Ventral Tegmental Area and Hippocampal Interactions in Reinforced Spatial Learnin

强化空间学习中的腹侧被盖区和海马相互作用

基本信息

批准号：
8078180
负责人：
Stephen N. Gomperts
金额：
$ 18.09万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8078180
关键词：
Animals Area Behavior Behavioral Brain Brain region Cells Choice Behavior Clinical Code Communities Data Dopamine Dopamine Antagonists Drug Addiction Episodic memory Future General Hospitals Goals Hippocampus (Brain)Lead Learning Location Maps Massachusetts Memory Disorders Midbrain structure Modeling Movement Disorders Neurons Neurosciences Opiates Output Parkinson Disease Performance Phase Play Prefrontal Cortex Property Psychological reinforcement Rattus Resources Rewards Role Route Schizophrenia Self Administration Self Stimulation Shapes Short-Term Memory Signal Transduction Site Stimulus Structure Theta Rhythm Training Uncertainty Universities Ventral Tegmental Area Work awake base clinically relevant cognitive control conditioning dopamine system dopamine transporter dopaminergic neuron experience gamma-Aminobutyric Acid inhibitor/antagonist insight prevent response tool way finding

项目摘要

DESCRIPTION (provided by applicant): This proposal seeks to explore the structure of neuronal activity in the ventral tegmental area (VTA) and its relationship with neuronal activity in the hippocampus (HC) during reinforced spatial learning. The VTA dopamine (DA) system is a key substrate of reinforcement learning that appears to underlie the internal map of value that animals use to select goals. The HC also functions in reinforced spatial learning, as it is necessary for navigation and episodic memory. In freely moving animals, in the spatial domain, VTA activity may additionally contribute to navigation towards goals. VTA GABA neurons may play a critical role in directing and regulating the encoding of value. They project to the same structures as DA cells, including the HC, and inhibit DA neurons. Locally, VTA GABA neurons may participate in the DA cell computation of reward prediction error (RPE) and may regulate DA cell output. Through their projections, GABA neurons may also dynamically select target structures for DA signaling and may provide them with DA-independent reward-related information. This study will employ multielectrode recordings of neuronal ensembles in the VTA and HC to elucidate their interactions through 3 specific aims. First, it will assess the capacity for VTA DA and GABA neurons to represent trajectories predictive of future reward. Then, it will explore the role of GABA neuronal activity in the RPE representation. Lastly, it will examine VTA-HC interactions in reinforced spatial learning in normal conditions and after pharmacological perturbations of DA function. The immediate goal of the candidate is to obtain training in multielectrode recording in the VTA and HC of awake behaving rats, sponsored by Dr. Matthew Wilson, with complementary clinical training in movement and memory disorders, sponsored by Dr. John Growdon. The many resources of the lab and MIT neuroscience community will thus be enhanced by those of Harvard University and Massachusetts General Hospital. The long- term goal is to learn how the VTA contributes to normal and aberrant cognitive control, through its intrinsic circuitry and interactions with other brain regions. Given the pivotal role of the DA system in reinforcement learning, cognitive control, Parkinson's disease, drug addiction, and schizophrenia, and the importance of the HC in episodic memory, spatial navigation, and schizophrenia, insights into VTA function and the mechanisms by which it communicates with brain areas such as the HC will have high clinical relevance.

描述（由申请人提供）：本提案旨在探索强化空间学习过程中腹侧被盖区（VTA）神经元活动的结构及其与海马（HC）神经元活动的关系。 VTA 多巴胺 (DA) 系统是强化学习的关键基础，它似乎是动物用来选择目标的内部价值图的基础。 HC 还具有强化空间学习的功能，因为它是导航和情景记忆所必需的。在自由活动的动物中，在空间域中，VTA 活动可能还有助于导航至目标。 VTA GABA 神经元可能在指导和调节价值编码中发挥关键作用。它们投射到与 DA 细胞相同的结构，包括 HC，并抑制 DA 神经元。在局部，VTA GABA 神经元可能参与 DA 细胞奖励预测误差 (RPE) 的计算，并可能调节 DA 细胞的输出。通过它们的预测，GABA 神经元还可以动态地选择 DA 信号传导的目标结构，并可以为它们提供与 DA 无关的奖励相关信息。这项研究将采用多电极记录 VTA 和 HC 中的神经元群，通过 3 个特定目标来阐明它们之间的相互作用。首先，它将评估 VTA DA 和 GABA 神经元代表预测未来奖励轨迹的能力。然后，它将探讨 GABA 神经元活动在 RPE 表征中的作用。最后，它将检查正常条件下以及 DA 功能药理学扰动后 VTA-HC 在强化空间学习中的相互作用。候选人的近期目标是获得由 Matthew Wilson 博士赞助的清醒行为大鼠 VTA 和 HC 多电极记录培训，以及由 John Growdon 博士赞助的运动和记忆障碍方面的补充临床培训。因此，哈佛大学和马萨诸塞州总医院的资源将增强实验室和麻省理工学院神经科学界的许多资源。长期目标是了解 VTA 如何通过其内在电路以及与其他大脑区域的相互作用来促进正常和异常的认知控制。鉴于 DA 系统在强化学习、认知控制、帕金森病、药物成瘾和精神分裂症中的关键作用，以及 HC 在情景记忆、空间导航和精神分裂症中的重要性，深入了解 VTA 功能及其机制与 HC 等大脑区域进行通信将具有高度的临床相关性。