Neural mechanisms of foraging decisions

项目总结/摘要 了解大脑如何根据嘈杂的感官信息做出决定是中心目标之一 但是过去研究这一过程的努力受到三个挑战的阻碍：（1）动物 在复杂的环境中做出决策，这些决策并不总是映射到简单的二元决策任务上 通常在实验室中使用;（2）决策受到缓慢变化的变量（如环境值）的影响， 很难在短期实验中研究;（3）决策涉及一个大型的相互作用的大脑网络 每个地区都影响着其他地区，也受到其他地区的影响。拟议的研究解决这些问题 三个问题，同时通过开发一个复杂的，但自然觅食任务的小鼠和应用 最近开发的神经生物学技术可以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。长期目标是使用这种行为和神经生物学的结合 技术来理解自然觅食背景下的决策。 该研究探讨了觅食决策是由神经整合驱动的假设 机制类似于那些用于整合感官证据的感知判断，并需要 皮质和纹状体之间的双向通信，这往往是孤立的研究，但实际上必须 沟通以做出决定。同时进行的光遗传学扰动和大规模记录将是 用于解剖内侧前额叶皮层（mPFC）和背内侧纹状体（DMS）之间的相互作用， 在许多相互连接的皮层和纹状体区域中， 整合过程需要有效地觅食。事实上，初步的mPFC记录显示， 时间报酬整合时空精确的光遗传学扰动与同时的神经 记录将揭示这种计算的哪些方面发生在mPFC局部和/或通过皮质纹状体 交互.最后，新颖的纵向电生理记录技术将回答环境如何 价值是觅食决策中的一个关键变量，在长时间尺度（天）上进行跟踪。这个问题已经 由于在更长的时间尺度上跟踪相同的神经元的技术挑战， 超过几个小时。总之，这些实验将促进该领域对如何分布 大脑区域的网络解决了一个复杂但与行为学相关的决策问题。这将创建 更深入地了解健康的大脑如何跟踪有益的结果来做出决定，这对 了解在成瘾、强迫症和情绪等功能失调状态下出现的问题 紊乱 该项目将在分子和细胞生物学系的内田实验室进行， 哈佛大学。实验室和部门设备齐全，以支持拟议的研究， 为奖学金申请人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.