Dopaminergic modulation of CA1 intrinsic excitability

CA1 内在兴奋性的多巴胺能调节

• 批准号: 6719028
• 负责人: Nathan P Staff
• 金额: $ 0.9万
• 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 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719028
• 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梢的严重神经支配。近年来，海马CA1区锥体神经元树突上的电压门控离子通道受到了广泛的关注，但很少有人关注它的重要性。吸毒成瘾。我的初步证据表明，CA1神经元中的电压门控离子通道在突触条件反射后可以发生可塑性变化。这是一个特别令人感兴趣的现象，因为已经报道了在精神兴奋剂致敏后在延髓核神经元中神经元的内在兴奋性的改变。在这个提议中，目标是了解树突固有电导的可塑性如何有助于药物成瘾期间的神经适应。具体来说，我计划探索急性和慢性多巴胺能调制CA1锥体树突功能，在体外和体外药理学操作。