Dopaminergic modulation of CA1 intrinsic excitability

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，受腹侧被盖多巴胺能末梢的大量神经支配。近年来，人们对海马CA1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，CA1神经元中的电压门控离子通道可以在突触条件反射后发生可塑性变化。这是一个特别有趣的现象，因为在精神兴奋剂致敏后，伏隔核神经元的内在兴奋性发生了变化。在这个提议的目标是了解树突内在传导的可塑性如何有助于药物成瘾期间看到的神经适应。具体来说，我计划通过体外和体外药理操作来探索急性和慢性多巴胺能调节CA1锥体树突功能。

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.