Cortico-striatal signaling in risk preference

描述（由申请人提供）：动物在遇到的几乎所有情况下都能灵活地从各种行为反应中进行选择。决策需要一个人从感官中收集信息，以确定适当的行为反应，同时考虑到备选方案可能带来的成本或回报。风险倾向和不适应的决策是许多精神疾病的特征，如药物成瘾和双相情感障碍，但也与赌博或过度借贷等常见行为有关。这一提议的目标是识别参与评估奖励和在确定和有风险的结果之间做出决定的神经结构的活动模式，这将告知风险偏好如何在单个神经元的活动中表现出来。老鼠将被训练去执行任务，在一个测试室中，它们在两个杠杆之间做出选择，这两个杠杆会导致不同的奖励结果（蔗糖颗粒）。在这些研究中，选择将基于不同的奖励大小或获得奖励的概率。当大鼠执行这些任务时，我们将记录伏隔核（NAC）中单个神经元的电生理活动，这对奖励处理至关重要，眶额皮质（OFC），一个被认为对基于奖励结果做出决定很重要的区域，以及前扣带皮层（ACC），这与监控冲突和风险有关。我们感兴趣的是这个回路是如何表示绝对奖励大小的信息的。“3个球”)到奖励的相对价值(例如：‘多于2’)。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征，从而导致对风险行为的高估。

DESCRIPTION (provided by applicant): Animals possess the flexibility to choose from a variety of behavioral responses in virtually every situation they encounter. Decision-making requires one to gather information from the senses to determine an appropriate behavioral response, taking into account the possible costs or rewards resulting from the alternatives. Risk-prone and maladaptive decision-making characterize a wide range of psychiatric disorders, such as drug addiction and bipolar disorder, but also pertain to such common behaviors as gambling or overextending one's credit. 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 tasks in which they choose between two levers in a test chamber that lead to different reward outcomes (sucrose pellets). In these studies, choices will be based on different reward magnitudes or probabilities of receiving reward. While rats perform these tasks we will record the electrophysiological activity of single neurons in the nucleus accumbens (NAC), which is critical for reward processing, orbitofrontal cortex (OFC), an area thought to be important for making decisions based on reward outcome, and anterior cingulate cortex (ACC), which has been implicated in monitoring conflict and risk. We are interested in how this circuit represents information about absolute reward size (e.g. '3 pellets') to relative value of reward useful for comparison (e.g. 'more than 2'). 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 how reward expectations- based on the magnitude of the reward and probability of receiving it- are represented in circuitry important for processing rewards and decision-making. These studies have the potential to identify mechanisms underlying risk-preference and therefore new targets for disorders of risky behavior.