The role of octopamine receptor-expressing neurons in aggression.

描述(由申请人提供)： 所提供的空间。研究综述：本研究提案的主要目的是了解支配神经回路如何产生复杂行为的逻辑。我选择把重点放在攻击性上，这是一种几乎普遍的动物行为，对生存和繁殖非常重要。生物胺章鱼胺和其对应的脊椎动物去甲肾上腺素在攻击和其他各种社会行为中发挥着重要作用。然而，这些分子调节不同社会行为的神经回路还没有得到很好的描述。这项建议的目的是描述在遗传易驯化的生物黑腹果蝇中，调节OA对攻击行为影响的回路的特征。为了解决这个问题，我将使用遗传工具来改变体内表达章鱼胺受体的神经元的神经元活动，以回答以下问题：表达章鱼胺受体2(OA2)的神经元的活动如何影响攻击行为？负责攻击行为的Oa2神经元的特定亚群是什么，不同的群体是否控制着攻击行为的各个方面？这些Oa2神经元回路是如何起到调节攻击行为的作用的？它们调节的神经通路是什么？我将通过以下具体目标来解决这些问题：目标1-章鱼胺受体信号的功能丧失和功能获得操纵。目的2-章鱼胺受体神经元亚群的鉴定和鉴定。目的3-描述单个OA2神经元及其突触后靶点的投射特征。与公共健康相关：在人类中，不受控制、持续的或断章取义的攻击行为对社会有深远的负面影响。异常的攻击性行为还与许多普遍存在的精神障碍有关，如抑郁症、创伤后应激障碍和酒精成瘾。研究遗传上易驯化的模型生物中的攻击行为将增加我们对神经系统用来控制复杂行为状态(如攻击)的基本神经回路机制的理解。

DESCRIPTION (provided by applicant): SPACE PROVIDED. Research Summary: The major goal of this research proposal is to understand the logic that governs how neural circuits give rise to complex behaviors. I have chosen to focus on aggression, a nearly universal animal behavior that is important for survival and reproduction. The biogenic amine octopamine (OA), and its vertebrate counterpart noradrenalin, play important roles in aggression, as well as a variety of other social behaviors. However, the neural circuits on which these molecules act to regulate different social behaviors have not been well characterized. The aim of this proposal is to characterize the circuits that mediate the effects of OA on aggressive behavior in the genetically tractable organism Drosophila melanogaster. As an inroad to this problem, I will use genetic tools to alter neuronal activity of octopamine receptor-expressing neurons in vivo in order to answer the following questions: How does the activity of neurons expressing octopamine receptor 2 (Oa2) influence aggressive behaviors? What are the specific subpopulations of Oa2 neurons that are responsible for aggression and do different populations control various aspects of aggressive behavior? How do these Oa2 neuronal circuits function to mediate aggression and what are the neural pathways that they modulate? I will address these questions with the following specific aims: Aim 1- Loss-of-function and gain-of-function manipulations of octopamine receptor signaling. Aim 2 - Identification and characterization of octopamine receptor neuronal subsets. Aim 3 - Characterization of the projections of individual Oa2 neurons and their post-synaptic targets. Relevance to public health: In humans, aggression that is unchecked, persistent, or expressed out of context has profound negative impacts on society. Aberrant aggressive behavior is also associated with numerous prevalent psychiatric disorders such as depression, post-traumatic stress disorder and alcohol addiction. Investigating aggressive behavior in a genetically tractable model organism will increase our understanding of the basic neural-circuit mechanisms used by the nervous system to control complex behavioral states, such as aggression.