丘脑网状核PV和SOM神经元及其特定神经通路在全身麻醉意识消失过程中的作用研究

丘脑网状核（TRN）是调控意识形成的关键核团，阐明TRN在全麻意识消失过程中的作用是全麻机制研究的重要内容。TRN内GABA能神经元主要分为小清蛋白表达(PV)和生长抑素阳性(SOM)两种亚型，分别参与形成功能特定的神经通路。前期研究发现激活蓝斑-TRN通路加快全麻药丙泊酚的致意识消失过程，但尚不明确TRN内PV和SOM神经元及其特定神经通路在全麻意识消失中的具体作用。故本项目拟进一步 ① 利用活体光纤钙信号和神经递质荧光探针技术，检测丙泊酚麻醉中TRN内PV和SOM神经元活性和相应神经递质的变化；② 通过光遗传技术探明激活TRN内PV和SOM神经元及其特定上、下行神经通路对丙泊酚致意识消失作用的影响；③ 运用光遗传+脑片膜片钳技术深入阐明丙泊酚对TRN内PV和SOM神经元特定突触传递的作用机制。本项目将围绕TRN核团内神经元亚型及特定通路，为揭示全麻意识消失的机制提供靶点明确的实验依据。

Thalamic reticular nucleus (TRN) is a key nucleus that regulates the formation of consciousness. Understanding the role of TRN in the loss of consciousness during general anesthesia is an important content in the study of general anesthesia mechanism. The GABAergic neurons in TRN are mainly parvalbumin-expressing (PV) or somatostatin positive (SOM), which constructing specific neural pathways with specific functions. Our previous study found that activating the neural pathway from locus coeruleus to TRN can accelerate the process of loss of consciousness induced by propofol. However, the specific role of TRN PV and SOM neurons and related specific neural pathways in such process is not clear. Therefore, this project will use ① fiber-optic calcium signal recording and neurotransmitter fluorescence probe technology to detect the activity of PV and SOM neurons, and the change of corresponding neurotransmitters in TRN during propofol anesthesia. ② Optogenetic technology will be used to clarify the effects of activating these two types of neurons and their specific neural pathways on propofol anesthesia. ③ At the synaptic and molecular level, we will utilize optogenetic + patch-clamp technology to explore the specific action of propofol on the TRN PV and SOM neurons and their specific pathways. This project will support the mechanism exploration of anesthesia-induced unconscious at the level of subtypes of TRN neurons and related specific neural pathways.