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。问题的核心在于多巴胺能神经调节系统的改变。海马体是大脑中与药物奖赏回路有关的一个区域，由腹侧被盖多巴胺能终末严重支配。最近，人们对海马区CA1区锥体神经元树突中的电压门控离子通道进行了大量的研究，但很少有人关注其可能的重要性。吸毒成瘾。我的初步证据表明，突触条件作用后，CA1神经元的电压门控离子通道可以发生可塑性变化。这是一个特别有趣的现象，因为已有报道称，精神刺激剂敏化后伏核神经元的内在兴奋性发生了变化。在这项提议中，目标是了解树突状固有电导的可塑性如何有助于药物成瘾过程中的神经适应。具体地说，我计划使用体外和体外药理操作来探索急性和慢性多巴胺能对CA1锥体树突状细胞功能的调节。