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

摘要: Author(s): Berg, Elizabeth L; Copping, Nycole A; Rivera, Josef K; Pride, Michael C; Careaga, Milo; Bauman, Melissa D; Berman, Robert F; Lein, Pamela J; Harony-Nicolas, Hala; Buxbaum, Joseph Ellegood, Jacob; Lerch, Jason P; Wohr, Markus; Silverman, Jill L | Abstract: Mutations in the SHANK3 gene have been discovered autism spectrum disorder (ASD), and intellectual disability, Phelan-McDermid Syndrome. This study leveraged a new rat model of Shank3 deficiency to assess complex behavioral phenomena, unique rats, which display richer social behavior repertoire than mice. Uniquely detectable emissions ultrasonic vocalizations (USV) rats serve as situation-dependent affective signals accomplish important communicative functions. We report, for first time, call response acoustic playback assay bidirectional communication juvenile rats. Interestingly, we found that Shank3-deficient null males did not demonstrate enhanced approach typically exhibited following pro-social USV. Concomitantly, emission USV was genotype-dependent emitted calls were divergent meaning. is report these socially relevant responses using genetic ASD. A comprehensive empirical analysis vigorous play during reciprocal interactions further revealed fewer bouts reduced durations time spent playing by multiple key parameters, including anogenital sniffing allogrooming. male pups isolation-induced wildtype controls. Postnatal whole brain anatomical phenotyping applied visualize substrates underlie developmental phenotypes. The data presented here lend support role communication, core symptom domain By increasing number vivo functional outcome measures, improved likelihood identifying moving forward with medical interventions. Autism Res 2018, 11: 587-601. © 2018 International Society Research, Wiley Periodicals, Inc.Lay summaryClinically outcomes are required utility therapeutics. introduce findings model, impact mutations Shank3, an risk gene. deficient expression typical bi-directional test interaction lower on parameters. Outcome measures reported herein extend earlier results mice capture calls, analogous measuring receptive expressive communication.