Spatiotemporal Coding in the Pain Circuit Along the Spine-brain Continuum

摘要/摘要 疼痛是一个全国性的健康挑战，每年给我们的经济造成6000多亿美元的损失。面临着 无效的治疗，数百万患者正在过量开阿片类药物，这是 导致上瘾和致命的服药过量。 该应用程序是对RFA-NS-18-009《Brain Initiative：针对性脑电路项目》的响应 (R01)“呼吁”确定和理解的创新方法和新范式 中枢神经系统回路机制中的伤害性和疼痛“。 我们建议1)开发工具来检验板层II/III PV神经元抑制的假说 体内伤害性中继神经元，目的2)行为发育以验证快速报告的新模型 3)来自脊椎-大脑连续体的实时神经记录和 生态行为来验证这样的假设，即感觉丘脑和新皮质的不同节律是 在时间上与触觉和伤害性刺激相关。此外，兴奋PV神经元抑制丘脑 神经元和调节丘脑皮质节律。 将使用疼痛的实验室动物模型和最先进的技术来研究这些目标 从脊髓和脑的多个区域同时记录，结合细胞特异性fic刺激 在周围使用光学方法唤醒啮齿动物。因此，此应用程序将增强我们的科学fic 了解中枢神经系统中的疼痛机制，并可能导致新的诊断和 治疗方法。

Summary/Abstract Pain is a national health challenge costing our economy more than $600 Billions per year. Faced with ineffective therapies, millions of patients are being over-prescribed opioid-based medications, which is contributing to addiction and lethal overdose. This application is in response to RFA-NS-18-009 “BRAIN Initiative: Targeted BRAIN Circuits Projects (R01)” which calls for “Innovative approaches and new paradigms for identifying and understanding nociception and pain in the context of circuit mechanisms of the central nervous system”. We propose AIM 1) tool development to test the hypothesis that Laminae II/III PV neurons inhibit nociceptive relay neurons in vivo, AIM 2) behavioral development to validate a novel model for rapid reporting of sensory stimuli, and AIM 3) combination of real-time neural recording from the spine-brain continuum and ecological behavior to test the hypothesis that distinct rhythms in sensory thalamus and neocortex are temporally correlated with tactile and noxious stimuli. Moreover, excitation of PV neurons inhibits thalamic neurons and modulates thalamocortical rhythms. These aims will be investigated using laboratory animal models of pain and state-of-the-art techniques for simultaneous recording from multiple areas in the spine cord and brain, combined with cell-specific stimulation in the periphery using optical methods in awake rodents. Therefore, this application will enhance our scientific understanding of pain mechanisms in the central nervous system and potentially lead to novel diagnostic and therapeutic approaches.