Prefrontal circuits for attention and motor planning

修改项目摘要/摘要部分 该项目将从指导阶段机构（麻省理工学院）转移到R 00机构（罗格斯大学-新玩法）。用适当的运动动作对来自环境的感官信息做出反应需要至少两种不同的认知能力。虽然注意力参与优先处理与行为相关的感官刺激，但运动规划允许从可能的运动曲目中选择适当的动作。虽然前额叶皮层在引导注意力和运动规划方面有着广泛的联系，但目前还不清楚这些功能背后是否有相同或不同的神经基质。根据“注意力的前运动理论”，注意力是执行动作的网络的一种涌现特性，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，这些功能由不同的细胞类型提供。在这个应用程序中，我将测试的假设，不同的PFC细胞类型的目标要么视觉皮层或上级丘，中脑结构，协调运动行为，指导注意力调节的感觉处理或运动规划，分别。在目标1中，我将使用光遗传失活来测试视觉皮层，上级丘，或PFC的性能上的一种新的两个选择的视觉任务与特定的时间段的注意力参与或运动规划的贡献。(Aim 2a）接下来，我将使用投射特异性光遗传学失活来检验这一假设，即投射到视觉皮层的PFC细胞类型有助于视觉刺激的注意处理，而投射到上级丘的细胞有助于运动规划。(Aim 2b）使用双光子显微镜，我将测量这两种细胞类型中注意参与和运动规划的神经特征。(Aim 3a）在本研究的独立阶段，我将使用双突触解剖追踪策略来检验这一假设，即PFC输出到视皮层或上级丘的差异功能来自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，我将评估的代表性的注意力参与和运动规划的任务响应的输入PFC。（目标3B）在平行的，我将使用光遗传失活测试的功能贡献的输入编码的任务变量的两个PFC投射神经元。总之，这些研究将建立远程输入和局部微电路之间的相互作用如何产生特定PFC细胞类型中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来了解小鼠认知功能的神经回路基础。为了实现这一目标，我接受了各种技术的培训，包括细胞神经生理学，功能性双光子显微镜和基于病毒的电路跟踪。在该奖项的指导阶段，我接受了行为任务设计，特定投影光遗传学操作和数据分析计算方法的额外培训。这为我提供了必要的工具来探索认知功能的神经基础，并开始了我的独立研究生涯。

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.