抑制性脑系统和回路的进化，并指出最近对GABA能回路的进化改变可能为异常神经发育的易感性提供了基础。我们进一步讨论了灵长类和人类社会组织及生活史的改变如何以促进神经差异和神经发育障碍起源的方式塑造大脑发育。
关键信息
许多脑系统在哺乳动物、灵长类和人类大脑中都经历了功能重组。前额叶纹状体和前额叶杏仁核系统中抑制性回路的改变支持了社会行为和认知的变化。抑制系统复杂性的增加可能是包括自闭症和精神分裂症在内的神经发育和精神疾病易感性的基础。威廉姆斯综合征中观察到的变化可能进一步阐明抑制系统改变导致行为和认知变化的机制。发育过程，包括神经免疫功能的改变以及抑制性细胞和突触与年龄相关的易损性，可能导致神经发育和精神疾病症状的恶化。
背景
灵长类大脑的进化特征是感觉系统、社会行为和认知等衍生特化所依赖的关键结构和回路发生重组。其中，前额叶皮层的扩展和精细化伴随着皮层下结构（包括纹状体和杏仁核）的连接性和组织的改变，这些结构支撑着我们谱系中所具有的执行功能、抑制性行为控制和社会情感认知等高级功能。在细胞水平上，灵长类大脑中抑制性γ-氨基丁酸（GABA）能中间神经元的多样性和数量进一步增加。一个普遍的假说是，大脑中兴奋性与抑制性活动平衡的破坏是许多神经发育和精神疾病病理生理学的基础。
总结
本综述强调了抑制性脑系统和回路的进化，并指出最近对GABA能回路的进化改变可能为异常神经发育的易感性提供了基础。我们进一步讨论了灵长类和人类社会组织及生活史的改变如何以促进神经差异和神经发育障碍起源的方式塑造大脑发育。
关键信息
许多脑系统在哺乳动物、灵长类和人类大脑中都经历了功能重组。前额叶纹状体和前额叶杏仁核系统中抑制性回路的改变支持了社会行为和认知的变化。抑制系统复杂性的增加可能是包括自闭症和精神分裂症在内的神经发育和精神疾病易感性的基础。威廉姆斯综合征中观察到的变化可能进一步阐明抑制系统改变导致行为和认知变化的机制。发育过程，包括神经免疫功能的改变以及抑制性细胞和突触与年龄相关的易损性，可能导致神经发育和精神疾病症状的恶化。
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