Jimmy Suh

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 NMDARs 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 R1 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 N1 ERP latency was delayed, sociability was reduced, and mating USVs were impaired in PV-selective NMDA Receptor 1 Knockout (NR1 KO) as compared with wild-type mice. There was a significant correlation between N1 latency and sociability but not between N1 latency and premating USV power or T-maze performance. The increases in N1 latency, impaired sociability, and reduced vocalizations in PV-selective NR1 KO mice mimic similar changes found in autism. Electrophysiological changes correlate to reduced sociability, indicating that the local circuit mechanisms controlling N1 latency may be utilized in social function. Therefore, we propose that behavioral and electrophysiological alterations in PV-selective NR1 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.

Reductions in the levels of the neuropeptide vasopressin (VP) and its receptors have been associated with schizophrenia. VP is also critical for appropriate social behaviors in humans as well as rodents. One of the prominent symptoms of schizophrenia is asociality and these symptoms may develop prodromally. A reduction in event-related potential (ERP) peak amplitudes is an endophenotype of schizophrenia. In this study, we use the Brattleboro (BRAT) rat to assess the role of VP deficiency in vocal communication during early development and on auditory ERPs during adulthood. BRAT rats had similar vocal communication to wild-type littermate controls during postnatal days 2 and 5 but the time between vocalizations was increased and the power of the vocalizations was reduced beginning at postnatal day 9. During adulthood, BRAT rats had deficits in auditory ERPs including reduced N40 amplitude and reduced low and high gamma intertrial coherence. These results suggest that the role of VP on vocal communication is an age-dependent process. Additionally, the deficits in ERPs indicate an impairment of auditory information processing related to the reduction in VP. Therefore, manipulation of the VP system could provide a novel mechanism for treatment for negative symptoms of schizophrenia.