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.

项目概要 由于截肢、中风或脊髓损伤而丧失功能性肢体会给人们带来毁灭性的后果 生活质量。脑机接口 (BMI) 提供了一种通过为患者提供恢复失去的功能的方法 能够自主控制假肢。然而，大多数此类 BMI 缺乏体感反馈，这使得 严重限制了它们的功效。神经系统仍然缺乏体感反馈的一个主要原因 假肢的问题在于我们尚未了解感觉皮层的神经活动与 行为。将神经活动与行为联系起来的一种方法是研究与选择相关的活动 感觉皮层。选择相关活动是可用于预测动物行为选择的神经活动 当动物执行各种行为任务时，已在许多感觉区域中发现了这种现象。然而， 由于技术限制，目前尚不清楚感觉皮层中与选择相关的活动如何变化 跨学习以及该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并发展的一步 更有效的 BMI。在这里，我提出了一系列克服现有技术限制的实验 试图阐明感觉皮层中与选择相关的活动的作用。使用双光子钙成像，转基因 动物，以及细胞分辨率获得和功能丧失的扰动，我将测试两个假设：（1） 光学微刺激任务的训练推动了稳定的选择预测群体的形成 小鼠体感皮层中的神经元以及（2）在该任务中对选择预测神经元的扰动将 扰乱行为。在目标 1 中，我将开发一种组合式 LED 光刺激和双光子成像装置， 使用它来训练小鼠利用 LED 在感觉皮层中引起的活动来执行辨别任务。作为动物 学习任务后，我将通过细胞分辨率监测受刺激群体的神经活动并表征 选择预测神经元在不同会话中如何变化。在目标 2 中，我将应用细胞分辨率、增益和损耗 对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 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 提供对神经活动和行为之间联系的必要见解。