岛叶皮层突触可塑性的非经典离子通道机制

项目名称： 岛叶皮层突触可塑性的非经典离子通道机制

项目编号： No.31500834

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 神经、认识与心理学

项目作者： 刘明刚

作者单位： 上海交通大学

项目金额： 20万元

中文摘要： 岛叶皮层是哺乳动物脑内一个重要结构，参与诸多生理功能和疾病过程。申请人长期致力于岛叶皮层突触可塑性研究，率先在成年小鼠的岛叶皮层成功诱导长时程增强（LTP）和长时程抑制（LTD），但这些突触可塑性的形成机制和功能意义有待进一步研究。酸敏感离子通道（ASIC）是一类由胞外质子激活的阳离子通道，在大脑皮层高表达，并且已有证据表明ASIC亚基1a基因敲除损害海马皮层LTP，但ASIC1a是否以及如何影响岛叶皮层LTP和LTD尚未见文献报道。本项目拟运用常规和岛叶皮层条件性基因敲除、药理学、病毒携带基因干预/解救、脑片膜片钳、离体多通道阵列记录分析、生物化学与分子生物学等多种技术手段，研究ASIC在岛叶皮层的表达定位及其对岛叶基础突触传递以及突触可塑性的影响，并揭示ASIC1a贡献岛叶突触可塑性的分子机制,为进一步阐明岛叶突触可塑性的发生机理提供新思路,也为加深理解ASIC的生理功能提供新依据。

中文关键词： 岛叶皮层；突触可塑性；非经典离子通道；多电极阵列记录

英文摘要： Insular cortex is an important forebrain structure involved in several sensory and cognitive functions and dysfunctions, such as pain perception, taste memory, self-awareness and drug addiction. Our previous work shows that insular synapses could undergo typical forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), which might set the synaptic basis for the above behaviors mediated by the insular cortex. However, the detailed signaling pathways underlying insular synaptic plasticity are still not clear. The acid-sensing ion channels (ASICs) are widely expressed in the CNS, and there is evidence indicating that ASIC1a has a role in hippocampal LTP. However, no information is available on the contribution of ASIC1a to insular synaptic transmission and plasticity. The present project was aimed to address this issue through a combination of several neurobiological techniques, such as patch-clamp, multi-electrode array recording, viral genetics, genetically-engineered mice, biochemistry and molecular biology. Specifically, we will focus on the following four research contents: (1) expression and distribution of ASICs in the insular cortex; (2) effects of ASIC1a on basal synaptic efficacy and intrinsic excitability; (3) roles of ASIC1a in multiple forms of insular synaptic plasticity; (4) signaling mechanisms underlying the ASIC1a-dependent insular plasticity. These studies are expected to shed novel insights into the precise ionic mechanisms of synaptic plasticity in the insular cortex, as well as providing the molecular explanation on the physiological functions of ASICs.

英文关键词： insular cortex;synaptic plasticity;non-classical ion channel;multi-electrode array recording