Hippocampal interactions with striatal subnetworks for reward prediction and evaluation

海马与纹状体子网络的相互作用用于奖励预测和评估

基本信息

批准号：
10659974
负责人：
Lucas L Sjulson
金额：
$ 47.41万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2028-06-30
项目状态：
未结题

项目摘要

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.

项目摘要吸毒成瘾是一种使人衰弱的疾病，代表着重要的公共卫生伯恩。这是广泛认为成瘾劫持了大脑中的正常过程，以分配奖励过去和将来的行动的价值观。这些过程尚不理解，这阻碍了我们能够识别有效的治疗靶标。大脑的一部分被称为腹纹状体（vs）已被证明是编码奖励值，但尚不知道这些值如何表示形式与特定的过去或将来的行动有关，或者如何功能奖励评估和预测的实施被细分在不同的神经元之间 VS中的细胞类型在此提案中，我们通过研究互动来解决这些问题在VS和海马（HPC）之间，这是其主要输入之一。在特定目标1中，我们将检验以下假设，即HPC和VS之间的协调活性奖励收集参与将奖励价值与以前的操作联系起来并更新大脑对该奖励有多有价值的估计。在特定目标2中，我们将检验假设奖励收集之前的HPC-VS交互参与了几种基于哪些具有最高预测奖励价值的行动。在特定的目标3中，我们将检验以下假设：在与HPC相互作用之前或之后与HPC相互作用的神经元种群奖励收集是遗传上不同的神经元亚型。我们希望这个项目将广泛地为我们了解大脑如何评估过去的奖励和预测未来的知识奖励，这可能确定用于治疗吸毒成瘾的新治疗靶标。