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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10659974
• 关键词: Address; Animals; Automobile Driving; Brain; Choice Behavior; Code; Collection; Consumption; Corpus striatum structure; Decision Making; Detection; Disease; Drug Addiction; Drug usage; Evaluation; Exhibits; Future; Hippocampus; Knock-in Mouse; Knowledge; Link; Measures; Mus; Neurons; Pattern; Physiological Processes; Population; Predictive Value; Process; Property; Public Health; Relapse; Rewards; Silicon; Site; Sleep; Synapses; Testing; Time; Update; Ventral Striatum; addiction; awake; cell type; drug relapse; in vivo; new therapeutic target; novel; optogenetics; reward processing; therapeutic target; therapeutically effective; transcriptomics

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，是一个重大的公共卫生负担。是 人们普遍认为，成瘾劫持了大脑中分配奖励的正常过程， 过去和未来的价值观。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 (VS)已被证明可以编码奖励值，但不知道这些值是如何产生的。 表示与特定的过去或未来动作相关联，或者功能表示如何与特定的过去或未来动作相关联， 奖励评估和预测的实现在不同的神经元之间被细分， 在这个建议中，我们通过研究相互作用来解决这些问题。 在VS和海马体（HPC）之间，它的主要输入之一。具体目标1： 测试HPC和VS之间的协调活动发生在 奖励收集涉及将奖励值链接到先前的动作并更新 大脑对奖励价值的估计。在具体目标2中，我们将检验假设 在奖励收集之前，HPC-VS的交互涉及在几个 基于其具有最高预测奖励值的可能动作。在具体目标3中，我们 将测试的假设，即在VS的神经元群体，与HPC之前或之后相互作用， 奖励收集是遗传上不同的神经元亚型。我们预计，该项目将 对我们了解大脑如何评估过去的奖励和预测未来做出了广泛的贡献 奖励，这可能会发现新的治疗药物成瘾的治疗目标。