Prospective memory coding by the hippocampus

描述(由申请人提供)：长期目标是了解大脑是如何记忆的。记忆的最终目的是知情的行动。我们回顾过去，以预测熟悉情况的潜在结果。情节记忆需要海马体，并被阿尔茨海默病摧毁，但海马神经元确切地如何通知这种记忆尚不清楚。现在的目标是确定记忆所需的海马神经元活动模式。当大鼠执行海马区依赖的“情景式”记忆任务时，当其他行为方面相同时，海马神经元的放电模式随着即将发生的或最近发生的事件而变化，分别显示出前瞻性或回溯性编码。三个目标将定性和定量地系统地操纵海马体依赖的记忆需求：目标1将测试前瞻性和回溯性活动是否预测海马体依赖的空间记忆表现，而错误率通过干扰而系统地变化。回溯性的，尤其是前瞻性的活动应该预测正在进行的记忆性能的变化。目标2将通过评估两个在海马体依赖方面不同的非空间线索辨别任务中的神经元活动来测试目标1的结果的一般性。大鼠将执行与目标1相同的行为：一个任务不受海马区损伤的影响，另一个任务应该受到损害。内存需求和错误率将通过改变刺激呈现的延迟和模式来改变。如果海马神经元主动招募记忆编码需要特定的记忆需求，那么记忆编码应该随着这些需求的增加而增加，随着错误的出现而减少；如果没有这些需求，这种活动应该是最小的，并且与错误无关。目标3将评估在执行一项新的非空间任务时的编码情况，该任务需要海马体和灵活的记忆提取，但不需要最近的记忆。被训练为接近不同非空间目标对象的大鼠，取决于它们的剥夺状态(饥饿或口渴)，在海马区损伤后受损。如果预期编码反映了一个一般的计算过程，通过这个过程，海马体发出即将发生的事件的信号，而不依赖于最近的记忆，那么神经元活动应该预测选择和预测错误。每个目标都将评估人口和时间编码及其相互作用。这项研究应该为健忘症(例如中风或阿尔茨海默病)的合理治疗方案的设计提供信息，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 remembers. Memory's ultimate purpose is informed action. We recall the past to anticipate potential outcomes of familiar situations. Episodic memory requires the hippocampus and is devastated by Alzheimer's disease, yet precisely how hippocampal neurons inform such memory is unknown. The aim now is to identify patterns of hippocampal neuronal activity required for memory. As rats performed a hippocampus-dependent "episodic-like" memory task, the firing patterns of hippocampal neurons varied with imminent or recent events when other aspects of behavior were identical, revealing prospective or retrospective coding, respectively. Three Aims will systematically manipulate hippocampus-dependent memory demand qualitatively and quantitatively: Aim 1 will test if prospective and retrospective activities predict hippocampus-dependent spatial memory performance while error rate is varied systematically via interference. Retrospective and especially prospective activity should predict changes in ongoing memory performance. Aim 2 will test the generality of the results in Aim 1 by assessing neuronal activity in two non-spatial cue discrimination tasks that differ in hippocampus dependence. Rats will perform the same behaviors as in Aim 1: one task is unaffected by hippocampal lesions, the other should be impaired. Memory demand and error rates will be varied by altering the delay and pattern of stimulus presentation. If the active recruitment of memory coding by hippocampal neurons requires specific memory demands, then memory coding should increase as those demands increase and decline with errors; without those demands, such activity should be minimal and unrelated to errors. Aim 3 will assess coding during performance of a novel non-spatial task that requires the hippocampus and flexible memory retrieval, but not recent memory. Rats trained to approach different non-spatial goal objects depending on their deprivation state (hunger or thirst) were impaired after hippocampal lesions. If prospective coding reflects a general computational process by which the hippocampus signals impending events independent of recent memory, then neuronal activity should anticipate choice selection and predict errors. Each aim will assess population and temporal coding and their interaction. 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.