Electrophysiological ensembles organization during alcohol cue-induced intake and

描述（由申请人提供）：最喜欢的酒精饮料的味道、气味和视觉等环境刺激可能成为增加对酒精的渴望并导致个人继续饮酒直至醉酒（或远远超过）的明显线索。这些相同的线索也会导致长期戒酒的人的渴望和复发。由于持续过量饮酒和戒酒后复发都是酒精中毒的标志，因此了解调节线索诱发的酒精寻求的大脑区域和过程对于开发有效的治疗策略至关重要。 这些酗酒的人。有趣的是，大脑中一个被称为前额叶皮层（PFC）的区域内的神经活动现在被认为与调节酒精相关的线索如何引发渴望，酒精寻求和摄入有关。然而，介导持续过量饮酒和/或渴望和复发的神经活动的确切变化知之甚少。我们对具有酗酒遗传风险的人群如何在PFC中表现出异常的神经处理机制也只有非常有限的了解，这使得他们更容易受到与线索相关的渴望。我们假设，在PFC的神经网络将更强大的酒精配对线索的影响，在脆弱的人群比非脆弱。我们还假设，PFC神经元网络更耐重新映射在遗传易感人群戒酒期间。这些异常的神经元网络过程可能有助于提高线索诱发的渴望和驱动器都继续过量饮酒，以及戒酒后复发。我们广泛的，长期的目标是发展一个全面的了解如何神经网络（合奏）内的PFC改变酒精相关的线索。我们将通过使用最先进的电生理学记录和分析技术来完成这一点，该技术对清醒行为啮齿动物中的大量细胞进行记录和分析，以首次确定由酒精配对线索诱发的PFC集合活动的瞬时变化：1）有助于维持狂饮并在消退期间进行修改，以及2）启动复发样行为。我们将在具有过量饮酒遗传易感性的大鼠群体（印第安纳州酒精偏好P大鼠）和具有过量饮酒平均遗传易感性的大鼠群体（Wistar大鼠）中评价这些效应。确定过量饮酒的神经生物学/神经生理学原因和后果以及遗传易感性对过量饮酒的作用与NIAAA的使命直接相关。具体来说，拟议中的研究将揭示为什么遗传脆弱人群对酒精和酒精配对线索的反应不同的神经生物学起源。这将使我们更好地了解酒精为什么以及如何导致成瘾，并将帮助我们制定预防和治疗过度饮酒的策略。

DESCRIPTION (provided by applicant): Environmental stimuli such as the taste, smell, and sight, of a favorite alcoholic drink can become salient cues that increase craving for alcohol and lead individuals to continue to drink to the point of intoxication (or well beyond). These same cues can also cause craving and relapse in individuals who have abstained from alcohol for long periods of time. Because continued excessive alcohol intake and relapse following abstinence are both hallmarks of alcoholism, understanding the brain regions and processes that regulate cue-evoked alcohol seeking are critical to develop effective treatment strategies for these alcoholic individuals. Interestingly, neural activity within an area of the brain known as th prefrontal cortex (PFC) is now known to be critically involved in regulating how alcohol associated cues elicit craving, alcohol seeking, and intake. However, the exact changes in neural activity that mediate continued excessive alcohol intake and/or craving and relapse are poorly understood. We also have only a very limited understanding of how populations with genetic risk for developing alcoholism might exhibit abnormal neural processing regimes in the PFC, which make them more vulnerable to cue-related craving. We hypothesize that neural networks in the PFC will be more robustly effected by alcohol-paired cues in vulnerable populations than non-vulnerable. We also hypothesize that PFC neuronal networks are more resistant to re-mapping in genetically vulnerable populations during periods of abstinence from alcohol. These abnormal neuronal network processes might contribute to heightened cue-evoked craving and drive both continued excessive alcohol intake, as well as relapse following periods of abstinence. Our broad, long-term objective is to develop a comprehensive understanding of how neuronal networks (ensembles) within the PFC are altered by alcohol associated cues. We will accomplish this by using state-of-the-art electrophysiological recording and analysis techniques of large populations of cells in the awake behaving rodent to determine, for the first time, how instantaneous shifts in PFC ensemble activity evoked by alcohol paired cues: 1) contribute to the maintenance of binge- drinking and are modified during extinction, and 2) initiate relapse-like behavior. We will evaluate these effects in a rat population genetically predisposed to excessive alcohol consumption (Indiana alcohol preferring P rats) and in a rat population with average genetic susceptibility to excessive alcohol consumption (Wistar rats). Determining the neurobiological/neurophysiological causes and consequences of excessive alcohol consumption as well as the role of genetic vulnerability to excessive alcohol intake are directly relevant to the mission of the NIAAA. Specifically, the proposed studies will reveal the neurobiological origins of why genetically vulnerable populations respond to alcohol, and alcohol-paired cues, differently. This will lead us to a better understanding of why and how alcohol can cause addiction and will help us develop strategies to prevent and treat excessive drinking.