NICOTINIC MODULATION OF SENSORY TRANSMISSION

神经元烟碱乙酰胆碱受体（nAChR）在整个中枢神经系统中表达，并且在包括成瘾、认知、运动、自主功能和感觉的广泛的生理现象中是活跃的。 虽然nAChR在这些活动中的作用从胆碱能激动剂的药理学作用中是清楚的，但特定nAChR亚型在这些过程中的生理作用通常未得到解决。神经元nAChR是由多种α和β亚基组成的五聚体离子通道，并且特定的亚基组合可以对通道特性（包括激动剂和拮抗剂选择性概况）以及激活、失活和脱敏的动力学具有显著影响。 拟议的研究计划描述了一组实验，旨在研究背根神经节（DRG）和脊髓背角（SC）的nAChR亚基的表达。 实验还将研究特定受体亚型在伤害性处理调制中的生理作用。 神经元的全细胞膜片钳记录将用于表征这些细胞中表达的功能性nAChR。 确证的证据将来自记录的神经元中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物将用于直接测定DRG和SC神经元之间突触传递的调节。

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.