Integrating Hippocampus, Ventral Striatum, and Prefrontal Cortex during Deliberative Decision Making

 描述（由申请人提供）：成瘾的决策是如何出错的？ 决策过程已在人类、灵长类动物和啮齿动物中得到广泛研究。然而，我们仍然没有完全理解支持决策的神经生理过程。为了回答决策是如何出错的，我们必须首先问我们是如何做出决策的。适应不良的决策可能是由于一个或多个决策系统中的处理错误或不同决策系统之间的冲突造成的。因此，我们需要建立一个更好的理解机制的审议决策，以了解神经的原因适应不良的决策。我建议利用一种新的病毒技术（DREADD）来研究三个神经系统如何在审慎决策过程中整合信息。我建议研究腹侧纹状体如何评估奖励，海马如何想象未来，前额叶皮层如何偏向海马的上下文表示，最后这三个系统如何相互作用/偏见在审议决策。 我建议同时记录神经元合奏和当地的场电位从前额叶皮层，海马和腹侧纹状体的大鼠训练的空间神经经济任务（餐厅行）。在餐馆行任务中，在可变的随机延迟后，向大鼠提供不同食物奖励的选项。老鼠可以选择等待食物奖励的延迟，或者跳过选择并移动到下一个奖励地点。将大型合奏记录与复杂的计算分析相结合，使我们能够以令人难以置信的快速时间尺度（毫秒与分钟和小时）测量神经过程。通过这样做，我们可以更好地分析时间尺度上的神经过程，更类似于在决策过程中观察到的表征信息处理的时间特异性（约翰逊等人，2009年）。因此，我们可以从具体的神经生物学过程中推断抽象的认知过程，如决策过程。 本提案旨在审查三个问题：1）在决策过程中，前额叶皮层沉默对动态搜索和评估过程（VTE）的行为相关性有什么影响，2）PFC和预测/计划的海马空间表征和/或腹侧纹状体对奖励的隐蔽期望之间是否存在因果关系，3）前额叶皮层沉默是否会损害离线协调的大脑皮层-腹侧纹状体位置-奖励再激活（重放）。通过回答这些问题，我们将更好地理解这些不同的神经系统在深思熟虑的决策过程中是如何相互作用的，并更接近回答这个问题：成瘾的决策是如何出错的？

 DESCRIPTION (provided by applicant): How does decision making go awry in addiction? Decision making processes have been extensively studied in humans, primates, and rodents. However, we still do not fully understand the neurophysiological processes supporting decision making. In order to answer how decision making goes awry, we must first ask how we make decisions. Maladaptive decision making could result from an error in processing in one or several decision making systems or a conflict between different decision making systems. Consequently, we need to establish a better understanding of the mechanisms of deliberative decision making in order to understand the neurological causes of maladaptive decision making. I propose to utilize a novel viral technology (DREADD) to examine how three neural systems integrate information during deliberative decision making. I propose to examine how the ventral striatum evaluates reward, how the hippocampus imagines the future, how the prefrontal cortex biases hippocampal representations of context, and finally how these three systems interact/bias each other during deliberative decision making. I propose to simultaneously record neuronal ensembles and local field potentials from the prefrontal cortex, hippocampus and ventral striatum in rats trained on a spatial neuroeconomic task (Restaurant Row). On the Restaurant Row task rats are presented with the option of different food rewards dispensed after variable random delays. The rats have the choice of waiting out the delay for the food reward or skipping the choice and moving on to the next reward site. Combining large ensemble recordings with sophisticated computational analyses permits us to measure neural processes at incredibly fast time-scales (ms vs. minutes and hours). By doing so we can better analyze neural processes at time-scales more analogous to the temporal specificity that characterizes information processing seen during decision-making (Johnson et al., 2009). Therefore, we can extrapolate abstract cognitive processes, such as decision-making, from concrete neurobiological processes. This proposal aims to examine three questions: 1) what are the effects of silencing the prefrontal cortex on behavioral correlates of the dynamic search and evaluation processes (VTE) seen during decision-making, 2) is there a causal relationship between PFC and hippocampal spatial representations of prediction/planning and/or ventral striatum covert expectations of reward, 3) does silencing the prefrontal cortex impair off-line coordinated hippocampal-ventral striatal place-reward reactivation (replay). By answering these questions we will have a better understanding of how these disparate neural systems interact during deliberative decision making and get closer to answer the question: how does decision making go awry in addiction?