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 该项目将获得R00的指导阶段工厂（MIT）（新的不伦瑞克省）。可能的运动曲目在指导和运动计划方面尚不清楚，目前尚不清楚与运动和运动计划相同的神经底层。在此应用程序中，我将测试带有运动行为的车间，以指导感官处理或运动计划的态度。视觉皮层，上胶或PFC的性能，具有特定的颞时期，以进行Attental参与或运动计划。在这两种细胞类型中，较高的罪行进行了运动范围。这些刺激成像和计算分析所接受的前naputs，我将评估Attensional Contagention和Motor Planning在任务响应中（AIM 3B，我将使用光遗传学乌龙。这些研究通过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的变量的神经编码。使用Tting-Edge技术来促进这一目标，我接受了各种技术的培训，包括细胞神经理学，功能性的两光子显微镜和病毒 - 低 - 低音的回路。特定的光遗传操作和数据计算方法为我提供了探测认知功能的神经基础所需的工具并启动了我的独立研究职业。