Dopaminergic modulation of CA1 intrinsic excitability

CA1 内在兴奋性的多巴胺能调节

• 批准号: 6634372
• 负责人: Nathan P Staff
• 金额: $ 5.3万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6634372
• 关键词: amphetamines; behavior test; brain electrical activity; chemosensitizing agent; dendrites; dopamine; drug addiction; electrical conductance; electrical measurement; hippocampus; laboratory rat; membrane potentials; neural plasticity; neuroanatomy; neuropharmacology; neuroregulation; pyramidal cells; sectioning; sodium channel; synapses; tissue /cell preparation; voltage /patch clamp; voltage gated channel

Understanding the mechanisms of drug addiction is a major goal of modern neurobiology. At the heart of the problem lies an alteration in the dopaminergic neuromodulatory system. The hippocampus is a region of the brain that has been implicated in drug reward circuitry, and is heavily innervated by ventral tegmental dopaminergic terminals. Recently, much attention has been devoted to voltage-gated ion channels in the dendrites of CA1 pyramidal neurons of the hippocampus, yet little of this attention has focused on its possible importance. In drug addiction. My preliminary evidence suggests that voltage-gated ion channels in CA1 neurons can undergo plastic changes following synaptic conditioning., which is a particularly interested phenomenon considering that alterations in intrinsic excitability of neurons have been reported in nucleus accumbal neurons following psychostimulant sensitization. In this proposal the goal is to understand how plasticity of dendritic intrinsic conductances could contribute to the neuroadaptation seen during drug addiction. Specifically, I plan to explore acute and chronic dopaminergic modulation of CA1 pyramidal dendritic function using both in vitro and in vitro pharmacological manipulations.

了解药物成瘾的机制是现代神经生物学的主要目标。问题的核心是多巴胺能神经调节系统的改变。海马是大脑的一个区域，与药物奖励回路有关，并通过腹侧换扇形多巴胺能末端支配。最近，在海马的Ca1锥体神经元的树突中，已经非常关注电压门控离子通道，但这种关注很少关注其可能的重要性。在吸毒成瘾中。我的初步证据表明，CA1神经元中的电压门控离子通道可以在突触调节后经历塑性变化。考虑到，在心理刺激性敏化后，已经报道了在副不见的神经元中据报道神经元内固有兴奋性的改变。在此提案中，目标是了解树突固有电导的可塑性如何有助于吸毒期间看到的神经适应。具体而言，我计划使用体外和体外药理操作探索CA1锥体树突状功能的急性和慢性多巴胺能调节。