精神分裂症易感因子ErbB4对篮状细胞和吊灯状细胞神经环路发育的调控和机制

项目名称： 精神分裂症易感因子ErbB4对篮状细胞和吊灯状细胞神经环路发育的调控和机制

项目编号： No.81471150

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： 杨建明

作者单位： 浙江大学

项目金额： 70万元

中文摘要： 精神分裂症是一种遗传和环境因素共同作用下中枢神经环路发育异常的严重的神经精神类疾病。大量研究表明，ErbB4是精神分裂症易感因子。然而，其导致患精神分裂症的病理机制并不清楚。最近我们研究发现ErbB4调控皮层PV中间神经元环路发育和功能。PV神经元环路发育和功能异常是精神分裂症核心病理机制之一。然而，PV神经元还分为篮状细胞和吊灯状细胞，二者形态迥异，且分别在工作记忆和多种高级认知功能中起不同的重要作用。因此，我们结合在体与离体电生理、光遗传学、药理学、动物行为学和免疫荧光显微成像等技术，从细胞、环路、系统和整体等多水平研究ErbB4通过调控PV篮状细胞和吊灯状细胞神经环路发育参与精神分裂症发病的环路发育机制，该研究不仅有助于增加人们对篮状细胞和吊灯状细胞神经环路发育的认识，同时也有助于阐明ErbB4通过调控篮状细胞和吊灯状细胞神经环路发育参与精神分裂症发病的机制。

中文关键词： 发育；神经环路；中间神经元；大脑皮层；精神分裂症

英文摘要： Schizophrenia is a severe developmental neuropsychiatric disorder caused by both genetic and environmental risk factors. Many studies showed that erbb4 is a susceptibility gene for schizophrenia. However, the underlying mechanisms are largely unknown. Our recent works showed that ErbB4 signals regulate the development and functions of neural circuits formed by parvalbumin (PV) interneurons. Abnormal PV neural circuit development and functions may thus represent a pathological entity of schizophrenia. However, PV neurons comprise basket and chandelier cells that are morphologically distinct and play important yet different roles during working memory and may other high-order cognitive functions. Here, with a combination of both in vitro and in vivo electrophysiology, optogenetics, pharmacology, animal behavior tests and immunofluorescent microscopy, we will study the mechanisms of ErbB4 signals in schizophrenia during the development of neural circuits formed by basket and chandelier cells from multiple levels. Our study will add to our knowledge of the development of neural circuits formed by basket and chandelier cells, and further improve our understanding of the biological functions of ErbB4-regulated neural circuits involved in schizophrenia.

英文关键词： development;neural circuitry;interneurons;neocortex;schizophrenia