Disrupted cortex-wide dynamics impair motor planning in Shank3-mutant mice

Area of Science:

• Neuroscience
• Computational Neuroscience
• Genetics

Background:

• Coordinated cortical activity is crucial for voluntary movement planning.
• Disruptions in this activity are linked to neurodevelopmental disorders, including autism spectrum disorder (ASD).
• SHANK3 gene mutations are a significant risk factor for ASD, affecting synaptic and network function, but their precise impact on preparatory cortical dynamics is not fully understood.

Purpose of the Study:

• To investigate the effects of Shank3 gene mutations on cortex-wide activity during motor planning.
• To elucidate the neural mechanisms underlying motor deficits associated with SHANK3 mutations in ASD.

Main Methods:

• Utilized wide-field calcium imaging in Shank3b+/- mice during spontaneous forepaw movements.
• Integrated motion tracking and computational motif analysis to examine cortical activity patterns.
• Assessed cortex-wide neural dynamics and their correlation with behavioral output.

Main Results:

• Observed reduced correlation between cortical activity and behavior before movement onset in Shank3b+/- mice.
• Found decreased expression of specific cortical motifs involving associative and motor areas.
• Identified global functional hyperconnectivity and impaired motor planning capabilities.

Conclusions:

• Shank3b gene mutation disrupts spatiotemporal cortical dynamics crucial for motor planning.
• Altered preparatory cortical processes in Shank3b mutant mice contribute to motor deficits observed in ASD.
• Provides insights into the neural basis of ASD-related motor impairments.