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、中风或脊髓损伤而导致的功能性肢体的丧失， 生活质量脑机接口（BMI）提供了一种通过为患者提供 通过对假肢的自主控制。然而，大多数这样的BMI缺乏体感反馈， 严重限制了它们的功效一个主要的原因体感反馈仍然缺乏神经 我们还没有弄清楚感觉皮层的神经活动和 行为将神经活动与行为联系起来的一种方法是研究选择相关的活动， 感觉皮层选择相关活动是可以用来预测动物行为选择的神经活动 并且已经在动物执行各种行为任务时的许多感觉区域中被确定。然而，在这方面， 由于技术上的限制，目前还不清楚感觉皮层中与选择有关的活动是如何变化的。 以及这种活动是否与行为有因果关系。识别动态和行为 选择预测神经元的作用将是将神经活动与行为联系起来的一步， 更有效的BMI。在这里，我提出了一系列的实验，克服了以前的技术限制， 试图阐明选择相关活动在感觉皮层中的作用。使用双光子钙成像，转基因 动物，和细胞分辨率增益和功能丧失扰动，我将测试两个假设：（1）， 光学微刺激任务的训练驱动了一个稳定的选择预测群体的形成， （2）在这项任务中，选择预测神经元的扰动将 扰乱行为在目标1中，我将开发一种组合的LED光刺激和双光子成像装置， 用它来训练老鼠执行识别任务，使用LED在感觉皮层中诱发的活动。像动物 学习任务，我将监测神经活动的刺激人口与细胞的分辨率和特点 选择预测神经元在不同阶段的变化。在目标2中，我将应用细胞分辨率，增益和损失， 选择预测神经元的功能扰动，并评估这些扰动如何影响任务 性能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， 为神经活动和行为之间的联系提供了必要的见解。