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

项目总结 截肢、中风或脊髓损伤导致的功能性肢体丧失对 生活质量。脑机接口(BMI)提供了一种通过为患者提供 对假肢的自愿控制。然而，大多数这样的BMI缺乏体感反馈，这 严重限制了它们的疗效。神经缺乏体感反馈的一个主要原因 假体是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与选择相关的活动 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 当动物执行各种行为任务时，已经在许多感官区域被发现。然而， 由于技术的限制，尚不清楚感觉皮层中与选择相关的活动是如何变化的。 跨学习，以及这种活动是否与行为有因果关系。确定动态和行为 选择预测神经元的作用将是将神经活动与行为和发育联系起来的一步 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，并 试图阐明与选择相关的活动在感觉皮质中的作用。使用双光子钙成像，转基因 动物，以及细胞分辨率获得和丧失功能的扰动，我将测试两个假设：(1) 视觉微刺激任务训练推动稳定选择人群的形成--预测性 小鼠躯体感觉皮层的神经元和(2)在这项任务中选择预测神经元的扰动 烦躁不安的行为。在目标1中，我将开发一种LED光刺激和双光子成像相结合的装置，并 用它来训练小鼠使用LED在感觉皮质中诱发的活动来执行辨别任务。作为动物 学习这项任务，我将用细胞分辨率监测刺激人群中的神经活动，并表征 选择预测神经元在不同阶段是如何变化的。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函数扰动以及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和大脑中与选择相关的活动的理解 对神经活动和行为之间的联系提供必要的洞察。

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.