焦虑是帕金森病（PD）的一个重要的非运动症状。我们发现基底外侧杏仁核（BLA）中5-HT6受体能调节PD大鼠的焦虑行为,为研究其机制，我们拟采用光遗传学方法，将CaMKⅡα启动子控制的携带ChR2/eNpHR3.0-YFP的慢病毒载体转染、表达至PD大鼠BLA内谷氨酸能神经元及其神经末梢，分别对BLA—中央杏仁核外侧部（CeL）—内侧部（CeM）环路中谷氨酸能神经元胞体及神经末梢给予光刺激，结合神经药理学手段，激活/阻断BLA内5-HT6 受体，应用行为学、脑片膜片钳、多通道电生理、微透析及形态学等方法，检测大鼠的焦虑行为、BLA-CeL-CeM环路中神经元的电生理特性、细胞外谷氨酸、GABA和单胺类递质水平、细胞活化（c-fos表达）范围；揭示该环路在PD状态下的功能改变与焦虑发病的关系，并阐明BLA内5-HT6受体对该环路介导的PD焦虑的调控机制。以期从新的角度揭示PD焦虑的发病机制。

Anxiety is considered as an increased risk factor for Parkinson’s disease (PD). Previous studies from our laboratory have found that inhibition of 5-HT6 receptor in the BLA produced anxiolytic effects in the PD model of rats, whereas activation of 5-HT6 receptors in the BLA induced anxiety-like responses. At present, there are no studies that have investigated the modulatory mechanism of 5-HT6 receptor on BLA-CeL-CeM circuitry mediated anxiety in PD. Therefore, this project will be performed on rats with 6-hydroxydopamine lesions of the medial forebrain bundle (MFB). Lentiviral vectors carrying the ChR2/eNpHR3.0-YFP fusion gene under control of the CaMKⅡαpromoter, to target glutamatergic neuron in BLA, will be constructed using standard cloning techniques. We aim to apply optogenetic technique on precise activation of rat BLA/CeA. To investigate the underlying mechanism of the BLA-CeL-CeM pathway in the rat model of PD in anxiety, we will probe freely moving rats under projection-specific optogenetic control, multi-channel in vivo recording techniques will be used to observe and record the firing patterns of the BLA, CeL and CeM neurons, and the microdialysis method will be used to quantify the extracellular GABA、Glu、DA、5-HT、NA levels in the open field and the elevated-plus maze tests. To track neuronal activation, we will use activity-dependent immediate early gene (c-fos) expression, and then quantify the proportion of neurons in the BLA, CeL and CeM within each group that expressed eYFP or showed c-fos immunoreactivity. Whole-cell patch-clamp electrophysiology with two-photon imaging will be combined to visualize the microcircuit while simultaneously probing the functional relationships among BLA/CeL/CeM neurons during projection-specific optogenetic control. To illustrate the modulatory mechanism of the 5-HT6 receptor on the BLA-CeL-CeM pathway mediated anxiety in the rat model of PD, the 5-HT6 receptor in the BLA will be activated or blocked, and the changes in anxiety behavior, activation range of amygdala neurons, neurotransmitter levels, and the electrophysiological properties under different methods will be detected as above. These findings will reveal the pathogenesis of anxiety in PD.