MECHANISMS OF LOCAL SYNAPTIC TRANSMISSION IN DORSAL HORN

背角局部突触传递机制

• 批准号: 6187191
• 负责人: STEPHEN P SCHNEIDER
• 金额: $ 22.42万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 2003-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187191
• 关键词: Rodentias; confocal scanning microscopy; dorsal horn; electrophysiology; hyperalgesia; immunocytochemistry; infrared microscopy; interneurons; neural conduction; neural plasticity; neural transmission; neuropharmacology; sensorimotor system; single cell analysis; somesthesis; spinal cord mapping; spinal nerves; synapses

DESCRIPTION: (Adapted from the Investigator's Abstract) The long-term objective of this project is to determine the neural mechanisms of integrative function in local synaptic circuits of the deep spinal dorsal horn (Rexed's laminae III-V). The ultimate goal is a better understanding of basic mechanisms underlying normal somesthesis and spread of hyperexcitability in neurological models of hyperalgesia. The specific aims build upon our previous work which shows that laminae III-V neurons express firing behavior related to cutaneous mechanosensory afferent input and efferent synaptic organization and can exhibit persistent hyperexcitability following brief direct activation. Experiments will test the general hypotheses that i) neurons in laminae III-V are organized into circuits according to intrisnsic electrophysiological properties of the pre- and postsynaptic cells and ii) induction of hyperexcitability in laminae III-V neurons alters integrative function, increasing responsiveness to natural sensory stimulation and local synaptic input. The following project aims are proposed: Determine the spike-frequency adaptation properties and signaling characteristics of synaptically-linked interneurons in laminae III-V of the dorsal horn. Determine the nature of synaptic connections between interneurons in laminae III-V, whether excitatory or inhibitory, or both. Determine whether the persistent membrane depolarization and firing augmentation evoked in laminae III-V interneurons is accompanied by increases in responsiveness to natural sensory stimulation increases and local synaptic inputs. These aims will be accomplished using isolated preparation of rodent thoracolumbar spinal cord that facilitate access to small interneurons with intact sensory input. Synaptic connections between neurons will be investigated directly using dual whole-cell recording methodology and pharmacological antagonists of synaptic function. Immunocytochemistry and laser scanning confocal microscopy will be used to anatomically localize synaptic markers in physiologically identified neurons. The results will advance knowledge of spinal mechanisms of somethesis and contribute to understanding of painful sensory sequelae of spinal cord and peripheral injury, including secondary hyperalgesia and allodynia.

描述：（根据调查员的摘要进行了改编）长期目标 这个项目的是确定整合功能的神经机制 在深脊髓角的局部突触中（Rexed的Laminae III-V）。最终目标是更好地理解基本机制 基本的正常体现和过度兴奋性神经系统的传播 痛觉过敏的模型。具体目标是基于我们以前的工作 表明Laminae III-V神经元表达与皮肤有关的发射行为 机械感应传入输入和传出突触组织，可以 短暂直接激活后表现出持久的过度兴奋性。 实验将测试一般假设，即I）laminae III-V中的神经元 根据杂文电生理学将其组织成电路 突触前和突触后细胞的特性，ii）诱导 Laminae III-V神经元中的过度兴奋性改变了整合功能， 对自然感觉刺激和局部突触的反应性提高 输入。提出了以下项目目标： 确定尖峰频率适应性和信号传导 突触连接的中间神经元在laminae III-V中的特征 背角。 确定层中间神经元之间突触连接的性质 III-V，无论是兴奋性还是抑制性，还是两者兼而有之。 确定持续的膜去极化和发射 在Laminae III-V中间神经元中引起的增强伴随着增加 在对自然感觉刺激的反应中增加和局部突触 输入。 这些目标将使用啮齿动物的孤立制备来实现 胸骨脊髓，促进与小型中间神经元的使用 完整的感觉输入。将研究神经元之间的突触连接 直接使用双电池记录方法和药理学 突触功能的拮抗剂。免疫细胞化学和激光扫描 共聚焦显微镜将用于解剖位置突触标记 生理上鉴定的神经元。结果将提高知识 物质的脊柱机制，有助于理解痛苦 脊髓和周围损伤的感觉后遗症，包括次级 痛苦和异常性痛。