Prefrontal circuits for attention and motor planning

用于注意力和运动规划的前额叶回路

• 批准号: 10368139
• 负责人: Rafiq Huda
• 金额: $ 24.47万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368139
• 关键词: Address; Aging; Anatomy; Animals; Apraxias; Area; Attention; Attention deficit hyperactivity disorder; Attentional deficit; Award; Axon; Behavior; Behavioral; Brain; Brain region; Calcium; Cells; Code; Color; Computer Analysis; Computing Methodologies; Cues; Data Analyses; Disease; Environment; Goals; Handedness; Head; Human; Hypersensitivity; Image; Institution; Measures; Mentors; Midbrain structure; Motor; Movement; Mus; Nervous System Trauma; Neurons; New Brunswick; Optics; Output; Pathway interactions; Performance; Phase; Physiology; Population; Prefrontal Cortex; Property; Research; Role; Sensory; Source; Specific qualifier value; Stimulus; Structure; System; Task Performances; Techniques; Testing; Therapeutic Intervention; Tracer; Training; Universities; Viral; Visual; Visual Cortex; anatomical tracing; attentional modulation; base; career; cell type; cognitive ability; cognitive function; cognitive neuroscience; design; experimental study; motor behavior; neural circuit; neural correlate; neural network; neuromechanism; neurophysiology; new therapeutic target; novel; optogenetics; presynaptic; relating to nervous system; response; sensory stimulus; signal processing; stimulus processing; superior colliculus Corpora quadrigemina; theories; tool; two photon microscopy; two-photon; visual motor; visual processing; visual stimulus

Modified Project Summary/Abstract Section This project will be moved from the mentored phase institution (MIT) to the R00 institution (Rutgers University – New Brunswick). Responding to sensory information from the environment with appropriate motor actions requires at least two distinct cognitive abilities. While attentional engagement prioritizes behaviorally relevant sensory stimuli for processing, motor planning allows for selection of appropriate actions from a repertoire of possible movements. While the PFC has been widely implicated in guiding attention and motor planning, it is unclear if the same or distinct neural substrates underlie these functions. According to the ‘pre-motor theory of attention’, attention is an emergent property of networks that implement actions and, hence, the same set of neurons contribute to both attention and motor planning. However, recent evidence suggests that these functions are served by distinct cell types. In this application, I will test the hypothesis that distinct PFC cell-types target either the visual cortex or superior colliculus, a midbrain structure that coordinates motor behavior, to guide attentional modulation of sensory processing or motor planning, respectively. In Aim 1, I will use optogenetic inactivation to test the contribution of visual cortex, superior colliculus, or PFC to performance on a novel two-choice visual task with specific temporal epochs for attentional engagement or motor planning. (Aim 2a) Next, I will use projection-specific optogenetic inactivation to test the hypothesis that PFC cell-types that project to visual cortex contribute to attentional processing of visual stimuli, whereas cells projecting to superior colliculus contribute to motor planning. (Aim 2b) Using two-photon microscopy, I will measure the neural signatures of attentional engagement and motor planning in these two cell-types. (Aim 3a) In the independent phase of the award, I will use a disynaptic anatomical tracing strategy to test the hypothesis that the differential function of PFC outputs to the visual cortex or the superior colliculus arises from distinct set of presynaptic inputs received by these projection neuron populations. Using axonal calcium imaging and computational analyses, I will assess the representation of attentional engagement and motor planning in task responses of inputs to the PFC. (Aim 3b) In parallel, I will use optogenetic inactivation to test the functional contribution of inputs to coding of task variables by the two PFC projection neurons. Together, these studies will establish how interactions between long-range inputs and local microcircuits produce neural coding of task-related variables in specific PFC cell-types. My long-term career goal is to understand the neural circuit basis of cognitive function in mice using cutting-edge techniques for optical physiology. To facilitate this goal, I have received training in a variety of techniques including cellular neurophysiology, functional two-photon microscopy, and viral-based circuit tracing. During the mentored phase of this award, I received additional training in behavioral task design, projection-specific optogenetic manipulations, and computational methods for data analysis. This has equipped me with the tools necessary to probe the neural underpinnings of cognitive functions and launch my independent research career.

修改的项目摘要/摘要部分 该项目将从修订的阶段机构（MIT）转移到R00机构（Rutgers University - New Brunswick）。通过适当的运动动作响应来自环境的感官信息需要至少两个不同的认知能力。尽管注意力参与优先考虑行为相关的感觉刺激进行处理，但运动计划允许从可能的运动曲目中选择适当的动作。尽管PFC在指导注意力和运动计划方面已被广泛实施，但尚不清楚这些功能是相同或不同的神经元底物。根据“关注前运动理论”，注意是网络的紧急特性，该网络实施动作，因此相同的神经元既有助于注意力和运动计划。但是，最近的证据表明，这些功能由不同的细胞类型提供。在此应用程序中，我将测试以下假设：不同的PFC细胞类型靶向可视觉皮层或超级胶囊，这是一种协调运动行为的中脑结构，以指导感官处理或运动计划的注意力调制。在AIM 1中，我将使用光遗传学灭活来测试视觉皮层，超级胶囊或PFC对新型两项视觉任务的性能的贡献，该任务具有特定的临时时期，以进行注意力参与或运动计划。 （AIM 2A）接下来，我将使用投影特异性的光遗传学灭活来检验以下假设：将视觉皮质的PFC细胞类型投射到视觉刺激的注意力过程中，而投影到上层胶囊的细胞有助于运动计划。 （AIM 2B）使用两光子显微镜，我将在这两种细胞类型中测量注意力参与和运动计划的神经特征。 （AIM 3A）在奖励的独立阶段，我将使用双突触的解剖示踪策略来检验以下假设：PFC输出对视觉皮层的差异功能或Super Colliculus源于这些投射神经元种群收到的不同突触前输入集。使用轴突钙成像和计算分析，我将评估注意力参与和运动计划的表示，以对PFC的输入的任务响应。 （AIM 3B）并行，我将使用光遗传学失活来测试输入对两个PFC投影神经元对任务变量编码的功能贡献。总之，这些研究将确定长期输入和局部微电路之间的相互作用如何在特定的PFC细胞类型中产生与任务相关变量的神经元编码。我的长期职业目标是使用光学生理学的尖端技术了解小鼠认知功能的神经元电路基础。为了促进这一目标，我接受了各种技术的培训，包括细胞神经生理学，功能性两光子显微镜和基于病毒的电路跟踪。在该奖项的修改阶段，我接受了行为任务设计，特定于投影的光遗传操作以及用于数据分析的计算方法的额外培训。这已经为我提供了所需的工具来探究认知功能的神经元基础并启动我的独立研究生涯。