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Abstract #1364

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

Marco Pagani1, Alice Bertero1,2, Alessia De Felice1, Andrea Locarno3, Ieva Miseviciute3, Stavros Trakoshis4,5, Carola Canella1,6, 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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