Abnormal whisker-dependent behaviors and altered cortico-hippocampal connectivity in Shank3b−/− mice
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 s...
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Veröffentlicht in: | Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2022-07, Vol.32 (14), p.3042-3056 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1047-3211 1460-2199 |
DOI: | 10.1093/cercor/bhab399 |