Abstract #1364

A cross-species link between deficient synaptic pruning and functional hyper-connectivity in autism

Marco Pagani¹, Alice Bertero^1,2, Alessia De Felice¹, Andrea Locarno³, Ieva Miseviciute³, Stavros Trakoshis^4,5, Carola Canella^1,6, Elizabeth de Guzman¹, Kaushtub Supekar⁷, Vinod Menon⁷, Alberto Galbusera¹, Raffaella Tonini³, Michael V. Lombardo⁵, Massimo Pasqualetti², and Alessandro Gozzi¹

¹Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Rovereto, Italy, ²Biology Department, University of Pisa, Pisa, Italy, ³Neuromodulation of Cortical and Subcortical Circuits Laboratory, Istituto Italiano di Tecnologia, Genova, Italy, ⁴Department of Psychology, University of Cyprus, Nicosia, Cyprus, ⁵Laboratory for Autism and Neurodevelopmental Disorders, Istituto Italiano di Tecnologia, Rovereto, Italy, ⁶Center for Mind and Brain Sciences, University of Trento, Rovereto, Italy, ⁷Stanford University, Stanford, CA, United States

Altered brain functional connectivity is a hallmark finding in autism but the neural basis of this phenomenon remains unclear. We show that a mouse line reconstituting synaptic pruning deficits observed in postmortem autistic brains exhibits widespread functional hyper-connectivity, and that pharmacological normalization of synaptic aberrancies completely rescues behavioral and functional connectivity deficits. We also show that a similar connectivity fingerprint can be isolated in human rsfMRI scans of people with autism, and linked to overexpression of genes related to this dysfunctional pathway. Our results reveal a possible mechanistic link between deficient synaptic pruning and functional hyper-connectivity in autism.

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