基于猕猴模型研究精神分裂症中工作记忆损伤的神经网络机制

项目名称： 基于猕猴模型研究精神分裂症中工作记忆损伤的神经网络机制

项目编号： No.81471368

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 余山

作者单位： 中国科学院自动化研究所

项目金额： 70万元

中文摘要： 精神分裂症的一个核心症状是工作记忆损伤，由此引起一系列高级认知功能的降低。全面认识精神分裂症中工作记忆损伤的神经机制，是寻求更有效治疗手段的一个重要前提。目前对于这一机制的了解还局限于神经递质以及单个神经元水平，对于工作记忆至关重要的神经网络活动在精神分裂症中受到什么影响还远未明了。本项目计划用猕猴作为精神分裂症的动物模型，通过比较正常对照组和精神分裂症模型组动物的工作记忆能力及背外侧前额叶神经网络活动的差异，系统化的研究精神分裂症中工作记忆损伤的网络机制。特别地，我们将验证目前流行的兴奋/抑制失衡假说，并研究如何恢复前额叶兴奋/抑制来改善受损的工作记忆能力。本课题将结合先进的在体高密度微电极阵列纪录技术与新发展的临界态分析方法，有望作出一系列高水平的研究成果，从而揭示工作记忆在精神分裂症中损伤的神经网络机制，为治疗精神分裂症的工作记忆损伤提供新的依据和思路。

中文关键词： 精神分裂症；前额叶皮层；工作记忆；神经网络；猕猴

英文摘要： One of the core symptoms for Schizophrenia is the deficit in working memory (WM), which is the cause for a series of cognitive impairments associated with Schizophrenia. Understanding the neuronal mechanisms underlying such deficit is of great importance for seeking more effective treatments to mitigate cognitive impairments in Schizophrenia. So far related studies have been focused at the level of individual neurons or aspects related to neuromodulation, leaving the impact of Schizophrenia on activities of neural network unclear, which are, however, the essential component for carrying out WM fcuntion. In this study, we plan to use rhesus monkeys as a animal model for Schizophrenia. By comparing the differences in both WM function as well as the network activities in the dorsal lateral prefrontal cortex while animals are performing WM tasks, we expect to uncover the mechanisms at the neural network level that mediate the deficit in WM observed in Schizophrenia. Specifically, we will test the popular hypothesis of the imbalance between excitation (E) and inhibition (I) at the network level in Schizophrenia and, furthermore,investigate how to restore the E/I balance in order to rescue the impaired WM function. To this end, we will combine the state-of-art technology in making highly parallel recordings in vivo with advanced theoretical/analytical framework of network criticality. The anticipated results will provide new insights into network mechanisms underlying the cognitive impairments in Schizophrenia and, at the same time, open new opportunities for better treating such impairments.

英文关键词： Schizophrenia;Prefrontal cortex;Working memeory;Neural network;Rhesus monkey