Dopaminergic regulation of spatial learning

空间学习的多巴胺能调节

基本信息

批准号：
10561863
负责人：
Rachel Wilson
金额：
$ 42.38万
依托单位：
HARVARD MEDICAL SCHOOL
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：
2022-09-22 至 2027-08-31
项目状态：
未结题

项目摘要

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.

概括在将信息存储在其连接权重的神经网络中，灵敏度之间有一个折衷和稳定性。连接必须是塑料才能包含新信息，但是如果它们太塑料，则存储信息可能会损坏。因此，如果大脑中的学习率受到A的调节，这将是有用的 “何时学习”信号随当前可用性而变化。在奖励学习中，众所周知，多巴胺可以通过快速上调突触可塑性来响应奖励来发挥这种功能预测错误。该提议的总体假设是多巴胺还提供了一条何时学习空间学习的信号。在空间学习期间，当生物体为穿过太空。这，我们假设空间学习是由多巴胺释放调节的专门链接到主动运动。这个想法很有吸引力，因为它可以说明为什么这样许多多巴胺神经元被滞留到运动中。该提案概述了三个项目，都关注中央综合体的空间学习是果蝇大脑空间导航的主要中心。在每个项目，都有果蝇连接组的解剖学证据，这意味着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活跃当苍蝇处于机车状态时。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。尽管这些项目在概念上是链接的，但它们每个都集中在独特的多巴胺细胞类型上，并且是独特的空间学习的形式。首先，我们将确定多巴胺如何调节有关空间位置提示的学习在头方向系统中。其次，我们将研究多巴胺调节学习的假设关于旋转速度提示在头方向系统中。第三，我们将研究以下假设反馈电路会随着时间的推移整合信息，以降低环境风的影响头部方向神经元。在所有三个项目中，我们都将Connectome分析和计算建模用于生成有关大脑特定网络的可测试预测。然后，我们使用体内测试这些预测钙成像和/或电生理学随着虚拟现实环境导航。我们的结果应该阐明了所有复杂物种中导航行为的基本机制，包括戒指吸引者网络，HEBBIAN学习规则和反馈循环。从广义上讲，我们认为多巴胺提供一个控制旋钮，以调节这些机制向上或向下调节。因此，我们看到多巴胺能神经元作为对复杂认知过程中网络动态的集成理解的入口点。