Dopaminergic modulation of CA1 intrinsic excitability

CA1 内在兴奋性的多巴胺能调节

• 批准号: 6339947
• 负责人: NATHAN P STAFF
• 金额: $ 2.52万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6339947
• 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.

了解毒瘾的机制是现代神经生物学的一个主要目标。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区域，并且受到腹侧被盖多巴胺能末端的严重支配。最近，人们对海马 CA1 锥体神经元树突中的电压门控离子通道给予了很多关注，但很少有人关注其可能的重要性。在吸毒成瘾的情况下。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发生塑性变化。考虑到精神兴奋剂致敏后伏核神经元中神经元内在兴奋性的改变已被报道，这是一个特别令人感兴趣的现象。在该提案中，目标是了解树突固有电导的可塑性如何有助于毒瘾期间的神经适应。具体来说，我计划利用体外和体外药理学操作来探索 CA1 锥体树突功能的急性和慢性多巴胺能调节。