中文摘要
GABA能神经元在保证大脑皮层正常执行各种功能活动中具有重要作用。按不同分子标志物,GABA能神经元还分为很多亚类,主要有parvalbumin, cholecystokinin, somatostatin, calretinin阳性神经元等。不同类型GABA能神经元在发育和功能等方面具有高度多样性, 提示它们在大脑皮层信息处理和各种高级脑功能中发挥不同作用。然而, 过去人们对不同类GABA能神经元的发育特点和功能调控知之甚少。近几年我们实验室研究了前额叶皮层parvalbumin阳性神经元的发育和功能。接下来,我们将综合运用光学遗传学、电生理和显微成像等技术系统研究其它三种GABA能神经元的发育和神经调节素1对其功能的调控,阐明不同种类GABA能神经元的发育特点、功能调控以及在前额叶皮层高级认知和情感中的作用,也为人们理解GABA能神经元发育和功能异常相关的神经精神类疾病提供新的思路。
英文摘要
GABAergic neruons, which use GABA as their transmitter and comprise about 20% of all neurons in the neocortex, are an important premise for executing all kinds of brain functions. GABAergic neurons have been subdivided into many subtypes based on specific biomarkers, including mainly parvalbumin-, cholecystokinin-, somatostatin-, and calretinin-positive neurons that are distinct in terms of development, morphology, physiology, synaptic connection, and firing patterns. This suggests that different subtypes of GABAergic neurons may play different roles in information processing and many high-order cognitive functions. However, little has been known about the development and functional regulation of each subtypes of GABAergic neurons due to the lack of specific markers to distinguish them. Recently, with the advent of new techniques, it has become possible to study the development and functional regulation of different subtypes of GABAergic neurons. In the past few years, we have studied the development and function of parvalbumin-positive neurons; thus, with a combination of both in vitro and in vivo electrophysiology, optogenetics, and immunofluorescent microscopy, we next will systematically study the development and neuregulin1-mediated functional regulation of three major non-parvalbumin GABAergic neurons, i.e. cholecystokinin-, somatostatin-, and calretinin-positive GABAergic neurons. This study will add to our knowledge of the development and functional regulation of different subtypes of GABAergic neurons, help to shed light on the biological functions of these neurons in cognition and emotion, and provide new clew for understanding the mechanisms behind developmental neuropsychiatric disorders associated with GABAergic dysfunction.
