抑制性神经元在大脑皮层慢波振荡中的功能作用

项目名称： 抑制性神经元在大脑皮层慢波振荡中的功能作用

项目编号： No.31471025

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 徐晗

作者单位： 浙江大学

项目金额： 93万元

中文摘要： 慢波振荡是动物慢波睡眠时脑电波最重要的特征并且与记忆巩固密切相关。慢波振荡起源于大脑皮层并且依赖兴奋性神经元和抑制性中间神经元相互连接而形成的神经网络。然而，慢波振荡的抑制性环路机制并不清楚。本项目将从抑制性神经元的新角度研究慢波振荡的神经机制。我们将利用转基因小鼠，结合离体和在体电生理记录技术，以及光遗传学技术，系统地研究主要类型抑制性神经元在慢波振荡中的活动规律，以及它们活动水平的改变对慢波振荡的直接影响，从而明确特定类型抑制性神经元在慢波振荡中的具体功能作用。鉴于患有神经精神疾病如精神分裂症、痴呆症等的病人常常伴有异常皮层慢波振荡活动，我们的研究结果不仅有助于理解大脑皮层慢波振荡形成的神经环路机制，对于揭示一些神经精神疾病的发病机理也具有重要意义。

中文关键词： 大脑皮层；抑制性神经元；慢波振荡；高电位期；光遗传学技术

英文摘要： Slow wave oscillations are the most prominent feature of slow wave sleep and are tightly linked to memory consolidation. Slow wave oscillations are generated within cortical neuronal networks of highly interconnected excitatory neurons and inhibitory interneurons. However, there is a large heterogeneity among inhibitory interneurons, and the precise roles played by different interneuron subtypes in slow wave oscillations are poorly understood. Combining electrophysiological and optogenetic approaches with the availability of mouse lines expressing Cre in specific subtypes of inhibitory interneurons, we will systematically study the functional roles of inhibitory interneuron subtypes in cortical slow wave oscillations both in vitro and in vivo. First, we will investigate the functional correlations between the activity of inhibitory interneuron subtypes (such as PV interneruons, SOM interneurons, VIP interneurons) and specific features of slow wave oscillations (such as the amplitude and the duration of UP states). For the inhibitory interneuron subtypes that show strong correlations with slow wave oscillations, we will further investigate the impact of their activation or inactivation on specific features of slow wave oscillations. Together, the studies will help understand the inhibitory circuit mechanisms underlying cortical slow wave oscillations. Given that abnormal cortical slow wave oscillations and dysfunctions in inhibitory interneurons are often implicated in neuropsychiatric diseases such as schizophrenia and dementia, the findings from our proposed studies will also advance the development of future therapies for brain disorders.

英文关键词： cerebral cortex;inhibitory neurons;slow wave oscillations;UP states;optogenetics