title: Heightened cortical excitability in aged rodents with memory impairment.
abstract: Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices. Strong correlations between cFos intensity and task performance across the activated network showed a tight coupling between excitability and cognitive phenotype in aging. Elevated neural excitability extending beyond the hippocampus to interconnected posterior cortex (retrosplenial/parietal) was reduced by treatment with levetiracetam, a therapeutic with behavioral efficacy that has previously translated from rodent models of age-related impairment and Alzheimer's disease to humans with amnestic mild cognitive impairment.
authors.affiliation: Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, MD, USA. Electronic address: rahabs@jhu.edu.
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Haberman
authors.affiliation: Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Ming Teng
authors.initials: MT
authors.lastname: Koh
authors.affiliation: Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D003071:Cognition; D004195:Disease Models, Animal; D000077287:Levetiracetam; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020318:Rats, Long-Evans
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000077287:Levetiracetam; D010889:Piracetam
keywords: Aging; Hippocampal hyperactivity; Levetiracetam; Memory; Parietal cortex; Retrosplenial cortex