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Knockout of NMDA Receptors in Parvalbumin Interneurons Recreates Autism‐Like Phenotypes
Author(s) -
Saunders John A.,
TatardLeitman Valerie M.,
Suh Jimmy,
Billingslea Eddie N.,
Roberts Timothy P.,
Siegel Steven J.
Publication year - 2013
Publication title -
autism research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 66
eISSN - 1939-3806
pISSN - 1939-3792
DOI - 10.1002/aur.1264
Subject(s) - autism , parvalbumin , neuroscience , electrophysiology , psychology , endophenotype , nmda receptor , latency (audio) , knockout mouse , autism spectrum disorder , neurodevelopmental disorder , cognition , receptor , biology , developmental psychology , genetics , electrical engineering , engineering
Autism is a disabling neurodevelopmental disorder characterized by social deficits, language impairment, and repetitive behaviors with few effective treatments. New evidence suggests that autism has reliable electrophysiological endophenotypes and that these measures may be caused by n‐methyl‐d‐aspartic acid receptor ( NMDAR ) disruption on parvalbumin ( PV )‐containing interneurons. These findings could be used to create new translational biomarkers. Recent developments have allowed for cell‐type selective knockout of NMDAR s in order to examine the perturbations caused by disrupting specific circuits. This study examines several electrophysiological and behavioral measures disrupted in autism using a PV ‐selective reduction in NMDA R 1 subunit. Mouse electroencephalograph ( EEG ) was recorded in response to auditory stimuli. Event‐related potential ( ERP ) component amplitude and latency analysis, social testing, and premating ultrasonic vocalizations ( USVs ) recordings were performed. Correlations were examined between the ERP latency and behavioral measures. The N 1 ERP latency was delayed, sociability was reduced, and mating USVs were impaired in PV ‐selective NMDA Receptor 1 Knockout ( NR 1 KO ) as compared with wild‐type mice. There was a significant correlation between N 1 latency and sociability but not between N 1 latency and premating USV power or T ‐maze performance. The increases in N 1 latency, impaired sociability, and reduced vocalizations in PV ‐selective NR 1 KO mice mimic similar changes found in autism. Electrophysiological changes correlate to reduced sociability, indicating that the local circuit mechanisms controlling N 1 latency may be utilized in social function. Therefore, we propose that behavioral and electrophysiological alterations in PV ‐selective NR 1 KO mice may serve as a useful model for therapeutic development in autism. Autism Res 2013, 6: 69–77. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.