Dopaminergic circuit modulation of learning and arousal-mediated memory enhancement

项目摘要 学习和记忆是由多巴胺能回路调节的，多巴胺能回路传递效价和/或唤醒信号。 这项建议将研究如何离散多巴胺能电路调节学习和记忆以及神经元 果蝇大脑记忆编码区域的可塑性。具体来说，它将理清以下角色： 多巴胺能回路传递正价信号、负价信号和非价依赖性信号， 唤醒信号体内成像实验将研究这些多巴胺能神经元如何驱动离散的 蘑菇体和下游的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 破译这些神经元亚群中的每一个如何调节唤醒、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通量来开发一种更有效的方法。 全面了解学习和记忆如何改变大脑中的信息流， 最终参与新颖的行为（例如，条件接近/回避）。 了解记忆是如何在大脑中编码的，以及在大脑疾病中是如何被破坏的， 记忆障碍治疗的合理设计。目前的研究结果将为以下方面提供指导 未来的研究将在多种模式生物中进行记忆形成的分子生物学研究， 多巴胺能回路调节跨分类群的唤醒和记忆。该项目将支持我们的长期目标， 了解记忆下降到单细胞和亚细胞水平，有助于知识库 这是合理开发记忆障碍新疗法所必需的。

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.