SEROTONERGIC CONTROL OF SPINAL CORD NEUROTRANSMISSION

脊髓神经传递的血清素控制

• 批准号: 2036461
• 负责人: PETER A GOLDSTEIN
• 金额: $ 8.29万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2036461
• 关键词: NMDA receptors; action potentials; calcium flux; calcium indicator; calcium ion; charge coupled device camera; digital imaging; dorsal horn; excitatory aminoacid; fluorescence microscopy; glutamates; laboratory rat; neural transmission; neurons; neuroregulation; neurotransmitter agonist; pain; sensory receptors; serotonin; serotonin inhibitor; serotonin receptor; spinal cord; synapses; tissue /cell culture; voltage /patch clamp; voltage gated channel

The long-term objective of this grant is to further understand the cellular mechanisms underlying the pathophysiology of both acute and chronic pain states. The neurophysiological mechanisms underlying the transmission and processing of nociceptive, or painful, stimuli within the central nervous system remain poorly understood. Multiple neurotransmitter system are thought to be involved in the transmission of pain signals, including but not limited to those mediated by glutamate and serotonin (5- HT). Although substantial evidence exists implicating glutamate as the principle neurotransmitter responsible for excitatory transmission, the direct and.or regulatory effects of the 5-HT system on the glutamatergic system are well defined. The overall purpose of this project is to help further define the interactions between the glutamatergic and 5-HT transmitter systems in the spinal chord so as to obtain a clearer understanding of the processes that regulate nociceptive afferent neurotransmission. To investigate how glutamatergic neurotransmission is regulated by 5-HT, an in vitro preparation will be used. Pre-synaptic stimulation is achieved by stimulating the dorsal root and post-synaptic whole-cell recordings are made from visually identified single neurons in the substantia gelatinosa using the patch clamp technique. Briefly, a thin transverse section of spinal cord with dorsal roots attached is obtained from post-natal rat pup. The spinal cord slice is then superfused in an extracellular bath solution containing selective agonists and antagonists for specific 5-HT receptor subtypes while recording dorsal root-evoked post-synaptic events. Proceeding in this manner will enable us to identify which 5-HT receptor subtypes modulate glutamatergic transmission. Once the receptor subtypes are identified, the site(s) of action, pre-and/or post-synaptic, will be identified. The results will hopefully provide new insights into the mechanisms of pain transmission as well as suggest novel methods for providing analgesia in both the acute and chronic setting.

这笔赠款的长期目标是进一步了解 急性和慢性疾病病理生理学的细胞机制 慢性疼痛状态。其背后的神经生理学机制 伤害性或痛苦性刺激的传输和处理 中枢神经系统仍然知之甚少。多种神经递质 系统被认为参与疼痛信号的传递， 包括但不限于谷氨酸和血清素（5- HT）。尽管有大量证据表明谷氨酸是 负责兴奋性传递的主要神经递质 5-HT系统对谷氨酸能的直接和/或调节作用 系统定义明确。该项目的总体目的是帮助 进一步定义谷氨酸能和5-HT之间的相互作用 脊髓中的发射器系统，以获得更清晰的信息 了解调节伤害性传入的过程 神经传递。 为了研究 5-HT 如何调节谷氨酸能神经传递， 将使用体外制剂。实现突触前刺激 通过刺激背根和突触后全细胞记录 由肉眼识别的凝胶质中的单个神经元制成 使用膜片钳技术。简而言之，薄的横截面 附有背根的脊髓取自产后大鼠 小狗。然后将脊髓切片注入细胞外浴中 含有特定 5-HT 选择性激动剂和拮抗剂的溶液 受体亚型，同时记录背根诱发的突触后事件。 以这种方式进行将使我们能够识别哪种 5-HT 受体 亚型调节谷氨酸能传递。一旦受体亚型 确定后，突触前和/或突触后的作用位点将被确定 确定。 研究结果有望为机制提供新的见解 疼痛传递并提出提供镇痛的新方法 在急性和慢性环境中。