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.

Abnormal Whisker-Dependent Behaviors and Altered Cortico-Hippocampal Connectivity in Shank3b−/− Mice / Balasco, Luigi; Pagani, Marco; Pangrazzi, Luca; Chelini, Gabriele; Georgette Ciancone Chama, Alessandra; Shlosman, Evgenia; Mattioni, Lorenzo; Galbusera, Alberto; Iurilli, Giuliano; Provenzano, Giovanni; Gozzi, Alessandro; Bozzi, Yuri. - In: CEREBRAL CORTEX. - ISSN 1460-2199. - 2021:(2021), pp. 1-14. [10.1093/cercor/bhab399]

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

Luigi Balasco;Marco Pagani;Luca Pangrazzi;Gabriele Chelini;Giovanni Provenzano;Yuri Bozzi
2021-01-01

Abstract

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.
2021
Balasco, Luigi; Pagani, Marco; Pangrazzi, Luca; Chelini, Gabriele; Georgette Ciancone Chama, Alessandra; Shlosman, Evgenia; Mattioni, Lorenzo; Galbusera, Alberto; Iurilli, Giuliano; Provenzano, Giovanni; Gozzi, Alessandro; Bozzi, Yuri
Abnormal Whisker-Dependent Behaviors and Altered Cortico-Hippocampal Connectivity in Shank3b−/− Mice / Balasco, Luigi; Pagani, Marco; Pangrazzi, Luca; Chelini, Gabriele; Georgette Ciancone Chama, Alessandra; Shlosman, Evgenia; Mattioni, Lorenzo; Galbusera, Alberto; Iurilli, Giuliano; Provenzano, Giovanni; Gozzi, Alessandro; Bozzi, Yuri. - In: CEREBRAL CORTEX. - ISSN 1460-2199. - 2021:(2021), pp. 1-14. [10.1093/cercor/bhab399]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/323485
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