SYNAPTIC MODULATION OF MESOPONTINE CHOLINERGIC NEURONS

中桥胆碱能神经元的突触调节

• 批准号: 2266628
• 负责人: CHRISTOPHER S LEONARD
• 金额: $ 15.3万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2266628
• 关键词: acetylcholine; brain electrical activity; brain mapping; central neural pathway /tract; guinea pigs; histochemistry /cytochemistry; membrane potentials; neural conduction; neural information processing; neuroanatomy; norepinephrine; pons; reticular formation; serotonin; synapses; tegmentum; thalamus; voltage /patch clamp

Considerable evidence indicates that the cholinergic input to the thalamus, which arises from the mesopontine tegmentum, plays a key role in the control of sleeping, dreaming and arousal. In addition, these cells are implicated in the normal control of locomotion and in the pathologies of Parkinson's disease, affective disorders and unconsciousness due to concussive brain injury. Nevertheless, little is known about the mechanisms controlling activity in these cholinergic afferents. The proposed experiments are designed to fill this void by providing electrophysiological evidence for interactions between the putative neurotransmitters acetylcholine, serotonin and norepinephrine on these cholinergic cells, as well as by providing evidence for synaptic control by these transmitter systems. The proposed experiments investigate the hypothesis that modulation of the biophysical properties of mesopontine cholinergic neurons is a key step in triggering alterations in behavioral state. This shall be investigated by in vitro cellular studies which will determine the cellular and synaptic properties of mesopontine cholinergic neurons and in vivo studies which will determine if alterations of these properties promote alterations in behavioral state. The results of these studies will provide the first detailed picture of the pharmacological and synaptic properties of identified mesopontine cholinergic neurons. Furthermore, by extending the analysis from the brainslice to the intact animal these studies will determine how signalling mechanisms identified in vitro function in the intact system. Accordingly, these results will have an important bearing on our understanding of brainstem mechanisms in the control of consciousness. These studies represent a first step toward the ultimate goal of understanding the neural basis of consciousness. An important future step will be to integrate these results into realistic models of brainstem and thalamic circuitry to investigate how the interplay between cellular properties and circuits generate global behavioral states.

大量证据表明胆碱能输入到丘脑， 源自中桥的支膜，在 控制睡眠，梦想和唤醒。 另外，这些细胞是 与运动的正常控制有关和 帕金森氏病，情感障碍和无意识 脑震荡的脑损伤。 然而，对 控制这些胆碱能传入的机制。 这 建议的实验旨在通过提供来填充此空隙 假定的相互作用的电生理证据 神经递质乙酰胆碱，5-羟色胺和去甲肾上腺素 胆碱能细胞以及通过提供突触控制的证据 这些发射器系统。 提出的实验研究了 假设间木座的生物物理特性调节 胆碱能神经元是触发行为改变的关键步骤 状态。 这应通过体外细胞研究来研究 确定间泊胆碱能的细胞和突触特性 神经元和体内研究将决定这些改变是否改变 属性促进行为状态的改变。 这些结果 研究将提供药理学和 鉴定的中桥胆碱能神经元的突触特性。 此外，通过将分析从脑层扩展到完整 动物这些研究将确定如何在 完整系统中的体外功能。 因此，这些结果将有 重要的是我们对脑干机制的理解 控制意识。 这些研究是迈向的第一步 理解意识神经基础的最终目标。 一个 重要的未来步骤将是将这些结果整合到现实 脑干和丘脑电路的模型，以研究如何相互作用 在细胞性质和电路之间产生全球行为状态。