Neural Basis of Decisions about Uncertain Rewards

描述(由申请人提供)：愿意从事危险行为是吸毒、赌博和肥胖的标志。想必，一个人选择服用违禁药物、过量食用一顿高脂肪食物或将1000美元押在红色上，是因为这种选择的直接结果可能是有回报的。这项提议的目标是确定神经结构中的活动模式，这些结构涉及评估奖励和在某些结果和风险结果之间做出决定，这将告知风险偏好如何在单个神经元的活动中表现出来。老鼠将被训练来执行一项风险任务，在这项任务中，它们在试验室中的两个杠杆之间进行选择，这两个杠杆会导致不同的奖励结果(蔗糖丸)。按下确定的杠杆总是会得到很小的回报，而按下不确定的杠杆要么会得到很大的回报，要么会忽略奖励。大的或省略的奖励结果是随机选择的，这样受试者就不能跟踪大的结果的数量，从而最大化整个试验的总回报。在强迫反应块中，每个杠杆将在交替试验中单独呈现，这为大鼠提供了平等地采样两种行为选项及其相关后果的机会。这之后是一个自由选择块，其中两个杠杆同时出现，大鼠能够选择一个。对选择的分析将集中在不同阶段的风险偏好以及奖励历史对即将到来的选择的影响。当大鼠执行风险任务时，我们将记录伏隔核(NAC)和眼眶额叶皮质(OFC)中单个神经元的电生理活动，这两个区域对奖励处理至关重要，被认为是根据奖励结果做出决定的重要区域。在NAC和OFC，我们将衡量在奖励交付或遗漏之前、期间和之后发生的事件的反应。神经活动的水平将通过两种行为反应(确定-不确定)进行比较，无论是否自由选择，并与三种可能的结果(小、大、省略)进行比较。我们研究的长期目标是确定这些区域的异常信号如何可能导致对奖励的不准确表示，进而可能导致对危险行为的高估。与公共健康相关：与吸毒、赌博或过度消费(食物或商品)相关的普遍问题源于愿意从事产生危险结果的行为。这个项目的目标是识别神经结构中的活动模式，这些结构涉及评估奖励和做出具有风险后果的选择的决策，这将告知风险偏好如何在单个神经元的活动中表现出来。这些研究有可能确定风险倾向行为的机制，从而为其治疗提供新的靶点。

DESCRIPTION (provided by applicant): The willingness to engage in risky behaviors is hallmark of drug addiction, gambling, and obesity. Presumably, one chooses to administer an illicit drug, over-consume a fat-laden meal, or put $1000 on red because the immediate outcome of the choice is potentially rewarding. The goal of this proposal is to identify patterns of activity in neural structures involved in evaluating rewards and making decisions between certain and risky outcomes that will inform how risk-preference is represented in the activity of single neurons. Rats will be trained to perform a Risk task, in which they choose between two levers in a test chamber that lead to different reward outcomes (sucrose pellets). Pressing the Certain lever always earns a Small reward, and pressing the Uncertain lever will either pay a Large reward or Omit the reward. Large or Omitted reward outcome is chosen randomly, so that subjects cannot track the number of Large outcomes to maximize overall payoffs across trials. In a forced response block, each lever will be presented alone on alternate trials, which provides the opportunity for the rat to equally sample both behavioral options and their associated consequences. This is followed by a free choice block, in which both levers are presented simultaneously and rats are able to select one. Analyses of choices will focus on risk-preference across sessions and the influence of reward-history on upcoming choices. While rats perform the Risk task we will record the electrophysiological activity of single neurons in the Nucleus Accumbens (NAc), which is critical for reward processing and in the Orbitofrontal cortex (OFC), an area thought to be important for making decisions based on reward outcome. In both NAc and OFC, we will measure responses to events leading up to, during, and following reward delivery or omission. The level of neural activity will be compared across the two behavioral responses (Certain-Uncertain), when freely chosen or not, and to the three possible outcomes (Small, Large, Omit). The long-term goal of our studies is to determine how aberrant signaling in these areas may underlie inaccurate representations of reward which may in turn lead to over-valuation of risky behaviors. PUBLIC HEALTH RELEVANCE: The pervasive problems associated with drug addiction, gambling, or overconsumption (of food or goods) stem from a willingness to engage in behaviors that yield risky outcomes. The goal of this project is to identify patterns of activity in neural structures involved in evaluating rewards and making decisions about choices with risky consequences that will inform how risk-preference is represented in the activity of single neurons. These studies have the potential to identify mechanisms of risk-prone behaviors and therefore new targets for their treatment.