The central amygdala circuits in motivated behaviors

动机行为中的中央杏仁核环路 项目摘要 中央杏仁核(CEA)含有不同类型的细胞，有生长抑素表达(SOM+)神经元 和蛋白激酶C-表达(PKC-+)神经元是两个最大且基本上不重叠的神经元 人口。此前的研究主要集中在这些神经元在恐惧条件反射中的作用，揭示了 SOM+和PKC-+CEA神经元对恐惧的学习和表达有不同的贡献。然而，它是 Long认识到，CEA不仅对厌恶刺激驱动的行为有贡献，而且对 在食欲刺激的驱使下，产生焦虑状态。事实上，最近的研究表明， 不同类型的CEA神经元，如SOM+神经元，可以驱动食欲行为和加剧焦虑。 然而，SOM+和PKC-+CEA神经元如何参与不同的动机行为 人们对此仍然知之甚少。弥合这一知识鸿沟将对改善 治疗，因为CEA功能障碍与情绪或动机相关的障碍有关，包括 焦虑症、抑郁症和毒瘾。 我们将通过研究SOM+神经元和PKC-+的体内反应特性来解决这个问题 在奖赏或惩罚驱动的行为过程中，CEA中的神经元，并决定这些 响应用于控制下游电路的功能，从而控制行为。我们的中央 假设CEA神经元影响奖赏寻求和惩罚回避的学习或表达 通过它们对不同目标的远程投射。基于我们的初步结果，我们设计了一种 结合活体成像、纤维光度学、光遗传学、化学遗传学和新技术的综合方法 行为技术，以检验我们的假设在以下具体目标： 目的1.确定SOM+CEA神经元在动机行为中的作用。 目的2.探讨PKC-+CEA神经元在动机行为中的作用。 目的3.确定CEA-BNST回路对焦虑相关行为的影响。

The central amygdala circuits in motivated behaviors Project Summary The central amygdala (CeA) contains heterogeneous cell types, with somatostatin-expressing (SOM+) neurons and protein kinase C--expressing (PKC-+) neurons being two largest and largely non-overlapping populations. Previous studies have mainly focused on the roles of these neurons in fear conditioning, revealing that SOM+ and PKC-+ CeA neurons differentially contribute to fear learning and expression. However, it is long recognized that the CeA contributes not only to behaviors driven by aversive stimuli, but also to those driven by appetitive stimuli, and to the generation of anxiety state. Indeed, recent studies show that distinct types of CeA neurons, such as SOM+ neurons, can drive appetitive behaviors and heightened anxiety. However, how the SOM+ as well as PKC-+ CeA neurons participate in divergent motivational behaviors remains poorly understood. Bridging this knowledge gap will have important clinical implications for improved treatments, as CeA dysfunctions have been implicated in mood- or motivation-related disorders, including anxiety disorders, depression and drug addiction. We will address this question by investigating the in vivo response properties of SOM+ neurons and PKC-+ neurons in the CeA during behaviors driven by either reward or punishment, and determining how these responses are used to control the functions of downstream circuits and, hence, behavior. Our central hypothesis is that CeA neurons influence learning or expression of reward seeking and punishment avoidance through their long-range projections to different targets. Based on our preliminary results, we devised an integrated approach, combining in vivo imaging, fiber photometry, optogenetics, chemogenetics and novel behavioral techniques, to test our hypotheses in the following Specific Aims: Aim 1. To determine the roles of SOM+ CeA neurons in motivational behaviors. Aim 2. To determine the roles of PKC-+ CeA neurons in motivational behaviors. Aim 3. To determine how a CeA-BNST circuit contributes to anxiety-related behaviors.