星形胶质细胞对发育中大脑皮层神经环路结构和功能的调控研究

The cerebral cortex is the highest order of the brain that receives and processes sensory information. Astrocytes are the most abundant type of glial cells in the cerebral cortex. Emerging evidence suggests that astrocytes can directly or indirectly regulate neuronal activities, which makes them important to modulate different aspects of cortical functions. However, our knowledge is still very limited on the roles for astrocytes at circuit-level, especially on how astrocytes modulate the organization and function of cortical circuits during development. In the present study, it is proposed that astrocytes play a pivotal role in the organization and refinement of cortical circuits during early development. Combining multiple approaches such as optogenetics, confocal microscopy and electrophysiology, we will explore the spatial and temporal profile of astrocytes, as well as the effects of astrocytes on the plasticity of cortical circuits during early postnatal development. This line of research will lead us to better understanding of the mechanisms underlying the establishment and rewiring of cortical circuits, therefore provide theoretical and experimental evidence for developing higher-level artificial intelligence and finding new strategies for clinical treatment of neurological diseases related to cortical deficits.

大脑皮层是接受并处理感觉信息的最高级中枢。星形胶质细胞是大脑皮层中数量最为丰富的一类神经胶质细胞。新的证据表明，星形胶质细胞能够直接或间接的影响神经元的活动，从而调控大脑皮层的多种功能。然而, 目前在神经环路水平对于星形胶质细胞作用的认知还很局限，尤其是对发育过程中星形胶质细胞在大脑皮层神经环路的结构和功能调控中所扮演的角色尚不清楚。因此，本项目组假设星形胶质细胞对早期发育阶段大脑皮层神经环路的建立和精细调控具有重要作用。我们将综合应用光遗传学、共聚焦成像和电生理等多项技术，系统研究出生后早期星形胶质细胞自身在大脑皮层的时空发育轨迹，以及星形胶质细胞对发育期皮层神经环路组成结构和可塑性的影响。本项目的完成将有助于我们更全面的理解大脑皮层神经环路的构建和重塑机制，从而为开发更高级别的人工智能以及在临床上治疗与大脑皮层功能缺陷相关的神经系统疾病提供坚实的理论依据和实验基础。

星形胶质细胞是大脑皮层中数量最为丰富的一类神经胶质细胞，能够通过对神经元活动直接或间接的作用而参与调控大脑皮层的多种功能。已知出生后早期发育阶段大脑皮层神经元具有显著的经验依赖可塑性，这也被认为是皮层神经微环路在发育关键期进行精细化调控的重要机制之一。然而，星形胶质细胞是否也同样、以及如何参与早期发育阶段神经微环路的精细化调控还不清楚。. 本项目首先通过免疫荧光标记和共聚焦成像，阐明了出生后早期星形胶质细胞在大脑皮层中的时空发育轨迹；随后通过脑片电生理记录，明确了星形胶质细胞与周围神经元，以及星形胶质细胞之间的功能连接特性。此外，本项目还发现星形胶质细胞的数量、生理特性和连接特性可以被发育关键期中不同模式的感觉经验调控所影响，从而提示星形胶质细胞不仅也具有类似于神经元的可塑性，并且可能通过这些可塑性参与神经微环路的精细化调控。. 综上所述，本项目的研究成果有助于我们更加全面的理解包括胶质细胞在内的大脑皮层神经微环路的精细化调控机制。我们的实验结果也为进行更接近真实大脑网络的具有生物学可解释性的人工智能算法开发提供了丰富的基础数据。.