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：所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，如果要将过去的事件与正在进行的经验联系起来，就必须有相关的记忆。这些能力需要海马体，并在阿尔茨海默病中被破坏，但其神经元编码机制尚不清楚。在“情景式”记忆任务中，当行为的其他方面相同时，海马体活动随着最近的、正在进行的或即将发生的事件而变化，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的海马编码。实验1将要求老鼠在完成一个非常熟悉的、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，即使弯路需要不同的轨迹，熟悉的类情景记忆结构的编码也应该保持不变。旅程依赖编码应该预测记忆性能和快速学习的新弯路。实验2将在相同的环境中切换旅程的起点和目标。因此，老鼠将不得不在相同的空间环境中学习新的旅程。记忆表现和路程依赖编码在学习初期会下降，而路程依赖编码的习得可以预测学习过程中表现的提高。目标2将评估当大鼠在一个新的、不熟悉的环境中学习执行相同的记忆任务时，海马体编码，所以大鼠必须学习新的空间表征以及新的旅程。旅程相关编码和独立编码最初应该不存在，但会迅速发展，并且与旅程相关编码的习得可以预测学习过程中的表现。目标3将测试即使在学习受阻时，识别的动态编码属性是否出现。将使用目标1和目标2中描述的相同的行为方法，但一组大鼠将被给予已知会损害学习但不会损害记忆表现的NMDA受体拮抗剂。强有力的预测是，稳定的记忆表现和伴随的海马体编码都不会受到药物的影响，而在目标1和目标2中伴随的学习和动态编码特性将受到损害。每个目标都将包括与海马体无关的任务，这些任务需要相同的空间行为，但不需要记忆，并将评估群体和时间神经编码。这项研究应该为设计合理的失忆症治疗方法（例如中风或阿尔茨海默病）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.