中文摘要
大脑处理情感、学习、记忆等高级认知功能主要依赖于各类神经元以精密的连接方式组装成神经环路。神经环路的形成涉及一系列有序的细胞与细胞之间、细胞与外界微环境之间的相互作用以及依赖神经活动的突触调节。在大脑发育和成熟期,NG2胶质细胞,又称少突胶质前体细胞(OPC),不仅为形成神经元髓鞘的少突胶质细胞提供细胞来源,还能与谷氨酸能和γ-氨基丁酸能神经元直接形成突触联系。然而,这些突触联系的生理功能并不清楚。本项目将以处理学习、记忆的功能核团海马区为目的脑区,借助光电联合、化学遗传学、电生理学、钙成像、以及多种转基因小鼠行为学模型,通过在体激活、兴奋NG2胶质细胞,研究NG2细胞如何在海马的学习、记忆相关神经环路中参与对动物情感、学习记忆的功能调节,并从分子-突触-细胞-环路水平进行系统性解析NG2胶质细胞网络与神经元网络如何实现相互影响、相互对话,共同调节大脑认知行为功能的生理机制。
英文摘要
Emotion, learning and memory are the cognitive functions of the brain. It is dependent on a precise assembly of neural network and synaptic functions formed by neuronal activities, the interactions between neurons and microenvironments. NG2 glial cells, known as oligodendrocyte precursor cells (OPCs), represent a major pool of progenitors able to generate myelinating oligodendrocytes during the early development of the brain. In the adult mammalians, NG2 cells constitute a distinct large population of macroglials. NG2 cells have been reported to receive functional glutamatergic and GABAergic synapses mediating fast synaptic transmission in hippocampus. However, it remains largely unknown whether and how NG2 cells actively regulate neuronal activity, synaptic functions and plasticity, as well as their physiological relevance. We are utilizing a combination of techniques, including optogenetic and chemogenetic approaches, Ca2+ imaging in vitro and in vivo, AAV virus injection in vivo, electrophysiology and various genetic mouse models to investigate how NG2 glial cell-neuron interactions and their effects on the synaptic functions where finally leads to the learning and memory in the brain. The study should enrich our understanding of new mechanisms of how NG2 glial cells integrate into neural circuit involving of the learning and memory formation and modulation in the brain, which provides a theoretical and therapeutic target on the neurodegenerative diseases and mental disorders.
