The Dynamics and Behavioral Role of Choice-Predictive Neurons in Sensory Cortex

感觉皮层选择预测神经元的动力学和行为作用

• 批准号: 10542660
• 负责人: Ravi Pancholi
• 金额: $ 2.56万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2023-05-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10542660
• 关键词: Ablation; Advanced Development; Affect; Afferent Neurons; Amputation; Amputees; Animals; Area; Behavior; Behavior assessment; Behavioral; Calcium; Cells; Data; Discrimination; Disease; Exhibits; Feedback; Image; Injury; Knowledge; Learning; Limb Prosthesis; Limb structure; Link; Monitor; Mus; Nervous System Trauma; Neurons; Noise; Opsin; Optics; Pathway interactions; Patients; Perception; Peripheral; Phantom Limb Pain; Physiologic pulse; Population; Probability; Process; Prosthesis; Quality of life; Reporting; Resolution; Role; Sensory; Series; Somatosensory Cortex; Spinal cord injury; Stable Populations; Stimulus; Stroke; Synapses; Task Performances; Technology; Testing; Training; Transgenic Animals; Transgenic Mice; Viral; behavior influence; brain machine interface; calcium indicator; design; experimental study; gain of function; hippocampal pyramidal neuron; imaging approach; improved; individual response; insight; learned behavior; loss of function; microstimulation; multi-photon; neural; neural prosthesis; optogenetics; photostimulus; sensory cortex; sensory feedback; sensory input; somatosensory; two-photon

PROJECT SUMMARY The loss of a functional limb due to amputation, stroke, or spinal cord injury has devastating consequences for quality of life. Brain-machine interfaces (BMIs) present a means to restore lost functionality by providing patients with voluntary control over a prosthetic limb. However, most such BMIs lack somatosensory feedback, which has severely limited their efficacy. A major reason somatosensory feedback remains absent from neural prostheses is that we have yet to understand the relationship between neural activity in sensory cortex and behavior. One approach to relating neural activity with behavior has been to study choice-related activity in sensory cortex. Choice-related activity is neural activity that can be used to predict animals’ behavioral choices and has been identified in numerous sensory areas as animals perform a variety of behavioral tasks. However, because of technological limitations, it remains unclear how choice-related activity in sensory cortex changes across learning and whether this activity is causally related to behavior. Identifying the dynamics and behavioral role of choice-predictive neurons would be a step towards linking neural activity with behavior and developing more effective BMIs. Here, I propose a series of experiments that overcome prior technological limitations and seek to clarify the role of choice-related activity in sensory cortex. Using two-photon calcium imaging, transgenic animals, and cellular-resolution gain- and loss-of-function perturbations, I will test two hypotheses: (1) that training on an optical microstimulation task drives the formation of a stable population of choice-predictive neurons in mouse somatosensory cortex and (2) that perturbation of choice-predictive neurons in this task will perturb behavior. In Aim 1, I will develop a combined LED photostimulation and two-photon imaging setup and use it to train mice to perform a discrimination task using activity evoked by the LED in sensory cortex. As animals learn the task, I will monitor neural activity in the stimulated population with cellular resolution and characterize how choice-predictive neurons change across sessions. In Aim 2, I will apply cellular-resolution, gain- and loss- of-function perturbations to choice-predictive neurons and assess how these perturbations affect task performance. These experiments will enhance our understanding of choice-related activity in sensory cortex and provide necessary insight into the link between neural activity and behavior.

项目摘要 由于截肢，中风或脊髓损伤引起的功能肢体损失对 生活质量。脑机界面（BMI）提供了一种通过为患者提供的恢复功能降低功能的方法 自愿控制假肢。但是，大多数这样的BMI都缺乏体感反馈，这 严重限制了他们的效率。神经的体感反馈仍然存在的主要原因 假体是，我们尚未了解感觉皮层中神经活动与 行为。一种将神经活动与行为相关的方法是研究与选择相关的活动 感觉皮层。与选择相关的活动是神经活动，可用于预测动物的行为选择 并已在许多感觉区域中被确定为动物执行各种行为任务。然而， 由于技术局限性，尚不清楚感觉皮质中与选择相关的活动如何变化 在学习以及这项活动是否与行为有关。识别动态和行为 选择预测性神经元的作用将是将神经元活动与行为和发展联系起来的一步 更有效的BMI。在这里，我提出了一系列实验，以克服先前的技术限制和 寻求阐明与选择相关活动在感觉皮层中的作用。使用两光子钙成像，转基因 动物以及细胞分辨率的增益和功能丧失扰动，我将检验两个假设：（1） 有关光学微刺激任务的培训推动了稳定的选择预测人群的形成 鼠标体感皮质中的神经元和（2）在此任务中选择预测性神经元的扰动将 扰动行为。在AIM 1中，我将开发一个组合的LED光刺激和两光子成像设置和 使用它来训练小鼠，使用LED在感觉皮层中引起的活动执行歧视任务。作为动物 了解任务，我将通过细胞分辨率监测受刺激人群中的神经元活动 选择性预测性神经元如何改变会议。在AIM 2中，我将应用细胞分辨率，增益和损失 - 对选择预测性神经元的扰动和评估这些扰动如何影响任务 表现。这些实验将增强我们对感觉皮层中与选择相关的活动的理解， 提供对神经活动与行为之间联系的必要洞察力。