Spinal Sensory Ganglia and Gut Sensation

脊髓感觉神经节和肠道感觉

• 批准号: 10320527
• 负责人: Ivan E de Araujo
• 金额: $ 59.21万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10320527
• 关键词: Address; Afferent Neurons; Anatomy; Animals; Anorexia; Area; Behavior; Behavioral; Behavioral Assay; Brain; Brain Mapping; Cell Nucleus; Cells; Chemicals; Chronic; Clinical; Cognitive; Communication; Computers; Disease; Electrophysiology (science); Emotional; Esthesia; FOS gene; Fatigue; Feeling; Functional disorder; Ganglia; Gastrointestinal Motility; Injections; Interneurons; Interoception; Lateral; Light; Link; Maps; Mechanics; Mechanoreceptors; Mediating; Methodology; Microscopy; Molecular; Mus; Musculoskeletal; Nausea; Neurons; Neurosciences; Opsin; Optics; Organ; Parietal; Pathway interactions; Perception; Peripheral; Physiological; Play; Proprioception; Reticular Formation; Rewards; Role; Satiation; Sensory; Sensory Ganglia; Signal Transduction; Source; Spinal; Spinal Cord; Spinal Ganglia; Stimulus; Stomach; Stretching; Substance abuse problem; Testing; Tracer; Vagus nerve structure; Viral; awake; base; brain circuitry; brain pathway; combinatorial; design; detection of nutrient; experimental study; gastrointestinal; gut-brain axis; in vivo; mechanotransduction; motility disorder; nerve supply; nervous system disorder; neural circuit; novel; optogenetics; pressure; psychologic; psychosocial; receptor; therapeutic target

Project Summary The gut-brain axis, and in particular brain-stomach communication, are implicated in emotional and cognitive processing and often linked to many nervous system disorders, including psychosocial dysfunction, substance abuse, neurological diseases, and degeneration. While a large body of work exists on stomach-brain vagal pathways, much less is known about how the brain and the stomach may communicate through the spinal sensory pathways. This R01 application proposes to determine the anatomy, function, and circuitry targeted by gut-innervating spinal sensory ganglia. The proposed studies will test the overarching hypothesis that, similarly to musculoskeletal proprioception, gastrointestinal (GI) mechanical stimuli are signaled to the brain, specifically the lateral reticular nucleus (LRN), via shared spinal sensory pathways. In addition, the proposal will determine the functional impact of the gastric-spinal-brain pathways on brain functions including reward behaviors and brain circuitries including the parietal, insular, and orbitofrontal cortices. To address our aims, state-of-the-art methodology will be used including organ-specific targeting by combinatorial viral injection, optogenetics including optically guided, in vivo electrophysiology in awake mice, computer-operated intraluminal balloon distension, and whole-brain c-Fos maps using light-sheet microscopy. Our studies may reveal novel peripheral therapeutical targets for emotional and psychosocial disorders associated with abnormal gut-brain communication. Moreover, the neural circuitries to be described in our studies may also be targeted to alleviate abnormal psychological states, including the nausea, anorexia, and chronic fatigue typical of GI motility disorders.

项目摘要 肠道轴，尤其是脑刺交流，与情感和认知处理有关，通常与许多神经系统疾病有关，包括心理社会功能障碍，药物滥用，神经系统疾病和退化。尽管大量工作存在于胃脑迷走神经途径上，但对大脑和胃可能如何通过脊柱感觉途径进行交流的知之甚少。该R01应用建议通过肠道脊柱感觉神经节靶向的解剖学，功能和电路。拟议的研究将检验总体假设，即与肌肉骨骼本体感受类似，胃肠道（GI）机械刺激通过共享的脊柱感觉途径发出了胃肠道（GI）的机械刺激，特别是侧面网状核（LRN）。此外，该建议将确定胃 - 脊柱脑途径对脑功能的功能影响，包括奖励行为和脑电路，包括顶叶，岛状和眶额皮质。为了解决我们的目标，将使用最先进的方法，包括组合病毒注射的器官特异性靶向，包括光学指导，包括光学指导的醒着小鼠的体内电生理学，计算机操作的计算机内的气球伸展，以及使用轻微秀的全脑C-FOS。我们的研究可能揭示了与异常肠脑沟通相关的情绪和社会心理疾病的新外围治疗靶标。此外，在我们的研究中要描述的神经循环也可能针对缓解异常的心理状态，包括恶心，厌食和典型的GI运动障碍的慢性疲劳。