title: Impaired hippocampal-dependent memory and reduced parvalbumin-positive interneurons in a ketamine mouse model of schizophrenia.
abstract: The hippocampus of patients with schizophrenia displays aberrant excess neuronal activity which affects cognitive function. Animal models of the illness have recapitulated the overactivity in the hippocampus, with a corresponding regionally localized reduction of inhibitory interneurons, consistent with that observed in patients. To better understand whether cognitive function is similarly affected in these models of hippocampal overactivity, we tested a ketamine mouse model of schizophrenia for cognitive performance in hippocampal- and medial prefrontal cortex (mPFC)-dependent tasks. We found that adult mice exposed to ketamine during adolescence were impaired on a trace fear conditioning protocol that relies on the integrity of the hippocampus. Conversely, the performance of the mice was normal on a delayed response task that is sensitive to mPFC damage. We confirmed that ketamine-exposed mice had reduced parvalbumin-positive interneurons in the hippocampus, specifically in the CA1, but not in the mPFC in keeping with the behavioral findings. These results strengthened the utility of the ketamine model for preclinical investigations of hippocampal overactivity in schizophrenia.
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: mtkoh@jhu.edu.
authors.forename: Ming Teng
authors.initials: MT
authors.lastname: Koh
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sherwood
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Dani R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects / Q000523:psychology; D006624:Hippocampus / Q000473:pathology*; D007395:Interneurons / Q000378:metabolism*; D007649:Ketamine / Q000633:toxicity*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010320:Parvalbumins / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D013997:Time Factors
chemical_list: D010320:Parvalbumins; D007649:Ketamine; D000661:Amphetamine
keywords: Delayed response task; Fear conditioning; Hippocampus; Medial prefrontal cortex; Overactivity
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