Prospective memory coding by the hippocampus

海马体的前瞻性记忆编码

• 批准号: 7355971
• 负责人: Matthew L Shapiro
• 金额: $ 33.33万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355971
• 关键词: Alzheimer' s Disease; Amnesia; Animals; Behavior; Behavioral; Brain; Cells; Code; Cods; Cognitive; Consensus; Cues; Dependence; Development; Discrimination; Environment; Episodic memory; Event; Fire - disasters; Food; Functional RNA; Future; Goals; Habits; Hippocampal Formation; Hippocampus (Brain); Human; Hunger; Learning; Lesion; Location; Memory; Neurons; Neuropsychology; Outcome; Pattern; Performance; Physiology; Population; Process; Purpose; Pus; Rate; Rattus; Research; Research Personnel; Residual state; Rodent; Short-Term Memory; Signal Transduction; Specificity; Stimulus; Stroke; Structure; Task Performances; Testing; Thirst; Training; Upper arm; base; deprivation; design; episodic like memory; memory retrieval; neural prosthesis; novel; novel strategies; programs; prospective; prospective memory; relating to nervous system; research study; skills

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.

描述（由申请人提供）：长期目标是了解大脑是如何记忆的。记忆的最终目的是告知行动。我们回顾过去是为了预测熟悉情况的潜在结果。情景记忆需要海马体，并被阿尔茨海默病破坏，但海马体神经元如何准确地传达这种记忆尚不清楚。现在的目标是确定记忆所需的海马神经元活动模式。当大鼠执行海马体依赖的“情景式”记忆任务时，当其他方面的行为相同时，海马体神经元的放电模式随着即将发生或最近发生的事件而变化，分别揭示了前瞻性或回顾性编码。三个目标将系统地定性和定量地操纵海马体依赖的记忆需求：目标1将测试前瞻性和回顾性活动是否预测海马体依赖的空间记忆表现，而错误率通过干扰系统地变化。回顾性活动，尤其是前瞻性活动，应该预测持续记忆表现的变化。目的2将通过评估海马依赖性不同的两种非空间线索辨别任务中的神经元活动来检验目的1结果的普遍性。大鼠将执行与目标1相同的行为：一项任务不受海马损伤的影响，另一项应该受损。记忆需求和错误率会随着刺激呈现的延迟和模式的改变而改变。如果海马神经元主动募集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，并随着错误的发生而减少；如果没有这些要求，这种活动应该是最小的，并且与错误无关。目的3将评估在执行一项新的非空间任务时的编码，该任务需要海马体和灵活的记忆检索，但不需要最近的记忆。训练大鼠根据其剥夺状态（饥饿或口渴）接近不同的非空间目标物体，海马损伤后受到损害。如果前瞻性编码反映了海马体独立于近期记忆发出即将发生事件信号的一般计算过程，那么神经元活动应该预测选择和预测错误。每个目标将评估人口和时间编码及其相互作用。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。