Functional Properties of Neuronal Nicotinic Receptors

烟碱型乙酰胆碱受体（nAChR）位于许多脑区域中，并且已知其参与神经元的功能。 关键任务，包括学习，记忆和视觉。外源性应用nAChRs激活 乙酰胆碱（ACh）或尼古丁产生不同的功能反应。突触前nAChRs介导 增强了几种神经递质的释放。突触后nAChRs的激活产生兴奋性 这些反应足以引发神经元中的动作电位。尽管这些发现是至关重要的， 重要的是，关于内源性释放的乙酰胆碱的功能作用， 以及视觉系统和基底神经节中生理学重要途径的胆碱能调节。 本提案的主要目的是加强我们对烟碱受体的整体影响的理解， 内源性乙酰胆碱对脑切片内特定部位突触传递的激活。主要特点 我们的方法包括使用特征良好的模型系统（腹侧膝状体和侧 突触前和突触后烟碱反应，以及我们检查 烟碱调节的生理学意义是由电刺激释放 内源性乙酰胆碱在这些大脑区域的回路中定位nAChR亚型将使我们能够 构建一个模型，说明它们在处理输入信息和输出投射信息中的作用 神经元将使用全细胞膜片钳电生理记录进行功能研究， 大脑切片中的单个神经元活动。胆碱能传递对烟碱和毒蕈碱的影响 受体与谷氨酸能和GABA能传递的关系进行评价。我们将研究 烟碱受体激活的短期和长期效应，并研究发育调节 胆碱能调节。 在美国，吸烟每年导致超过40万人过早死亡。尼古丁是一种 在烟草中的原则，并在中央nAChRs的行为，以创造依赖性。尼古丁受体也介导 增强认知和视觉注意力，并且在几种神经退行性疾病中数量减少。 它们以高密度存在于视觉系统和基底神经节中，但它们在这些神经系统中的功能作用是重要的。 系统了解不多。该项目将扩大我们对这些受体作用的了解。

Nicotinic acetylcholine receptors (nAChRs) are located in many brain regions and are known to participate in critical tasks including learning, memory, and vision. Activation of nAChRs by exogenous application of acetylcholine (ACh) or nicotine produces diverse functional responses. Presynaptic nAChRs mediate enhanced release of several neurotransmitters. Activation of postsynaptic nAChRs produces excitatory responses that can be sufficient to elicit action potentials in neurons. Although these findings are critically important, relatively little is known concerning the functional effects of endogenously released acetylcholine and the cholinergic modulation of physiologically important pathways in the visual system and basal ganglia. The major goal of this proposal is to enhance our understanding of the overall impact of nicotinic receptor activation by endogenous ACh on synaptic transmission at defined sites within brain slices. Key featuresof our approach include the use of well-characterized model systems (ventral lateral geniculate and lateral spiriform nucleus) with robust presynaptic and postsynaptic nicotinic responses, and our ability to examine the physiological significance of nicotinic modulation resulting from the electrically stimulated release of endogenous ACh. Localization of nAChR subtypes within the circuitry of these brain regions will allow us to construct a model for their roles in the processing of incoming information and the output of projection neurons. Functional studies will be done using whole cell patch-clamp electrophysiological recordingsof single neuron activity in brain slices. The impact of cholinergic transmission at both nicotinic and muscarinic receptors will be evaluated in relationship to glutamatergic and GABAergic transmission. We will examine both short term and long term effects of activation of nicotinic receptors, and study developmental regulation of cholinergic modulation. Cigarette smoking causes over 400,000 premature deaths per year in the USA. Nicotine is the addictive principle in tobacco, and acts at central nAChRs to create dependence. Nicotinic receptors also mediate enhanced cognition and visual attention, and are reduced in number in several neurodegenerative diseases. They are present at high densities in the visual system and basal ganglia, but their functional roles in these systems are poorly understood. This project will expand our knowledge of the roles of these receptors.