Learning dependent neural encoding in the hippocampus

描述（由申请人提供）：长期目标是了解大脑如何学习和记忆。学习的目的是知情的行动：学到的事实和事件让我们利用过去来预测熟悉情况的结果。在学习过程中，如果过去的事件要提供信息并与正在进行的经验相关联，那么相关的记忆必须是可用的。这些能力需要海马体，在阿尔茨海默病中被破坏，但它们的神经元编码机制尚不清楚。在一个“类似情节”的记忆任务中，海马的活动随着最近的、正在进行的或即将发生的事件而变化，而行为的其他方面是相同的，揭示了当前的、前瞻性的或回顾性的编码。现在的目标是确定预测学习的放电模式。目的1将评估大鼠在熟悉的环境中学习新的空间行为时海马的编码。实验1将迫使大鼠在完成一个高度熟悉的、基于记忆的旅程之前，走新的或熟悉的弯路。因为旅程的起点和目标是不变的，所以即使绕道会导致不同的轨迹，熟悉的情节式记忆结构的编码也应该保持不变。依赖于密码的编码应该可以预测记忆表现和在新的弯路上的快速学习。实验2将在相同的环境中切换旅程的开始和目标。因此，老鼠必须在相同的空间环境中学习新的旅程。记忆性能和旅程依赖编码最初应该下降，和收购旅程依赖，编码应该预测在学习过程中的性能改善。目标2将评估海马编码，因为大鼠学习执行相同的记忆任务，但在一个新的，不熟悉的环境中，所以大鼠将不得不学习新的空间表征以及新的旅程。依赖性和独立性编码在学习初期应该是不存在的，但发展迅速，并且与旅程相关的编码的获得应该预测学习过程中的表现。目标3将测试即使在学习被阻止时，所识别的动态编码属性是否出现。将使用目标1和2中描述的相同行为方法，但将给予一组大鼠已知损害学习但不损害记忆表现的NMDA受体拮抗剂。强有力的预测是，稳定的记忆能力和伴随的海马编码都不会受到药物的影响，而目标1和2中伴随的学习和动态编码特性都将受损。每个目标将包括独立于校园的任务，这些任务需要相同的空间行为，但不需要记忆，并将评估人口和时间神经编码。这项研究应该为健忘症（例如中风或阿尔茨海默病）的合理治疗设计提供信息，包括神经假体的未来发展。

DESCRIPTION (provided by applicant): The long-term goal is to understand how the brain learns and remembers. The purpose of learning is informed action: learned facts and events let us use the past to anticipate the outcome of familiar situations. Relevant memories must be available during learning if past events are to inform and be associated with ongoing experience. These abilities require the hippocampus and are devastated in Alzheimer's disease, but their neuronal coding mechanisms are unknown. In an "episodic-like" memory task, hippocampal activity varied with recent, ongoing, or imminent events when other aspects of behavior were identical, revealing current, prospective, or retrospective coding. The aim now is to identify firing patterns that predict learning. Aim 1 will assess hippocampal coding as rats learn new spatial behaviors in a familiar environment. Experiment 1 will oblige rats to make either new or familiar detours before completing a highly familiar, memory-based journey. Because the start and goal of the journeys are unchanged, the same coding of the familiar episodic-like memory structure should be maintained even if detours entail different trajectories. Journey-dependent coding should predict memory performance and rapid learning in novel detours. Experiment 2 will switch the start and goal of journeys in the same environment. Thus the rats will have to learn new journeys in the same spatial environment. Memory performance and journey-dependent coding should decline initially, and the acquisition of journey-dependent, coding should predict performance improvement during learning. Aim 2 will assess hippocampal coding as rats learn to perform the same memory task but in a new, unfamiliar environment, so the rats will have to learn new spatial representations as well as a new journeys. Journey-dependent and independent coding should be absent initially, but develop rapidly, and the acquisition of journey-related coding should predict performance during learning. Aim 3 will test if the identified dynamic coding properties appear even when learning is blocked. The same behavioral methods described in Aims 1 and 2 will be used, but one group of rats will be given NMDA receptor antagonists known to impair learning but not memory performance. The strong prediction is that neither stable memory performance nor accompanying hippocampal coding will be affected by the drug, whereas both learning and the dynamic coding properties that accompany it in Aims 1 and 2 will be impaired. Each aim will include hippocampus-independent tasks that require the same spatial behaviors but not memory, and will assess both population and temporal neural coding. The research should inform the design of rational treatments for amnesia (e.g. by stroke or Alzheimer's disease), including the future development of neural prostheses.