The Knockout of Synapsin II in Mice Impairs Social Behavior and Functional Connectivity Generating an ASD-like Phenotype

Caterina Michetti, Angela Caruso, Marco Pagani, Mara Sabbioni, Lucian Medrihan, Gergely David, Alberto Galbusera, Monica Morini, Alessandro Gozzi, Fabio Benfenati, Maria Luisa Scattoni

Research output: Contribution to journalArticlepeer-review

Abstract

Autism spectrum disorders (ASD) and epilepsy are neurodevelopmental conditions that appear with high rate of co-occurrence, suggesting the possibility of a common genetic basis. Mutations in Synapsin (SYN) genes, particularly SYN1 and SYN2, have been recently associated with ASD and epilepsy in humans. Accordingly, mice lacking Syn1 or Syn2, but not Syn3, experience epileptic seizures and display autistic-like traits that precede the onset of seizures. Here, we analyzed social behavior and ultrasonic vocalizations emitted in 2 social contexts by SynI, SynII, or SynIII mutants and show that SynII mutants display the most severe ASD-like phenotype. We also show that the behavioral SynII phenotype correlates with a significant decrease in auditory and hippocampal functional connectivity as measured with resting state functional magnetic resonance imaging (rsfMRI). Taken together, our results reveal a permissive contribution of Syn2 to the expression of normal socio-communicative behavior, and suggest that Syn2-mediated synaptic dysfunction can lead to ASD-like behavior through dysregulation of cortical connectivity.

Original languageEnglish
Pages (from-to)5014-5023
Number of pages10
JournalCerebral Cortex
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • autism
  • functional connectivity
  • social behavior
  • synapsin
  • ultrasonic vocalizations

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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