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. ? ?
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