Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder

Elizabeth L. Berg, Nycole A. Copping, Josef K. Rivera, Michael C. Pride, Milo Careaga, Melissa D. Bauman, Robert F. Berman, Pamela J. Lein, Hala Harony-Nicolas, Joseph D. Buxbaum, Jacob Ellegood, Jason P. Lerch, Markus Wöhr, Jill L. Silverman

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Mutations in the SHANK3 gene have been discovered in autism spectrum disorder (ASD), and the intellectual disability, Phelan-McDermid Syndrome. This study leveraged a new rat model of Shank3 deficiency to assess complex behavioral phenomena, unique to rats, which display a richer social behavior repertoire than mice. Uniquely detectable emissions of ultrasonic vocalizations (USV) in rats serve as situation-dependent affective signals and accomplish important communicative functions. We report, for the first time, a call and response acoustic playback assay of bidirectional social communication in juvenile Shank3 rats. Interestingly, we found that Shank3-deficient null males did not demonstrate the enhanced social approach behavior typically exhibited following playback of pro-social USV. Concomitantly, we discovered that emission of USV in response to playback was not genotype-dependent and emitted response calls were divergent in meaning. This is the first report of these socially relevant responses using a genetic model of ASD. A comprehensive and empirical analysis of vigorous play during juvenile reciprocal social interactions further revealed fewer bouts and reduced durations of time spent playing by multiple key parameters, including reduced anogenital sniffing and allogrooming. We further discovered that male null Shank3-deficient pups emitted fewer isolation-induced USV than Shank3 wildtype controls. Postnatal whole brain anatomical phenotyping was applied to visualize anatomical substrates that underlie developmental phenotypes. The data presented here lend support for the important role of Shank3 in social communication, the core symptom domain of ASD. By increasing the number of in vivo functional outcome measures, we improved the likelihood for identifying and moving forward with medical interventions.

Original languageEnglish (US)
JournalAutism Research
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Animal model
  • Autism
  • Behavior
  • Neurodevelopment
  • Phelan McDermid Syndrome
  • Shank
  • Social
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)

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    Berg, E. L., Copping, N. A., Rivera, J. K., Pride, M. C., Careaga, M., Bauman, M. D., Berman, R. F., Lein, P. J., Harony-Nicolas, H., Buxbaum, J. D., Ellegood, J., Lerch, J. P., Wöhr, M., & Silverman, J. L. (Accepted/In press). Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder. Autism Research. https://doi.org/10.1002/aur.1925