Thalamic and Cortical Mechanisms of Itch

 描述（由申请人提供）：瘙痒是一种常见的临床问题，通常难以治疗。目前对CNS中产生瘙痒的机制了解甚少，这可能导致无法治疗瘙痒。近年来，人们越来越清楚地认识到，与瘙痒相关的信息是由神经元在外周和脊髓中传递的，这些神经元也被伤害性刺激激活。这表明，在大脑中产生瘙痒所必需的信息必须在一个称为解码的过程中从多感觉神经元的反应中提取。拟议中的研究将首次使用单单位电生理学技术来确定丘脑和皮层中处理记忆信息的区域。将测定丘脑中单个神经元对各种瘙痒和疼痛产生刺激的反应。将使用逆向激活方法来确定丘脑神经元投射的皮质区域。此外，还将确定单个皮质神经元对促神经生长剂和疼痛产生刺激的反应。拟议的研究将确定丘脑核团和皮层区域，在这些区域中发生与瘙痒和疼痛相关的信息处理。此外，使用机器学习方法，我们将确定反应中动作电位的强度和模式的贡献 瘙痒和疼痛相关反应的差异编码。拟议的研究将大大扩展我们对产生瘙痒和疼痛的中枢神经系统机制的理解。 相关性：关于丘脑和大脑皮层中产生痒感的神经系统，我们知之甚少。这种缺乏了解可能会导致 大多数类型的慢性瘙痒缺乏有效的治疗方法。拟议的研究 将决定丘脑和皮层中单个神经元处理和传递瘙痒和疼痛信息的区域。

 DESCRIPTION (provided by applicant): Itch is a common clinical problem that is often difficult to treat. There is currently little understanding of the mechanism used in the CNS to produce itch and this likely contributes to the inability to treat itch. In recent years it have become cler that information related to itch is carried in the periphery and spinal cord by neurons that are also activated by noxious stimuli. This suggests that information necessary for the production of itch in the brain must be extracted from the responses of polysensory neurons in a process called decoding. The proposed studies, will for the first time, use single unit electrophysiologica techniques to determine the areas in the thalamus and cortex where processing of pruriceptive information occurs. The responses of single neurons in the thalamus to various itch-and pain-producing stimuli will be determined. The cortical areas to which pruriceptive thalamic neurons project will be determined using antidromic activation methods. In addition, responses of individual cortical neurons to pruritogens and pain-producing stimuli will be determined. The proposed studies will determine the thalamic nuclei and cortical areas in which processing of information related to itch and pain occur. In addition, using a Machine Learning approach, we will determine the contributions of the intensity and pattern of action potentials within responses to differential coding of itch and pain related responses. The proposed studies will considerably expand our understanding of the CNS mechanisms that produce itch and pain. RELEVANCE: Very little is known about the neural systems in the thalamus and cerebral cortex that underlie production of the sensation of itch. This lack of understanding likely contributes to the paucity of effective treatments for the majority of types of chronic itch. The proposed studies will determine the areas in the thalamus and cortex in which single neurons process and transmit information about itch and pain.