Investigating Octopaminergic Neural Circuitry in Olfactory Appetitive Memory

描述（由申请人提供）：研究与公共卫生的相关性神经科学的一个重要目标是识别编码记忆和指导行为的神经回路。果蝇是研究记忆的神经基础的理想模式生物，因为它们可以被教导将条件刺激（气味）与显著的非条件刺激（蔗糖奖励）配对，并分析学习的关联。此外，果蝇的遗传学和进化技术允许对神经回路进行精确的时间和空间操作。该建议的重点是单胺，章鱼胺，昆虫的功能相当于哺乳动物的去甲肾上腺素及其在食欲记忆中的特定作用。主要目标是证明章鱼胺能神经元是否发出指示性非条件刺激信号，并且在CS-US关联时是必需的，或者它们是否参与动物的饥饿驱动导致CS-US关联。此外，该提案旨在确定与记忆相关的章鱼胺受体及其在苍蝇大脑中的作用位置。有几种人类疾病状态，包括情感障碍和成瘾，其中患者失去食欲控制，导致强迫行为。这项研究旨在研究编码食欲记忆的大脑系统如何整合传递条件和非条件刺激的神经网络，并将有助于理解人类食欲困扰背后的机械特性。

DESCRIPTION (provided by applicant): RELEVANCE OF RESEARCH TO PUBLIC HEALTH A vital objective of neural science is to identify the neural circuits that encode memory and guide behavior. Drosophila is an ideal model organism to study the neural basis of memory because they can be taught to pair a conditioned stimulus (odor) with a salient unconditioned stimulus (sucrose reward) and assayed for the learned association. Furthermore, the genetics and evolving technologies available in Drosophila allow for precise temporal and spatial manipulation of neural circuits. This proposal focuses on the monoamine, octopamine, the insect functional equivalent of mammalian noradrenaline and its specific role in appetitive memory. The primary goal is to demonstrate whether octopaminergic neurons signal the instructive unconditioned stimulus and are required at the time of CS-US association, or if they are instead involved in the animal's hunger drive leading up to the CS-US association. In addition, this proposal seeks to identify the memory-relevant octopamine receptors and their location of action in the fly brain. There are several human disease-states, including affective disorders and addiction, where patients lose appetitive control leading to compulsive behavior. The research proposed in this grant aims to investigate how the brain systems encoding appetitive memory integrate the neural networks conveying the conditioned and unconditioned stimuli and will help understand the mechanistic properties behind human appetitive afflictions.