title: Cognitive impairment in temporal lobe epilepsy: role of online and offline processing of single cell information.
abstract: Cognitive impairment is a common comorbidity in temporal lobe epilepsy (TLE) and is often considered more detrimental to quality of life than seizures. While it has been previously shown that the encoding of memory during behavior is impaired in the pilocarpine model of TLE in rats, how this information is consolidated during the subsequent sleep period remains unknown. In this study, we first report marked deficits in spatial memory performance and severe cell loss in the CA1 layer of the hippocampus lower spatial coherence of firing in TLE rats. We then present the first evidence that the reactivation of behavior-driven patterns of activity of CA1 place cells in the hippocampus is intact in TLE rats. Using a template-matching method, we discovered that real-time (3-5 s) reactivation structure was intact in TLE rats. Furthermore, we estimated the entropy rate of short time scale (∼250 ms) bursting activity using block entropies and found that significant, extended temporal correlations exist in both TLE and control rats. Fitting a first-order Markov Chain model to these bursting time series, we found that long sequences derived from behavior were significantly enriched in the Markov model over corresponding models fit on randomized data confirming the presence of replay in shorter time scales. We propose that the persistent consolidation of poor spatial information in both real time and during bursting activity may contribute to memory impairments in TLE rats.
authors.affiliation: Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: A S
authors.initials: AS
authors.lastname: Titiz
authors.forename: J M
authors.initials: JM
authors.lastname: Mahoney
authors.forename: M E
authors.initials: ME
authors.lastname: Testorf
authors.forename: G L
authors.initials: GL
authors.lastname: Holmes
authors.forename: R C
authors.initials: RC
authors.lastname: Scott
mesh_terms: D000200:Action Potentials; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D015897:Comorbidity; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D018021:Lithium Chloride; D008390:Markov Chains; D018782:Maze Learning / Q000502:physiology; D008959:Models, Neurological; D010862:Pilocarpine; D017966:Pyramidal Cells / Q000473:pathology / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D012890:Sleep / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology*; D013997:Time Factors
chemical_list: D010862:Pilocarpine; D018021:Lithium Chloride
keywords: Markov chain; place cells; reactivation; replay; sleep