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：
10731978
负责人：
Seth M Tomchik
金额：
$ 36.54万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-11-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10731978
关键词：
Anatomy Arousal Association Learning Axon Behavior Behavioral Brain Brain Diseases Brain region Cells Code Complex Cues Cyclic AMP Data Dedications 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 Neuronal Plasticity Neurons Odors Output Pattern Positive Valence Process Property Resolution Rewards Role Route Sensory Signal Transduction Stimulus Synapses Testing Work approach behavior avoidance behavior dopaminergic neuron experimental study fly genetic manipulation in vivo in vivo imaging knowledge base memory encoding model organism nervous system disorder neuronal circuitry neuroregulation neurotransmitter release novel optogenetics rational design reinforcer response sensory stimulus therapy design tool

Anatomy Arousal Association Learning Axon Behavior Behavioral Brain Brain Diseases Brain region Cells Code Complex Cues Cyclic AMP Data Dedications 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 Neuronal Plasticity Neurons Odors Output Pattern Positive Valence Process Property Resolution Rewards Role Route Sensory Signal Transduction Stimulus Synapses Testing Work approach behavior avoidance behavior dopaminergic neuron experimental study fly genetic manipulation in vivo in vivo imaging knowledge base memory encoding model organism nervous system disorder neuronal circuitry neuroregulation neurotransmitter release novel optogenetics rational design reinforcer response sensory stimulus therapy design tool

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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.

项目摘要学习和记忆是由多巴胺能电路调节的，这些电路传达价和/或唤醒信号。该建议将检查离散多巴胺能电路如何调节学习和记忆和神经元果蝇中记忆编码大脑区域的可塑性。具体而言，它将解开传达正价信号，负价信号和价无关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蘑菇体和下游价值编码输出神经元中的可塑性模式方法和回避行为。互补的行为和光遗传操作实验将破译这些神经元子集如何调节唤醒，价和记忆力。这些研究将应用大型遗传工具包和苍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通过大脑的信息流，最终在学习后会涉及新颖的行为（例如，有条件的方法/避免）。了解记忆如何在大脑中编码并在脑部疾病中破坏是一种先决条件用于记忆障碍的治疗方法的理性设计。本研究的结果将为指南提供对多种模型生物的记忆形成的分子生物学的未来研究，多巴胺能电路调节整个分类单元的唤醒和记忆。该项目将支持我们的长期目标了解记忆至单细胞和亚细胞水平，有助于知识库对于记忆障碍的新型治疗方法的合理发展所必需的。