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Abnormal Whisker-Dependent Behaviors and Altered Cortico-Hippocampal Connectivity in Shank3b-/- Mice.

  • Balasco, Luigi1
  • Pagani, Marco2
  • Pangrazzi, Luca1
  • Chelini, Gabriele1
  • Ciancone Chama, Alessandra Georgette1
  • Shlosman, Evgenia1
  • Mattioni, Lorenzo3
  • Galbusera, Alberto2
  • Iurilli, Giuliano4
  • Provenzano, Giovanni3
  • Gozzi, Alessandro2
  • Bozzi, Yuri1, 5
  • 1 CIMeC - Center for Mind/Brain Sciences, University of Trento, 38068 Rovereto, TN, Italy. , (Italy)
  • 2 Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, 38068 Rovereto, TN, Italy. , (Italy)
  • 3 Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy. , (Italy)
  • 4 Systems Neurobiology Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, 38068 Rovereto, TN, Italy. , (Italy)
  • 5 CNR Neuroscience Institute, 56124 Pisa, Italy. , (Italy)
Published Article
Cerebral Cortex
Oxford University Press
Publication Date
Nov 18, 2021
DOI: 10.1093/cercor/bhab399
PMID: 34791077


Abnormal tactile response is an integral feature of Autism Spectrum Disorders (ASDs), and hypo-responsiveness to tactile stimuli is often associated with the severity of ASDs core symptoms. Patients with Phelan-McDermid syndrome (PMS), caused by mutations in the SHANK3 gene, show ASD-like symptoms associated with aberrant tactile responses. The neural underpinnings of these abnormalities are still poorly understood. Here we investigated, in Shank3b-/- adult mice, the neural substrates of whisker-guided behaviors, a key component of rodents' interaction with the surrounding environment. We assessed whisker-dependent behaviors in Shank3b-/- adult mice and age-matched controls, using the textured novel object recognition (tNORT) and whisker nuisance (WN) test. Shank3b-/- mice showed deficits in whisker-dependent texture discrimination in tNORT and behavioral hypo-responsiveness to repetitive whisker stimulation in WN. Sensory hypo-responsiveness was accompanied by a significantly reduced activation of the primary somatosensory cortex (S1) and hippocampus, as measured by c-fos mRNA induction, a proxy of neuronal activity following whisker stimulation. Moreover, resting-state fMRI showed a significantly reduced S1-hippocampal connectivity in Shank3b mutants, in the absence of altered connectivity between S1 and other somatosensory areas. Impaired crosstalk between hippocampus and S1 might underlie Shank3b-/- hypo-reactivity to whisker-dependent cues, highlighting a potentially generalizable somatosensory dysfunction in ASD. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

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