The central amygdala circuits in motivated behaviors

动机行为中的中央杏仁核回路

基本信息

批准号：
10319604
负责人：
Bo LI
金额：
$ 70.96万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10319604
关键词：
Address Amygdaloid structure Anxiety Anxiety Disorders Appetitive Behavior Area Aversive Stimulus Behavior Behavioral Brain Cell physiology Clinical Data Desire for food Disease Disinhibition Dopamine Drug Addiction Dynorphins Educational process of instructing Environment Fiber Fright Functional disorder Generations Genetic Markers Goals Human Impairment Knowledge Learning Measures Mental Depression Moods Motivation Mus Neurons Neuropeptides Pathway interactions Pharmaceutical Preparations Photometry Play Population Process Property Protein Kinase C Punishment Regulation Research Rewards Role Signal Transduction Somatostatin Stimulus Stress Structure Structure of terminal stria nuclei of preoptic region System Techniques Testing anxiety states anxiety-related behavior avoidance behavior base behavioral response cell type cholinergic conditioned fear improved in vivo in vivo imaging insight motivated behavior neuromechanism neuroregulation novel optogenetics programs response sensor

项目摘要

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.

动机行为中的中央杏仁核电路项目摘要中央杏仁核（CEA）包含异质细胞类型，表达生长抑素（SOM+）神经元和蛋白激酶表达（PKC-+）神经元是两个最大的，主要是非重叠的神经元人群。先前的研究主要集中在这些神经元在恐惧条件下的作用，从而揭示 SOM+和PKC-+ CEA神经元有助于恐惧学习和表达。但是，是长期以来，CEA不仅为厌恶刺激驱动的行为做出了贡献，而且对由食欲刺激和动画状态的产生驱动。确实，最近的研究表明，独特 CEA神经元（例如SOM+神经元）的类型可以驱动食欲和动画增强。但是，SOM+以及PKC-++ CEA神经元如何参与不同的动机行为仍然很了解。桥接此知识差距将具有重要的临床意义以改善治疗，如心情或动机有关的疾病，包括焦虑症，抑郁和吸毒。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行为中，CEA中的神经元是由奖励或惩罚驱动的，并确定这些响应用于控制下游电路的功能以及行为。我们的中心假设是CEA神经元会影响奖励寻求和惩罚的学习或表达通过他们的远程项目到不同的目标。根据我们的初步结果，我们设计了一个综合方法，结合体内成像，纤维光度法，光遗传学，化学遗传学和新型行为技术，以以下特定目的检验我们的假设：目的1。确定SOM+ CEA神经元在动机行为中的作用。目标2。确定PKC-+ CEA神经元在动机行为中的作用。目标3。确定CEA-BNST电路如何促进与焦虑相关的行为。