title: Critical role of the hippocampus in memory for elapsed time.
abstract: Episodic memory includes information about how long ago specific events occurred. Since most of our experiences have overlapping elements, remembering this temporal context is crucial for distinguishing individual episodes. The discovery of timing signals in hippocampal neurons, including evidence of "time cells" and of gradual changes in ensemble activity over long timescales, strongly suggests that the hippocampus is important for this capacity. However, behavioral evidence that the hippocampus is critical for the memory of elapsed time is lacking. This is possibly because previous studies have used time durations in the range of seconds when assessing hippocampal dependence, a timescale known to require corticostriatal circuits. Here we developed a nonspatial paradigm to test the hypothesis that the hippocampus is critical for keeping track of elapsed time over several minutes. We report that rats have a robust ability to remember durations at this timescale. We then determined the role of the hippocampus using infusions of fluorophore-conjugated muscimol, a GABAA agonist. We found that the hippocampus was essential for discriminating smaller, but not larger, temporal differences (measured in log units), consistent with a role in temporal pattern separation. Importantly, this effect was observed at long (minutes) but not short (seconds) timescales, suggesting an interplay of temporal resolution and timescale in determining hippocampal dependence. These results offer compelling evidence that the hippocampus plays a critical role in remembering how long ago events occurred.
authors: Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
authors: Nathan S
authors: NS
authors: Jacobs
authors: Timothy A
authors: TA
authors: Allen
authors: Natalie
authors: N
authors: Nguyen
authors: Norbert J
authors: NJ
authors: Fortin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D004192:Discrimination, Psychological / Q000187:drug effects; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D009812:Odorants; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D012903:Smell / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D058785:GABA-A Receptor Agonists; D009124:Muscle Proteins; C491788:Nol3 protein, rat; D009118:Muscimol
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