The role of octopamine receptor-expressing neurons in aggression.

描述（由申请人提供）： 提供空间。本研究的主要目的是了解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，对生存和繁殖很重要。生物胺章鱼胺（OA）及其脊椎动物对应物去甲肾上腺素在攻击性以及各种其他社会行为中发挥重要作用。然而，这些分子调节不同社会行为的神经回路尚未得到很好的表征。这项建议的目的是表征电路介导OA的影响，在遗传上听话的生物果蝇的攻击行为。作为对这个问题的一个突破，我将使用遗传工具来改变章鱼胺受体表达神经元在体内的神经元活性，以回答以下问题：表达章鱼胺受体2（Oa 2）的神经元的活性如何影响攻击行为？哪些特定的Oa 2神经元亚群负责攻击行为，不同的群体控制攻击行为的各个方面？这些Oa 2神经元回路是如何调节攻击性的？它们调节的神经通路是什么？我将解决这些问题与以下具体目标：目标1-失去的功能和获得的功能操纵章鱼胺受体信号。目的2 -章鱼胺受体神经元亚群的鉴定和表征。目的3 -表征单个Oa 2神经元及其突触后靶点的投射。与公共卫生的相关性：在人类中，不受控制的、持续的或断章取义的攻击行为对社会产生了深远的负面影响。异常的攻击行为也与许多流行的精神疾病有关，如抑郁症、创伤后应激障碍和酒精成瘾。在遗传上易于处理的模式生物中研究攻击行为将增加我们对神经系统控制复杂行为状态（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.