The central amygdala circuits in motivated behaviors

动机性行为中的杏仁核中枢回路 项目摘要 中央杏仁核（CeA）包含异质性细胞类型，具有生长抑素表达（SOM+）神经元 和蛋白激酶C-β-表达（PKC-β +）神经元是两个最大的且基本上不重叠的神经元 人口。以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-β + CeA神经元在恐惧学习和表达中的作用不同。但据 长期以来，人们认识到CeA不仅有助于由厌恶刺激驱动的行为，而且还有助于那些 受食欲刺激的驱使，产生焦虑状态。事实上，最近的研究表明， CeA神经元类型，如SOM+神经元，可以驱动食欲行为和焦虑加剧。 然而，SOM+以及PKC-β + CeA神经元如何参与不同的动机行为， 仍然知之甚少。弥合这一知识差距将对改善临床表现具有重要意义。 治疗，因为CeA功能障碍与情绪或动机相关的疾病有关，包括 焦虑症、抑郁症和药物成瘾。 我们将通过研究SOM+神经元和PKC-β +的体内反应特性来解决这个问题。 在奖励或惩罚驱动的行为期间，CeA中的神经元，并确定这些神经元如何 响应用于控制下游电路的功能，并因此控制行为。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。根据我们的初步结果，我们设计了一个 整合的方法，结合体内成像，纤维光度学，光遗传学，化学遗传学和新的 行为技术，以测试我们的假设在以下具体目标： 目标1。探讨SOM+ CeA神经元在动机行为中的作用。 目标2.探讨PKC-β + CeA神经元在动机行为中的作用。 目标3：确定CeA-BNST回路如何促进焦虑相关行为。

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.