Dopaminergic regulation of spatial learning

空间学习的多巴胺能调节

• 批准号: 10709022
• 负责人: Rachel Wilson
• 金额: $ 41.25万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709022
• 关键词: Acceleration; Anatomy; Back; Behavior; Brain; Calcium; Calibration; Cells; Cognition; Complex; Computer Models; Cues; Defect; Dopamine; Dopaminergic Cell; Drosophila genus; Electrophysiology (science); Environmental Wind; Feedback; Genetic; Head; Image; Learning; Link; Locomotion; Maps; Memory; Monitor; Movement; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Organism; Positioning Attribute; Regulation; Rewards; Role; Sensory; Signal Transduction; Speed; Synapses; Synaptic plasticity; System; Testing; Time; Visual; Weight; Whole-Cell Recordings; cell type; clinically relevant; cognitive process; connectome; design; discount; dopaminergic neuron; experimental study; fly; in silico; in vivo; in vivo calcium imaging; model organism; neural network; neuromechanism; response; theories; virtual reality environment; way finding

Summary In neural networks that store information in their connection weights, there is a tradeoff between sensitivity and stability. Connections must be plastic to incorporate new information, but if they are too plastic, stored information can be corrupted. Therefore, it would be useful if learning rates in the brain were regulated by a “when-to-learn” signal that varies with the current availability of new information. In reward learning, dopamine is known to serve this function, by rapidly upregulate synaptic plasticity in response to reward prediction errors. The overarching hypothesis of this proposal is that dopamine also provides a when-to-learn signal for spatial learning. During spatial learning, new information is generally available when an organism is moving through space. Thus, we hypothesize that spatial learning is modulated by dopamine release that is specifically linked to active movements. This idea is attractive because it can provide an explanation for why so many dopamine neurons are time-locked to movements. This proposal outlines three projects, all focusing on spatial learning in the central complex, the primary center for spatial navigation in the Drosophila brain. In each project, there is anatomical evidence from the Drosophila connectome that implies a role for dopamine neurons. Moreover, in each project, there is already evidence that the dopamine neurons in question are active when the fly is locomoting. This motivates our hypothesis that dopamine links movement to spatial learning. Although these projects are linked conceptually, they each focus on a distinct dopamine cell type, and a distinct form of spatial learning. First, we will determine how dopamine modulates learning about spatial position cues in the head direction system. Second, we will investigate the hypothesis that dopamine modulates learning about rotational velocity cues in the head direction system. Third, we will investigate the hypothesis that a feedback circuit integrates information over time to discount the influence of environmental wind shifts on head direction neurons. In all three projects, we use connectome analyses and computational modeling to generate testable predictions about specific networks in the brain. Then, we test these predictions using in vivo calcium imaging and/or electrophysiology as flies navigate in virtual reality environments. Our results should shed light on the fundamental mechanisms underlying navigation behaviors in all complex species, including ring attractor networks, Hebbian learning rules, and feedback loops. Broadly speaking, we think that dopamine provides a control knob for modulating these mechanisms up or down. As such, we see dopaminergic neurons as an entry point for an integrative understanding of network dynamics during complex cognitive processes.

总结 在将信息存储在其连接权重中的神经网络中， 与稳定连接必须是塑料的，以纳入新的信息，但如果他们太塑料，存储 信息可能被破坏。因此，如果大脑中的学习率是由一种 “何时学习”信号随新信息的当前可用性而变化。在奖励学习中， 已知多巴胺通过快速上调突触可塑性来对奖赏做出反应，从而发挥这种功能 预测误差。这个提议的首要假设是，多巴胺也提供了一个何时学习的机制， 空间学习的信号在空间学习过程中，新信息通常是可用的， 在太空中移动因此，我们假设空间学习是由多巴胺释放调节的， 特别是与主动运动有关的。这个想法很吸引人，因为它可以解释为什么会这样。 许多多巴胺神经元对运动是时间锁定的。该提案概述了三个项目，所有这些项目都侧重于 空间学习在中央复合体，空间导航在果蝇大脑的主要中心。在 每一个项目，都有来自果蝇连接体的解剖学证据，暗示多巴胺的作用， 神经元此外，在每个项目中，已经有证据表明，有问题的多巴胺神经元是活跃的 当苍蝇飞向空中时。这激发了我们的假设，即多巴胺将运动与空间学习联系起来。 虽然这些项目在概念上是联系在一起的，但它们各自专注于一种不同的多巴胺细胞类型， 空间学习的形式。首先，我们将确定多巴胺如何调节空间位置线索的学习 在头部方向系统中。其次，我们将研究多巴胺调节学习的假设 关于头部方向系统中的旋转速度线索。第三，我们将研究一个假设， 反馈电路随时间整合信息，以减少环境风变化对 头部方向神经元在这三个项目中，我们使用连接体分析和计算建模， 对大脑中的特定网络产生可测试的预测。然后，我们使用体内试验来测试这些预测。 钙成像和/或电生理学。我们的结果应该 阐明了所有复杂物种导航行为的基本机制，包括 环吸引子网络，赫布学习规则和反馈回路。一般来说，我们认为多巴胺 提供了一个控制旋钮，用于向上或向下调节这些机构。因此，我们看到多巴胺能神经元 作为一个切入点，在复杂的认知过程中的网络动态的综合理解。