Neural mechanisms of foraging decisions

项目摘要/摘要 了解大脑是如何根据嘈杂的感觉信息做出决定的是中心目标之一 但过去研究这一过程的努力受到三个挑战的阻碍：(1)动物 在复杂环境中做出决策，这些环境并不总是映射到简单化的二元决策任务 通常在实验室中使用；(2)决策受到缓慢变化的变量的影响，例如 很难在短期的实验中研究；(3)决策涉及一个由相互作用的大脑组成的大型网络 地区，每个地区都影响着许多其他地区，并受到许多其他地区的影响。拟议的研究解决了这些问题 开发复杂而自然的小鼠觅食任务同时解决三个问题及其应用 最近开发的神经生物学技术来记录和操纵多个大脑区域的神经活动 在很长的时间尺度上。长期目标是利用行为和神经生物学的这种结合 在自然主义的背景下理解决策的技巧。 这项拟议的研究调查了觅食决定由神经整合器驱动的假设。 类似于用于整合感官证据以进行感知判断的机制，并且需要 皮质和纹状体之间的双向通讯，这通常是孤立地研究的，但实际上必须 沟通以产生决策。同时的光遗传微扰和大规模记录将是 用来解剖内侧前额叶皮质(MPFC)和背内侧纹状体(Dms)之间的相互作用， 在皮层和纹状体的许多相互关联的区域中，最有可能对 高效觅食所需的整合过程。事实上，mPFC的初步录音显示， 时间奖励整合。具有同时神经元的时空精确光遗传微扰 录音将揭示这种计算的哪些方面发生在局部的mPFC和/或通过皮质纹状体 互动。最后，新的纵向电生理记录技术将回答环境 价值是觅食决策中的一个关键变量，它是在很长的时间尺度(天)内跟踪的。这个问题一直是 过去很难研究，因为在更长的时间尺度上跟踪相同的神经元存在技术挑战 而不是几个小时。总之，这些实验将推动该领域对如何分布的理解 大脑区域网络解决了一个复杂但与行为相关的决策问题。这将创建 更深入地了解健康的大脑如何跟踪有益的结果以做出决策，这对 了解成瘾、强迫症和情绪等功能障碍状态下的问题 精神错乱。 该项目将在内田实验室的分子和细胞生物学系进行，地点为 哈佛大学。实验室和部门有充足的设备支持拟议的研究和 为奖学金申请者提供严格的博士后培训。

PROJECT SUMMARY / ABSTRACT Understanding how the brain makes decisions based on noisy sensory information is one of the central goals of neuroscience, but past efforts to study this process have been hindered by three challenges: (1) Animals make decisions in complex environments that do not always map onto the simplistic binary decision tasks typically used in the lab; (2) Decisions are influenced by slowly changing variables like environment value that are difficult to study in short experiments; (3) Decision making involves a large network of interacting brain regions, each of which influences and is influenced by many others. The proposed research addresses these three problems simultaneously by developing a complex yet naturalistic foraging task for mice and applying recently developed neurobiological techniques to record and manipulate neural activity in multiple brain regions over long time scales. The long-term objective is to use this combination of behavioral and neurobiological techniques to understand decision making in a naturalistic foraging context. The proposed research investigates the hypothesis that foraging decisions are driven by neural integrator mechanisms akin to those used to integrate sensory evidence for perceptual judgments, and require bidirectional communication between cortex and striatum, which are often studied in isolation but in fact must communicate to generate decisions. Simultaneous optogenetic perturbations and large-scale recordings will be used to dissect the interplay between medial prefrontal cortex (mPFC) and dorsomedial striatum (DMS), which of the many interconnected regions of cortex and striatum are among the most likely to contribute to the integration processes needed to forage efficiently. Indeed, preliminary mPFC recordings show signatures of temporal reward integration. Spatiotemporally precise optogenetic perturbations with simultaneous neural recordings will reveal which aspects of this computation occur locally in mPFC and/or through corticostriatal interactions. Finally, novel longitudinal electrophysiological recording techniques will answer how environment value, a key variable in foraging decisions, is tracked over long time scales (days). This question has been difficult to study in the past due to the technical challenge of tracking the same neurons over time scales longer than several hours. Together, these experiments will advance the field’s understanding of how distributed networks of brain areas solve a complex yet ethologically relevant decision-making problem. This will create deeper knowledge of how the healthy brain tracks rewarding outcomes to make decisions, which is critical for understanding what goes awry in dysfunctional states like addiction, obsessive compulsive disorder, and mood disorders. This project will take place in the Uchida Laboratory in the Department of Molecular and Cellular Biology at Harvard University. The Laboratory and Department are well-equipped to support the proposed research and provide rigorous postdoctoral training to the fellowship applicant.