Revealing the causal role of hippocampal dopamine signaling in spatial learning

揭示海马多巴胺信号在空间学习中的因果作用

基本信息

批准号：
8903494
负责人：
Jonathan Newman
金额：
$ 5.24万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8903494
关键词：
Affect Agreement Amnesia Anterior Area Back Behavior Behavioral Biological Preservation Brain Brain Injuries Cells Clinical Control Animal Detection Development Dopamine Electrophysiology (science)Epilepsy Event Excision Experimental Designs Exploratory Behavior Future Hippocampal Formation Hippocampus (Brain)Individual Infarction Laboratories Lateral Learning Link Location Long-Term Potentiation Maintenance Medial Memory Methods Neurodegenerative Disorders Neurosciences Research Non-Insulin-Dependent Diabetes Mellitus Nucleus Accumbens Patients Performance Phase Physiological Play Positioning Attribute Prefrontal Cortex Process Prosthesis Radial Rattus Research Retrograde amnesia Rewards Role Sampling Short-Term Memory Signal Transduction Source Stimulus System Temporal Lobe Testing Theta Rhythm Training Traumatic Brain Injury Ventral Tegmental Area Wakefulness Work age related arm base dopaminergic neuron experience in vivo interest long term memory memory acquisition memory consolidation memory trace reactivation neural patterning optogenetics place fields public health relevance relating to nervous system research study spatial memory success tool

项目摘要

DESCRIPTION (provided by applicant): Damage to the hippocampal formation results in loss of recent memory and an inability to form and maintain new long-term memories. Consequently, there is agreement that the hippocampal formation plays a crucial role in memory consolidation, the process by which `labile' memory traces are transferred from hippocampal networks to permanent cortical storage over weeks or months. Understanding the mechanisms by which motivationally- salient memory traces are selected for consolidation is a major objective of systems-level neuroscience research. Dopamine (DA) is required for the maintenance of long-term potentiation in hippocampal networks. Disruption of ventral tegmental area (VTA) DA signaling to hippocampus leads to deficits in long-term memory formation. The VTA is also the primary source of DAergic projections to brain areas that serve important motivational roles, such as the nucleus accumbens and medial prefrontal cortex. For these reasons, it has been widely postulated that VTA DA signaling may serve as a `salience tag' for important hippocampus-dependent memories, designating them from long-term storage. Recent work from our lab has revealed distinct forms of VTA-hippocampal activity coordination during active spatial exploration compared to hippocampal `replay' of previous experience that occurs during quiet-wakefulness. This suggests that the role of VTA DA signaling in spatial learning may be switched rapidly depending on behavioral and/or neural state. However, a causal role for VTA-hippocampal activity coordination in spatial memory has not yet been established. In the work proposed here, VTA DA neurons will be optogenetically suppressed contingent on either active exploratory behavior or the detection of memory trace reactivation during quiet wakefulness. This closed-loop approach will allow selective, state-dependent disruption of VTA-hippocampal coordination. Consequent effects on spatial learning can then be directly attributed to the presence or absence of DA signaling during active exploration or mentation of previous experience. The intense scientific interest in understanding the mechanistic basis of memory consolidation is a result of its far-reaching clinical implications. Damage to the hippocampal formation can occur for a number of reasons including traumatic brain injury, type 2 diabetes, resection of epileptic foci, hippocampal infarct, and primary age- related neurodegenerative diseases. Hippocampal damage often results in temporally-graded retrograded amnesia and an inability to form new declarative memories. Better understanding the mechanisms by which the hippocampus is able to selectively gate important memories to long-term storage will inform the development of prosthetic devices to rescue memory function in individuals with hippocampal damage.

海马形成的损害会导致最近和inado形式的丧失，并保持新的术语记忆。在几周内，选择了积极的记忆痕迹以进行整合，这是系统级神经的主要目标。长期记忆形成也是对大脑区域的主要来源 - 依赖性的记忆，从我们实验室的长期存储中指定它们，揭示了在竞技表演中，在Qiet-wakefuls中，在竞技上均采用了vta-Hippocampal坐标协调的形式。但是，神经状态。 - 在记忆巩固的机理基础上，高度的科学兴趣是一种有远见的临床意义。大门的长期存储的重要记忆将使海马损害的人的假体装置记忆功能的发展。