Dopaminergic circuit modulation of learning and arousal-mediated memory enhancement

学习的多巴胺能回路调节和唤醒介导的记忆增强

基本信息

批准号：
10217273
负责人：
Seth M Tomchik
金额：
$ 30.16万
依托单位：
SCRIPPS FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2022-04-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10217273
关键词：
Anatomy Animal Model Arousal Axon Behavior Behavioral Brain Brain Diseases Brain region Cells Code Complex Cues Cyclic AMP Data Desire for food Development Drosophila genus Drosophila melanogaster Genetic Goals Image Individual Learning Mediating Memory Memory Disorders Memory impairment Molecular Biology Mushroom Bodies Negative Valence Nervous system structure Neuronal Plasticity Neurons Odors Output Pattern Positive Valence Process Property Resolution Rewards Role Route Sensory Signal Transduction Stimulus Synapses Testing Work approach avoidance behavior classical conditioning dopaminergic neuron experimental study fly genetic manipulation in vivo in vivo imaging knowledge base memory encoding nervous system disorder neuronal circuitry neuroregulation neurotransmitter release novel optogenetics reinforcer response sensory stimulus therapy design tool

项目摘要

Project Summary Learning and memory are modulated by dopaminergic circuits, which convey valence and/or arousal signals. This proposal will examine how discrete dopaminergic circuits modulate learning and memory and neuronal plasticity in memory-encoding brain regions in Drosophila. Specifically, it will disentangle the roles of dopaminergic circuits that convey positive valence signals, negative valence signals, and valence-independent arousal signals. In vivo imaging experiments will examine how these dopaminergic neurons drive discrete patterns of plasticity in the mushroom body and downstream valence-coding output neurons that mediate approach and avoidance behavior. Complementary behavioral and optogenetic manipulation experiments will decipher how each of these neuronal subsets modulates arousal, valence, and memory strength. These studies will apply the large genetic toolkit and experimental throughput of the fly toward developing a more comprehensive understanding of how learning and memory alter the flow of information through the brain, to ultimately engage novel behaviors (e.g., conditioned approach/avoidance) following learning. Understanding how memories are encoded in the brain and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Results of the present studies will provide guideposts for future research into the molecular biology of memory formation across multiple model organisms, as dopaminergic circuits regulate arousal and memory across taxa. The project will support our long-term goal of understanding of memory down to the single-cell and subcellular levels, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.

项目概要学习和记忆由多巴胺能电路调节，多巴胺能电路传递效价和/或唤醒信号。该提案将研究离散的多巴胺能回路如何调节学习和记忆以及神经元果蝇记忆编码大脑区域的可塑性。具体来说，它将分解以下角色：传递正价信号、负价信号和价无关信号的多巴胺能电路唤醒信号。体内成像实验将检查这些多巴胺能神经元如何驱动离散的蘑菇体和下游价编码输出神经元的可塑性模式接近和回避行为。互补的行为和光遗传学操纵实验将破译这些神经元子集如何调节觉醒、效价和记忆强度。这些研究将应用大型遗传工具包和果蝇的实验吞吐量来开发更多全面了解学习和记忆如何改变大脑中的信息流，最终在学习后采取新的行为（例如，条件性接近/回避）。了解记忆如何在大脑中编码以及如何在大脑疾病中被破坏是了解记忆的先决条件。合理设计记忆障碍的治疗方法。目前的研究结果将为未来对跨多种模式生物体记忆形成的分子生物学的研究，如多巴胺能回路调节跨类群的唤醒和记忆。该项目将支持我们的长期目标对记忆的理解深入到单细胞和亚细胞水平，为知识库做出贡献对于合理开发记忆障碍的新疗法是必要的。