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Abnormal Whisker-Dependent Behaviors and Altered Cortico-Hippocampal Connectivity in Shank3b-/- Mice
Luigi Balasco1, Marco Pagani2, Luca Pangrazzi1
1CIMeC - Center for Mind/Brain Sciences, University of Trento, 38068 Rovereto, TN, Italy.
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.
Insights
Mice with Shank3 gene mutations, similar to Autism Spectrum Disorders (ASDs), show reduced responses to touch. This sensory hypo-responsiveness is linked to decreased brain activity and connectivity between the somatosensory cortex and hippocampus.
Area of Science:
- Neuroscience
- Autism Spectrum Disorders Research
- Genetics
Background:
- Abnormal tactile responses, particularly hypo-responsiveness, are common in Autism Spectrum Disorders (ASDs) and correlate with symptom severity.
- Phelan-McDermid syndrome (PMS), linked to SHANK3 gene mutations, exhibits ASD-like symptoms and altered tactile processing.
- The precise neural mechanisms behind these tactile abnormalities in ASDs remain unclear.
Purpose of the Study:
- To investigate the neural basis of whisker-guided behaviors in Shank3b-/- mice, a model for PMS and ASD-like symptoms.
- To assess whisker-dependent sensory processing and associated neural activity in Shank3b-/- mice.
Main Methods:
- Behavioral testing using textured novel object recognition (tNORT) and whisker nuisance (WN) tests in Shank3b-/- mice and controls.
- Measurement of neuronal activation via c-fos mRNA induction in the primary somatosensory cortex (S1) and hippocampus following whisker stimulation.
- Resting-state functional magnetic resonance imaging (fMRI) to evaluate S1-hippocampal connectivity.
Main Results:
- Shank3b-/- mice demonstrated deficits in texture discrimination and exhibited hypo-responsiveness to whisker stimulation.
- Reduced neuronal activation was observed in the primary somatosensory cortex (S1) and hippocampus of Shank3b-/- mice.
- A significant decrease in resting-state functional connectivity between S1 and the hippocampus was found in Shank3b mutants.
Conclusions:
- Impaired whisker-guided behaviors in Shank3b-/- mice are associated with sensory hypo-responsiveness.
- Reduced S1-hippocampal connectivity may underlie the observed tactile deficits, suggesting a broader somatosensory dysfunction in ASD models.
