Hippocampal interactions with striatal subnetworks for reward prediction and evaluation

项目摘要 吸毒成瘾是一种使人衰弱的疾病，是一个重大的公共卫生负担。它是 人们普遍认为，毒瘾劫持了大脑中分配奖励的正常过程 对过去和未来行动的价值。这些过程不被理解，这阻碍了我们的 识别有效治疗靶点的能力。大脑的腹侧纹状体的一部分 (VS)已被显示为对奖励值进行编码，但尚不清楚这些值是如何 表示与特定的过去或未来操作相关联，或者如何使用 奖赏评估和预测的实现在不同的神经元之间细分 VS中的细胞类型。在本提案中，我们通过研究交互作用来解决这些问题 在VS和其主要输入之一的海马体(HPC)之间。在具体目标1中，我们将 测试假设HPC和VS之间的协调活动发生在 奖赏收集涉及将奖励值链接到前一操作并更新 布莱恩对这笔赏金价值的估计。在具体目标2中，我们将检验这一假设 在奖励收集之前的HPC-VS交互参与在以下几个选择中 基于哪种可能的行动具有最高的预测奖励值。在具体目标3中，我们 将检验这样一种假设，即在VS中与HPC相互作用的神经元群体在之前或之后 奖赏收集是遗传上不同的神经元亚型。我们预计这个项目将 广泛帮助我们了解大脑如何评估过去的回报和预测未来 奖励，这可能为治疗药物成瘾确定新的治疗靶点。

Project Summary Drug addiction is a debilitating disorder that represents a significant public health burden. It is widely believed that addiction hijacks normal processes within the brain that assign reward values to past and future actions. These processes are not understood, which has hindered our ability to identify effective therapeutic targets. Part of the brain known as the ventral striatum (VS) has been shown to encode reward values, but it is not known how these value representations are linked to specific past or future actions, or how the functional implementations of reward evaluation and prediction are subdivided among different neuronal cell types within the VS. In this proposal, we address these questions by studying interactions between the VS and the hippocampus (HPC), one of its major inputs. In specific aim 1, we will test the hypothesis that coordinated activity between the HPC and the VS that occurs after reward collection is involved in linking the reward value to the previous action and updating the brain’s estimate of how valuable that reward was. In specific aim 2, we will test the hypothesis that HPC-VS interactions before reward collection are involved in choosing among several possible actions based on which has the highest predicted reward value. In specific aim 3, we will test the hypothesis that the neuronal populations in VS that interact with HPC before or after reward collection are genetically distinct neuronal subtypes. We expect this project will contribute broadly to our knowledge of how the brain evaluates past rewards and predicts future rewards, which may identify new therapeutic targets for treating drug addiction.