树鼩内侧前额叶皮层情绪编码模式及其投射环路

The medial prefrontal cortex (mPFC) plays an essential role in the regulation of emotions. Tree shrews are closely related to primates in cellular organization of the mPFC. However, the encoding patterns and neural circuits of diverse emotions in the mPFC of tree shrews remain unclear. In our preliminary experiments, we found that numerous neurons in the mPFC encoded aversive emotion and projected to the bed nucleus of stria terminalis. The mPFC, accumbens nucleus, bed nucleus of stria terminalis and amygdala are important components of emotion-related neural circuits. Thus, we hypothesize that external pleasant and aversive stimuli might activate neurons in the mPFC and mPFC-innervated brain regions of tree shrews. The characteristics of distribution, morphology and calcium signals of these neurons might represent the encoding schemes of corresponding emotions. In this project, tyramide-amplified immunohistochemistry- fluorescence in situ hybridization (TAI-FISH) will be applied to identify the distribution of emotional encoding neurons in the mPFC and mPFC-innervated brain regions at single-cell resolution. Quantitative analysis will be used to analyze the synaptic morphology and calcium dynamics in time and space of encoding and non-encoding neurons in these brain regions. By excitotoxic inhibition and optogenetic manipulation of neural activity in the mPFC, we aim to investigate the effect of the mPFC on the emotional encoding patterns in the accumbens nucleus, bed nucleus of stria terminalis and amygdala as well as pleasant and aversive behaviors. Finally, we hopefully elucidate the emotional encoding schemes of the mPFC and mPFC-innervated brain regions and the role of these regions in response to emotional stimuli in tree shrews.

内侧前额叶皮层（mPFC）在情绪调节中起关键作用。树鼩mPFC的细胞构筑更接近灵长类，但是其对不同情绪的编码模式及其投射环路还不清楚。我们前期预实验发现树鼩mPFC中有大量编码厌恶情绪的神经元并投射至终纹床核。mPFC、伏核、终纹床核、杏仁核等是情绪神经环路的重要组成部分。由此假设：当遇到外界快感和厌恶刺激时，会迅速激活树鼩mPFC及其投射脑区中的神经元，这些神经元的分布特点、形态特征和钙信号特性代表着相应脑区中情绪的编码模式。本研究拟采用最新的TAI-FISH技术在单细胞水平上鉴定mPFC及其投射脑区中编码情绪的神经元分布模式；进一步对这些脑区中编码和非编码情绪神经元的突触形态可塑性和钙信号时空特性进行定量分析；通过兴奋毒素抑制和光遗传学操控mPFC活性研究其对伏核、终纹床核和杏仁核中情绪编码模式和快感或厌恶行为的影响。期望阐述树鼩mPFC及其投射环路的情绪编码模式和在情绪反应中作用。

内侧前额叶皮层（mPFC）在情绪调节中起关键作用，树鼩的mPFC与终纹床核（BST）、下丘脑和杏仁核等脑区联系密切。本课题主要研究树鼩mPFC及其投射环路的情绪编码模式和在情绪反应中作用。主要研究结果如下：（1）完成了《树鼩脑立体定位图谱》（英文版）一书：书中包括192幅冠状面彩图、36幅矢状面彩图、49幅水平面彩图和若干核磁共振黑白图，本图谱是目前最系统、最全面的树鼩全脑解剖专著，有助于国内外同行获取更加精准的树鼩脑核团定位，促进树鼩脑科学的研究。（2）鉴定了mPFC及其投射脑区中的神经元编码模式：验证了BST受mPFC的直接神经支配，并分析了投射到BST的各脑区中投射神经元的分布差异，在单细胞水平上研究了厌恶刺激对树鼩mPFC及其投射脑区中神经元编码模式的影响。（3）吗啡能显著增加树鼩的自发活动：吗啡作为树鼩愉悦刺激因子，腹腔注射吗啡后，实时观察记录树鼩活动，我们发现，给药前，树鼩每日关灯后10分钟左右就停止活动，进入休息状态；而腹腔注射吗啡后，树鼩在关灯后会间歇式的自由活动，活动量不大；而第二次给药后，树鼩明显活动量增大，并持续1-2小时，说明吗啡增强了树鼩的活动量。但是接下来断药后，并没有发现树鼩在关灯后自由活动增加。以上结果说明树鼩对初次吗啡给药没有明显反应，但是再次给药后，反应增强了。这些发现提示我们树鼩可为药物成瘾及其生理机制研究提供新的动物模型。总之，本课题研究提供了详实的树鼩脑图谱，结果说明情绪刺激改变了树鼩mPFC及其投射环路的情绪编码模式，并对其自发活动产生持久的影响。