Divergence of Tactile Processing in the Dorsal Column Nuclei

项目摘要 支配皮肤的不同种类的感觉神经元构成了我们感知不同范围的能力的基础 并为我们提供操纵对象、检测威胁和导航我们的 环境。尽管我们的触觉很重要，但我们对接受者是如何 脑干背侧柱核(DCN)中的神经元整合初级感觉信息，以及如何 然后，经过处理的信息被传输到大脑。解剖学追踪研究揭示了多个非 DCN下游靶点重叠，最突出的是丘脑和下丘。AS 我推测，来自外周和中枢躯体感觉通路的感觉信息之间的结点 DCN作为差异感觉整合的场所，选择性地调节输出路径与特征 在环境中。我提议的实验将通过表征调谐特性来解决这一假设 以下丘和丘脑为靶点的DCN投射神经元，并通过研究 反应由外周感觉神经元和抑制性中间神经元的输入构成。这项工作将 通过将新的脑干记录方法与工具相结合来操作 初级感觉神经元的活动。通过这样做，我的建议将对DCN如何处理提供深入的见解 触觉信息，也可能阐明大脑组织感觉的更一般机制 信息。此外，对早期躯体感觉过程的基本理解将有助于努力 开发神经假体，并指导治疗躯体感觉改变的临床病例，如 如周围神经损伤后的机械性痛觉异常或个体表现出的光触觉过敏 患有自闭症。

Project Summary The diverse range of sensory neurons that innervate the skin underlie our ability to perceive a remarkable range of tactile stimuli and provide us with the capacity to manipulate objects, detect threats, and navigate our environment. Despite the fundamental importance of our sense of touch, little is known about how recipient neurons in the dorsal column nuclei (DCN) of the brainstem integrate primary sensory information, and how processed information is then transmitted to the brain. Anatomical tracing studies have revealed multiple, non- overlapping downstream targets of the DCN, the most prominent being the thalamus and inferior colliculus. As the node between sensory information from the periphery and central somatosensory pathways, I hypothesize that the DCN functions as a site of differential sensory integration to selectively tune output pathways to features in the environment. My proposed experiments will address this hypothesis by characterizing the tuning properties of DCN projection neurons that target the inferior colliculus and the thalamus, and by investigating how responses are constructed by inputs from peripheral sensory neurons and inhibitory interneurons. This work will overcome barriers in the field by combining novel brainstem recording methods with tools to manipulate the activity of primary sensory neurons. In doing so, my proposal will yield insights into how the DCN processes tactile information, and may also illuminate more general mechanisms by which the brain organizes sensory information. Additionally, a fundamental understanding of early somatosensory processing will inform efforts to develop neural prosthetics, as well as guide efforts to treat clinical cases where somatosensation is altered, such as mechanical allodynia after peripheral nerve injury or hypersensitivity to light touch exhibited by individuals with autism.