title: Impaired hippocampal ripple-associated replay in a mouse model of schizophrenia.
abstract: The cognitive symptoms of schizophrenia presumably result from impairments of information processing in neural circuits. We recorded neural activity in the hippocampus of freely behaving mice that had a forebrain-specific knockout of the synaptic plasticity-mediating phosphatase calcineurin and were previously shown to exhibit behavioral and cognitive abnormalities, recapitulating the symptoms of schizophrenia. Calcineurin knockout (KO) mice exhibited a 2.5-fold increase in the abundance of sharp-wave ripple (SWR) events during awake resting periods and single units in KO were overactive during SWR events. Pairwise measures of unit activity, however, revealed that the sequential reactivation of place cells during SWR events was completely abolished in KO. Since this relationship during postexperience awake rest periods has been implicated in learning, working memory, and subsequent memory consolidation, our findings provide a mechanism underlying impaired information processing that may contribute to the cognitive impairments in schizophrenia.
authors.affiliation: RIKEN-MIT Center for Neural Circuit Genetics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: junghyup@mit.edu.
authors.forename: Junghyup
authors.initials: J
authors.lastname: Suh
authors.forename: David J
authors.initials: DJ
authors.lastname: Foster
authors.forename: Heydar
authors.initials: H
authors.lastname: Davoudi
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wilson
authors.forename: Susumu
authors.initials: S
authors.lastname: Tonegawa
mesh_terms: D000818:Animals; D058256:Brain Waves / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000201:enzymology / Q000503:physiopathology*; D019703:Calcineurin / Q000172:deficiency / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D012146:Rest / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D014851:Wakefulness / Q000502:physiology
chemical_list: D019703:Calcineurin