Impaired Hippocampal Ripple-Associated Replay in a Mouse Model of Schizophrenia
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Tonegawa_Impaired hippocampal.pdf
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Author(s)
Suh, Junghyup
Foster, David J.
Davoudi, Heydar
Wilson, Matthew A.
Tonegawa, Susumu
Foster, David J.
Wilson, Matthew A.
Date Issued
October 2013
Journal
Neuron
Publisher
Elsevier/Cell Press
Citation
Suh, Junghyup, David J. Foster, Heydar Davoudi, Matthew A. Wilson, Susumu Tonegawa. "Impaired Hippocampal Ripple-Associated Replay in a Mouse Model of Schizophrenia." Neuron 80, (2013) pp. 484–493.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
RIKEN-MIT Center for Neural Circuit Genetics
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2013.09.014
