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.

修改后的项目摘要/摘要部分 该项目将从指导阶段机构(MIT)转移到R00机构(罗格斯大学-新不伦瑞克)。用适当的运动动作对来自环境的感觉信息作出反应需要至少两种不同的认知能力。注意投入优先处理与行为相关的感觉刺激，而运动规划允许从一系列可能的动作中选择适当的动作。虽然PFC被广泛用于指导注意力和运动规划，但目前还不清楚这些功能背后是相同的还是不同的神经底物。根据“运动前注意力理论”，注意力是执行行动的网络的一种突现属性，因此，同一组神经元对注意力和运动规划都有贡献。然而，最近的证据表明，这些功能是由不同类型的细胞提供的。在这个应用中，我将检验这样一个假设，即不同类型的PFC细胞分别以视觉皮质或上丘为靶点，上丘是协调运动行为的中脑结构，分别指导感觉处理或运动规划的注意力调节。在目标1中，我将使用光遗传失活来测试视觉皮质、上丘或PFC在一项新的双选择视觉任务中的作用，该任务具有特定的时间段，用于注意力参与或运动规划。(目标2a)接下来，我将使用投射特异性的光遗传失活来测试这一假设，即投射到视觉皮质的PFC细胞类型有助于视觉刺激的注意处理，而投射到上丘的细胞有助于运动规划。(目标2b)使用双光子显微镜，我将测量这两种细胞中注意力投入和运动规划的神经信号。(目标3a)在奖项的独立阶段，我将使用双突触解剖追踪策略来检验这样一种假设，即PFC输出到视觉皮质或上丘的不同功能来自于这些投射神经元群体接收的不同的突触前输入。使用轴突钙成像和计算分析，我将评估注意投入和运动规划在PFC输入的任务反应中的表征。(目标3b)平行地，我将使用光遗传失活来测试输入对两个PFC投射神经元的任务变量编码的功能贡献。总而言之，这些研究将确定远程输入和局部微电路之间的相互作用如何在特定的PFC细胞类型中产生任务相关变量的神经编码。我的长期职业目标是利用光学生理学的尖端技术了解小鼠认知功能的神经回路基础。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、功能双光子显微镜和基于病毒的电路跟踪。在这个奖项的指导阶段，我接受了行为任务设计、特定于投影的光遗传操作和数据分析计算方法的额外培训。这使我拥有了必要的工具来探索认知功能的神经基础，并开始我的独立研究生涯。