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：
7470832
负责人：
Stephen N. Gomperts
金额：
$ 17.06万
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/7470832
关键词：
Animals Area Behavior Behavioral Brain Brain region Cells Choice Behavior Clinical Code Communities Condition Data Dopamine Dopamine Antagonists Drug Addiction Episodic memory Future GBR 12935 General Hospitals Goals Hippocampus (Brain)Lead Learning Location Maps Massachusetts Memory Disorders Midbrain structure Modeling Movement Neurons Neurosciences Opiates Output Parkinson Disease Performance Personal Satisfaction Phase Play Prefrontal Cortex Property Psychological reinforcement Range 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）：该提案旨在探索腹侧对盖区域（VTA）中神经元活动的结构及其与增强空间学习过程中海马（HC）中神经元活性的关系。 VTA多巴胺（DA）系统是强化学习的关键基础，似乎是动物用于选择目标的内部价值图。 HC还可以在增强的空间学习中起作用，因为这对于导航和情节记忆是必要的。在自由移动的动物中，在空间域中，VTA活动可能会促进目标导航。 VTA GABA神经元可能在指导和调节价值编码方面起关键作用。它们投射到与包括HC在内的DA细胞相同的结构，并抑制DA神经元。在局部，VTA GABA神经元可以参与奖励预测误差（RPE）的DA细胞计算，并可能调节DA细胞输出。通过他们的预测，GABA神经元还可以动态选择DA信号的目标结构，并可能为它们提供与DA无关的奖励相关信息。这项研究将采用VTA和HC中神经元集合的多电极记录，通过3个特定目标阐明其相互作用。首先，它将评估VTA DA和GABA神经元代表预测未来奖励的轨迹的能力。然后，它将探索GABA神经元活性在RPE表示中的作用。最后，它将在正常条件下以及在DA功能的药理扰动下进行增强空间学习中的VTA-HC相互作用。候选人的直接目的是获得由Matthew Wilson博士赞助的醒着大鼠的VTA和HC中多电极记录的培训，并由John Growdon博士赞助了运动和记忆障碍的互补临床培训。因此，哈佛大学和马萨诸塞州综合医院的实验室和麻省理工学院神经科学社区的许多资源将得到增强。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系统在增强学习，认知控制，帕金森氏病，药物成瘾和精神分裂症中的关键作用，以及HC在情节记忆，空间导航和精神分裂症中的重要性，因此对VTA功能以及与HC诸如HC诸如HC相关的大脑方面的机制洞悉。