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NICOTINIC MODULATION OF SENSORY TRANSMISSION

烟碱对感觉传递的调节

基本信息

批准号：
6649284
负责人：
JONATHAN ROBERT GENZEN
金额：
$ 5.3万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-15 至 2004-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6649284
关键词：
gene expression immunocytochemistry laboratory rat neural transmission neurons nicotinic receptors polymerase chain reaction protein structure function receptor expression spinal ganglion tissue /cell culture voltage /patch clamp

项目摘要

Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central nervous system, and are active in a wide array of physiological phenomena including addiction, cognition, locomotion, autonomic function, and sensation. While a role for nAChRs in these activities is clear from the pharmacological action of cholinergic agonists, the physiological role of specific nAChR subtypes in these processes is often unresolved. Neuronal nAChRs are pentameric ion channels composed of a variety of alpha and beta subunits, and the specific subunit combination can have a dramatic impact on channel properties including agonist and antagonist selectivity profiles, as well as the kinetics of activation, inactivation, and desensitization. The proposed research plan describes a set of experiments designed to study nAChR subunit expression in dorsal root ganglia (DRG) and the spinal cord dorsal horn (SC). The experiments will also examine the physiological role of specific receptor subtypes in the modulation of nociceptive processing. Whole-cell patch clamp recordings of neurons will be used to characterize the functional nAChRs expressed in these cells. Corroborative evidence will come from single-cell RT-PCR analysis of mRNA expression in recorded neurons, as well as immunohistochemistry of neurons in culture and tissue slices. Finally, spinal cord slices and neuronal co-cultures will be used to directly assay the modulation of synaptic transmission between DRG and SC neurons.

神经型烟碱型乙酰胆碱受体(NAChRs)广泛表达于中枢神经系统，参与成瘾、认知、运动、自主神经功能和感觉等多种生理现象。虽然从胆碱能激动剂的药理作用来看，nAChRs在这些活动中的作用是明确的，但特定的nAChR亚型在这些过程中的生理作用往往还没有解决。神经元nAChRs是由各种α和β亚基组成的五聚体离子通道，特定的亚基组合可以对通道特性产生重大影响，包括激动剂和拮抗剂的选择性分布，以及激活、失活和脱敏的动力学。拟议的研究计划描述了一系列实验，旨在研究nAChR亚单位在背根节(DRG)和脊髓背角(SC)的表达。这些实验还将检验特定受体亚型在伤害性信息处理中的生理作用。神经元的全细胞膜片钳记录将被用来表征在这些细胞中表达的功能性nAChRs。确凿的证据将来自对记录的神经元中mRNA表达的单细胞RT-PCR分析，以及培养和组织切片中神经元的免疫组织化学。最后，脊髓切片和神经元共培养将被用来直接分析DRG和SC神经元之间突触传递的调节。