Abnormal Whisker-Dependent Behaviors and Altered Cortico-Hippocampal Connectivity in Shank3b-/- Mice
Autor: | Alberto Galbusera, Giovanni Provenzano, Luca Pangrazzi, Yuri Bozzi, Luigi Balasco, Marco Pagani, Lorenzo Mattioni, Alessandra Georgette Ciancone Chama, Giuliano Iurilli, Gabriele Chelini, Alessandro Gozzi, Evgenia Shlosman |
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Rok vydání: | 2021 |
Předmět: |
hippocampus
Cognitive Neuroscience autism Hippocampus Stimulation Sensory system Chromosome Disorders Nerve Tissue Proteins autism connectivity hippocampus mouse somatosensory Hippocampal formation Biology Somatosensory system somatosensory SHANK3 Gene 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine medicine Premovement neuronal activity Animals mouse 030304 developmental biology Mice Knockout 0303 health sciences Microfilament Proteins Somatosensory Cortex medicine.disease Disease Models Animal connectivity Vibrissae Autism Neuroscience 030217 neurology & neurosurgery |
Zdroj: | Cerebral cortex (New York, N.Y. : 1991). 32(14) |
ISSN: | 1460-2199 |
Popis: | 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. |
Databáze: | OpenAIRE |
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