Ethanol and Neurophysiology of the Mesolimbic System

描述(由申请人提供)：中边缘区域，包括 内侧和外侧前额叶皮质、伏隔核和腹侧 被盖区(VTA)被认为是调节神经信号的媒介 追求报酬的行为。这个研究项目将学习神经生理学。 酒精对小鼠奖赏和学习功能的影响 中边缘系统。同步记录穗序列的先进方法 不同中缘区大规模神经元群体的活动 将应用跨天的多个会话来获取有关 与乙醇在不同时间尺度上的作用有关的电路功能。一个 最初的目的是确定中边缘系统变化的进展情况。 大鼠在获得乙醇自我给药的所有阶段 从高百分比蔗糖到高百分比乙醇的褪色过程 集中精神。将正常的Long Evans大鼠与近交系P (偏爱酒精的)大鼠将从乙醇研究中心获得 在印第安纳大学。第二个目标是将反应的变化描述为语调提示 有条件地提供有关将在 喷嘴。第三个目标将研究中脑边缘区域的神经元活动。 操作反应模式递进比率鼻戳对乙醇的反应 在灭绝期间表现出持续反应的P鼠中，以及 在酒精剥夺效应中的反应增强。我们假设 伏隔核将显示最不同的反应 以中枢整合为特征；眼眶额叶皮质将调节 品味和回报评估中介未来的行为选择 前额叶皮质将表现出对反应选择和VTA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。一个 统一的概念是乙醇将通过诱导产生广泛的影响 不能灵活地控制对奖励作出反应的条件线索 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.