Neurobiological basis of connectivity deficits in autism

  • Awarded: 2016
  • Award Type: Pilot
  • Award #: 400101

Neuroimaging studies have described altered structural and functional connectivity across brain regions of individuals with autism spectrum disorder (ASD). These findings have led to the hypothesis that altered brain connectivity may provide a key pathophysiological contribution in ASD. However the neurobiological determinants and significance of these findings remain unclear.

Alessandro Gozzi and his colleagues recently developed functional magnetic resonance imaging (fMRI) methods to map brain connectivity networks in the living mouse brain. Their results show that the mouse brain presents large-scale, synchronized neuronal networks analogous to those mapped with fMRI in people, including plausible mouse homologues of the human default-mode and salience networks1. Recently, the laboratory has observed analogous prefrontal hypo-connectivity in three well-characterized mouse models of ASD, namely CNTNAP2 null mice2, SHANK3 null mutants (unpublished data), and mice carrying a hemizygous deletion syntenic to 16p11.2 deletion syndrome (unpublished data).

Gozzi and his colleagues now plan to probe the role of additional genetic etiologies to understand whether the observed connectional signatures can be regarded as a generalizable phenomenon, or are mutation specific. To this aim, they will measure connectivity in two additional mouse models of ASDs that recapitulate core autism traits in mice, namely mice with triple genetic dosage of UBE3A (a model for dup15q syndrome) and TSC2 heterozygous mice (a model for tuberous sclerosis complex). By comparing the results from these studies with the previous data collected from assessments of CNTNAP2, SHANK3 and 16p11.2 deletion mouse models, these experiments will provide detailed insight into the determinants and significance of connectivity aberrancies associated with genetic mutations underlying ASDs.



1.Liska A. et al. Neuroimage 115, 281-291 (2015) PubMed
2.Liska A. et al. bioRxiv Epub ahead of print (2016) Abstract
Subscribe to our newsletter and receive SFARI funding announcements and news