The Role of the Midbrain Reticular Nucleus in Vision and Perceptual Decision-Making

项目摘要：视觉处理和知觉决策方面的障碍是导致 阿尔茨海默病和精神分裂症等神经精神障碍的发病率。这样做的主要目标是 训练方案是在视觉感知的基础上刻画分布式网络中潜在的新节点 决策--中脑网状核(MRN)。感性决策的经典模型归因于 前脑感觉运动区的决策形成，中脑存在于前馈的末端 传递运动指令的路径。然而，有大量证据表明，中脑，特别是 上丘(SC)参与视觉决策过程。此外，我们最近的研究表明， 各种各样的编码，从动作到动作选择，甚至到抽象的认知表征，如线索 估值，同时分布在整个大脑的多个区域。我们假设这个编码 该方案也适用于视觉决策，包括MRN和SC在内的中脑区域参与了 与大脑皮层和基底节的区域形成网络以形成决策。 传统上，MRN被认为是一个纯粹与电机相关的区域。挑战这一观念，我们 最近在一项视觉决策任务中在MRN中发现了视觉和动作选择信号。问题仍然存在 然而，关于MRN中的不同编码是如何在拓扑上组织的，视觉反应是否 任务学习的结果，MRN中抽象决策信号的编码，以及MRN如何与 更广泛的感知决策电路。本培训方案通过以下方式逐一解决这些问题 利用NeuroPixels 2.0探头的规模和我设计的一个新颖的视觉反向应急任务 用于区分感觉、运动和决策信号。Aim 1A使用NeuroPixels 2.0录音 通过观察各种刺激的小鼠的MRN来构建感觉和运动编码的地形图，以及 目标1B在被动感知任务刺激的任务幼稚和训练的小鼠中使用类似的记录来评估视觉 MRN中的可塑性。Aim 2A在任务执行期间使用跨MRN的录音来确定 抽象决策信号，Aim 2B在整个视觉决策网络中使用多探头记录来 在决策形成过程中建立区域间的互动。这些目标加在一起将增进我们的理解 以及产生可视化决策的复杂计算，从而 提高我们在这个过程出错的地方精确定位关键电路的能力。 在我量身定做的训练期间，我将学习神经像素电生理学、啮齿动物行为任务 设计和实施、全脑组织处理和成像以及高级计算 在支持性培训环境中，在专家指导下的分析技术。这些技能加在一起 在世界领先的医疗机构接受临床培训，这将使我为独立的职业生涯做好理想的准备 内科医生-科学家，致力于促进对神经系统疾病的理解和治疗。

Project Summary: Impairments in visual processing and perceptual decision-making are a significant cause of morbidity in neuropsychiatric disorders such as Alzheimer’s disease and schizophrenia. The primary goal of this training proposal is to characterize a potentially novel node in the distributed network underlying visual perceptual decision-making - the midbrain reticular nucleus (MRN). Classical models of perceptual decision-making ascribe decision formation to forebrain sensorimotor regions, with the midbrain existing at the end of a feedforward pathway to relay motor commands. However, there is substantial evidence that the midbrain, especially the superior colliculus (SC), participates in the visual decision process. Additionally, our recent work has shown that a variety of coding, from movements, to action selection, to even abstract cognitive representations such as cue valuation, is simultaneously distributed in multiple regions throughout the brain. We hypothesize that this coding scheme applies to visual decisions as well, with midbrain regions including MRN and SC participating in a network with regions in the cortex and basal ganglia to form the decision. The MRN has traditionally been thought of as a purely motor-related region. Challenging this notion, we recently found visual and action selection signals in MRN during a visual decision-making task. Questions remain however regarding how the diverse coding in MRN is organized topographically, whether visual responses are a result of task learning, the encoding of abstract decision signals in MRN, and how MRN interacts with the broader perceptual decision-making circuitry. This training proposal addresses each of these questions by leveraging the scale of Neuropixels 2.0 probes and a novel visual reverse contingency task I have designed and implemented to distinguish sensory, motor, and decision signals. Aim 1A uses Neuropixels 2.0 recordings across MRN in mice viewing a variety of stimuli to build a topographic map of sensory and motor coding, and Aim 1B uses similar recordings in task-naive and trained mice passively perceiving task stimuli to assess visual plasticity in MRN. Aim 2A uses recordings across MRN during task performance to establish the presence of abstract decision signals, and Aim 2B uses multi-probe recordings throughout the visual decision network to establish inter-area interactions during decision formation. Together these aims will advance our understanding of the distributed regions and the complex computations that give rise to visual decision-making, thereby improving our ability to precisely target key circuits in disorders where this process goes awry. During my tailored training period, I will learn Neuropixels electrophysiology, rodent behavioral task design and implementation, whole-brain histological processing and imaging, and advanced computational analysis techniques under the guidance of experts in a supportive training environment. These skills, combined with clinical training in a world-leading medical institution, will ideally prepare me for an independent career as a physician-scientist working to advance the understanding and treatment of neurological disorders.