Ethanol and Neurophysiology of the Mesolimbic System

描述（由申请人提供）：中脑边缘区，包括 内侧和外侧前额叶皮质、前额叶核和腹侧 被盖区（VTA）被认为是介导调节神经信号， 寻求奖励的行为。这项研究计划将研究神经生理学 乙醇对大脑皮层的奖励和学习功能的影响 中脑边缘系统同步记录棘波序列的先进方法 不同中脑边缘区大规模神经元群的活动 在许多会议跨越天将适用于获得信息的 与乙醇在不同时间尺度上的作用相关的电路功能。一个 最初的目的是确定在中脑边缘系统的变化的进展， 大鼠在获得乙醇自我管理的所有阶段， 从高百分比蔗糖到高百分比乙醇的褪色过程 浓度.将正常Long Evans大鼠与近交系P 从乙醇研究中心获得的（乙醇偏好）大鼠 在联合印第安纳州。第二个目标是将反应的变化描述为音调提示 条件是提供有关奖励的信息，以获得 喷。第三个目标是研究大脑皮层中脑边缘区的神经元活动。 操作性反应模式进行性比率对乙醇的反应 在P大鼠中，在灭绝过程中表现出持续反应， 在酒精去瘾效应期间增强反应。我们假设 脑桥核会显示出最不均匀的反应 中央整合的特征;眶额叶皮层将介导 品味和奖励评价测试介导未来行为选择选择，中介 前额叶皮层将表现出反应选择的神经编码， 多巴胺神经元将跟踪预测未来奖励的线索信息。一 一个统一的概念是，乙醇将通过诱导产生广泛的影响， 对条件线索反应的控制能力 寻求行为。

DESCRIPTION (provided by applicant): The mesolimbic regions including the medial and lateral prefrontal cortices, the nucleus accumbens, and ventral tegmental area (VTA) are thought to mediate the neural signals that regulate reward-seeking behaviors. This research program will study the neurophysiology of the influence of ethanol on the reward and learning functions of the mesolimbic system. Advanced methods for simultaneous recording of spike train activity of large scale populations of neurons in different mesolimbic regions over many sessions across days will be applied to obtain information on the circuit functions related to actions of ethanol over different time scales. An initial aim is to determine the progress of changes in the mesolimbic system in rats at all stages of acquisition of self-administration of ethanol by a procedure of fading from a high percent sucrose to a high percent ethanol concentration. Normal Long Evans rats will be compared with the inbred P (ethanol-preferring) rats to be obtained from the Center for Ethanol Research at U. Indiana. A second aim will characterize change in responses as tone cues are conditioned to provide information about the reward to be obtained at a spout. A third aim will study neuronal activity in mesolimbic regions on the pattern of operant responses progressive ratio nose poke responding for ethanol in the P rats that exhibit persistent responding during extinction, and enhanced responding during the Alcohol Deprivation Effect. We hypothesize that the nucleus accumbens will reveal the most heterogeneous responses characteristic of central integration; orbital frontal cortex will mediate taste and reward valuation t mediate future behavioral choice selection, medial prefrontal cortex will exhibit neural coding of response selection and that VTA dopamine neurons will track information of cues predictive of future reward. A unifying concept is that ethanol will exert widespread influences by induction of an inflexibility of control over conditioned cue responding for reward seeking behavior.