Department of Molecular Neurobiology, Donders Institute for Brain, Cognition and Behaviour and Faculty of Science, Radboud University, Nijmegen, The Netherlands.
Department of Neuroscience and Kavli Institute for Neuroscience, Yale University, New Haven, Connecticut, USA.
Neuropsychopharmacology. 2022 Jan;47(1):41-57. doi: 10.1038/s41386-021-01137-9. Epub 2021 Oct 13.
During evolution, the cerebral cortex advances by increasing in surface and the introduction of new cytoarchitectonic areas among which the prefrontal cortex (PFC) is considered to be the substrate of highest cognitive functions. Although neurons of the PFC are generated before birth, the differentiation of its neurons and development of synaptic connections in humans extend to the 3rd decade of life. During this period, synapses as well as neurotransmitter systems including their receptors and transporters, are initially overproduced followed by selective elimination. Advanced methods applied to human and animal models, enable investigation of the cellular mechanisms and role of specific genes, non-coding regulatory elements and signaling molecules in control of prefrontal neuronal production and phenotypic fate, as well as neuronal migration to establish layering of the PFC. Likewise, various genetic approaches in combination with functional assays and immunohistochemical and imaging methods reveal roles of neurotransmitter systems during maturation of the PFC. Disruption, or even a slight slowing of the rate of neuronal production, migration and synaptogenesis by genetic or environmental factors, can induce gross as well as subtle changes that eventually can lead to cognitive impairment. An understanding of the development and evolution of the PFC provide insight into the pathogenesis and treatment of congenital neuropsychiatric diseases as well as idiopathic developmental disorders that cause intellectual disabilities.
在进化过程中，大脑皮层通过增加表面积和引入新的细胞构筑区域来发展，其中前额叶皮层（PFC）被认为是最高认知功能的基础。尽管 PFC 的神经元在出生前就已经产生，但它们的神经元分化和突触连接的发育在人类中一直延伸到 30 岁。在此期间，突触以及包括其受体和转运体在内的神经递质系统最初会过度产生，然后选择性消除。应用于人类和动物模型的先进方法，使我们能够研究特定基因、非编码调节元件和信号分子在控制前额叶神经元产生和表型命运以及神经元迁移以建立 PFC 分层中的细胞机制和作用。同样，各种遗传方法与功能测定以及免疫组织化学和成像方法相结合，揭示了神经递质系统在 PFC 成熟过程中的作用。遗传或环境因素对神经元产生、迁移和突触发生的干扰，甚至是轻微的减缓，都可能导致明显或微妙的变化，最终导致认知障碍。对 PFC 发育和进化的理解为先天性神经精神疾病以及导致智力障碍的特发性发育障碍的发病机制和治疗提供了深入的了解。
