皮层-丘脑的发育和疾病:从细胞到电路,再到精神分裂症。
Cortico-thalamic development and disease: From cells, to circuits, to schizophrenia.
发表日期:2023
作者:
Marilyn M Angulo Salavarria, Claudia Dell'Amico, Armando D'Agostino, Luciano Conti, Marco Onorati
来源:
Frontiers in Neuroanatomy
摘要:
人类大脑是在发育过程中生成的结构中最复杂的。揭示特定神经网络的发生和内在组织可能是理解不同脑区生理病理方面的关键。皮质-丘脑和丘脑-皮质(CT-TC)回路处理和调节诸如清醒、睡眠和记忆等基本任务,它们的改变可能导致神经发育和精神疾病。这些病理状况被报道影响特定神经群体,但也可能广泛改变生理连接,从而破坏脑网络的生成、通信和功能。更具体地说,据报道,CT-TC系统在影响上等脑功能的疾病如精神分裂症(SCZ)、双相情感障碍、自闭症谱系障碍或癫痫中受到严重影响。本文将重点探讨CT的发展,以及用于揭示和理解其分子和细胞机制的模型。除了动物模型外,仍然必不可少的揭示人类神经网络建立的工具,还将讨论诸如来源于人类多能干细胞的脑器官样结构以及组装体等先进的体外平台。这些器官样结构和组装体实际上代表了研究和促进CT发展及其功能障碍的基础研究的独特工具。然后,我们将讨论涉及CT-TC电路在生理和病理条件下产生连接图的发生、分化和功能的最新前沿研究,包括计算机模拟方法。版权所有 © 2023 Angulo Salavarria,Dell’Amico,D'Agostino,Conti和Onorati。
The human brain is the most complex structure generated during development. Unveiling the ontogenesis and the intrinsic organization of specific neural networks may represent a key to understanding the physio-pathological aspects of different brain areas. The cortico-thalamic and thalamo-cortical (CT-TC) circuits process and modulate essential tasks such as wakefulness, sleep and memory, and their alterations may result in neurodevelopmental and psychiatric disorders. These pathologies are reported to affect specific neural populations but may also broadly alter physiological connections and thus dysregulate brain network generation, communication, and function. More specifically, the CT-TC system is reported to be severely affected in disorders impacting superior brain functions, such as schizophrenia (SCZ), bipolar disorder, autism spectrum disorders or epilepsy. In this review, the focus will be on CT development, and the models exploited to uncover and comprehend its molecular and cellular mechanisms. In parallel to animal models, still fundamental to unveil human neural network establishment, advanced in vitro platforms, such as brain organoids derived from human pluripotent stem cells, will be discussed. Indeed, organoids and assembloids represent unique tools to study and accelerate fundamental research in CT development and its dysfunctions. We will then discuss recent cutting-edge contributions, including in silico approaches, concerning ontogenesis, specification, and function of the CT-TC circuitry that generates connectivity maps in physiological and pathological conditions.Copyright © 2023 Angulo Salavarria, Dell’Amico, D’Agostino, Conti and Onorati.