CENTRAL NICOTINIC CHANNEL KINETICS AND SYNAPTIC FUNCTION

这项提案的目的是调查两国之间的互动 神经递质、乙酰胆碱(ACh)和中枢烟碱 胆碱能受体(NAChR)通道，以了解其功能 中枢神经系统(CNS)的烟碱能突触传递。 尽管有强有力的神经化学证据表明某些胆碱能通路 投射到富含nAChRs的大脑区域，几乎没有关于 NAChRs参与突触传递的研究已经通过 传统的生理学技术。在不能 直接检查中枢尼古丁突触，将采取不同的策略 必填项。该方案的总体实验设计是基于 传送器(如ACH)快速释放和 清除了突触裂隙。使用快速灌流技术，脉冲 将应用于小细胞和由外向外的贴片中的nAChRs。 因此，ACH将以以下方式快速激活nAChRs 类似于突触刺激。这种方法将提供一种强大的 研究nAChR通道相对于 真实突触反应的特性。这些实验将具体地 包括ACh与nAChRs快速结合的评估、激活 和开放nAChR通道，烟碱能突触的持续时间 反应和nAChRs返回其休眠状态。此外 对于这些研究，中枢胆碱能神经元的原代培养将是 开发的目的是激活突触前和突触后位置的nAChRs 直接接受检查。 突触传递是神经元 神经元的输出在很大程度上取决于 整合它接收到的各种传入突触信号。这个 突触反应的特殊特征，由相互作用决定 在接收器和传输器之间，将控制信号的影响 会对神经元的整体特性产生影响。因此，一门学问 NAChRs突触激活的基本特征 ACH对于理解这两种正常功能都是非常有价值的 胆碱能系统在突触传递和可塑性中的作用 胆碱能神经元丢失在某些退行性疾病中的全部意义 疾病。

The objectives of this proposal are to investigate the interaction between the neurotransmitter, acetylcholine (ACh), and central nicotinic cholinergic receptor (nAChR) channels, in order to understand the function of nicotinic synaptic transmission in the central nervous system (CNS). Despite strong neurochemical evidence that certain cholinergic pathways project to brain regions rich in nAChRS, little information regarding the participation of nAChRs in synaptic transmission has been obtained using conventional physiological techniques. In the absence of being able to examine central nicotinic synapses directly, a different strategy will be required. The overall experimental design of this proposal is based on the general principal that transmitters, such as ACh, are rapidly released and cleared from the synaptic cleft. Using rapid perfusion techniques, pulses of ACh will be applied to nAChRs in small cells and outside-out patches. Thus, nAChRs will be rapidly activated by ACh in a manner that is analogous to synaptic stimulation. This approach will provide a powerful means of studying the behavior of nAChR channels with respect to the properties of a real synaptic response. The experiments will specifically include, evaluation of the rapid binding of ACh to nAChRs, the activation and opening of nAChR channels, the duration of the nicotinic synaptic response and the return of the nAChRs to their resting state. In addition to these studies, primary cultures of central cholinergic neurons will be developed so that activation of nAChRs at pre- and post-synaptic sites can be examined directly. Synaptic transmission is the primary means through which neurons communicate and the output of a neuron is determined largely by integrating the varied incoming synaptic signals it receives. The particular features of a synaptic response, determined by the interaction between receptor and transmitter, will control the influence that signal will have on the overall properties of the neuron. Therefore, a knowledge of the fundamental characteristics of the synaptic activation of nAChRs by ACh would be invaluable in the understanding of both the normal function of the cholinergic system in synaptic transmission and plasticity, and the full implications of cholinergic neuronal loss in certain degenerative diseases.