Impaired Hippocampal Ripple-Associated Replay in a Mouse Model of Schizophrenia

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. •Hippocampal SWRs are more abundant in calcineurin KO during awake rest•CA1 cells in KO display normal place-dependent response during active exploration•KO CA1 place cells are more active during SWR and participate in more SWRs•Replay of CA1 place cells during SWRs is abolished in KO Suh et al. demonstrate that sequential replay of hippocampal place cells during rest is abolished in a mouse model of schizophrenia, although place-dependent firing of those cells is normal, providing insight into information-processing impairments associated with the disorder.