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

Area of Science:

• Neuroscience
• Genetics
• Computational Biology

Background:

• Coordinated cortical activity is crucial for voluntary movement planning.
• Disruptions in cortical 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 impact on preparatory cortical dynamics is not well understood.

Purpose of the Study:

• To investigate the impact of SHANK3 gene mutations on cortex-wide activity during movement preparation.
• To elucidate the neural mechanisms underlying motor deficits associated with SHANK3 mutations in ASD models.

Main Methods:

• Utilized wide-field calcium imaging in Shank3b+/- mice to monitor cortex-wide neural activity.
• Combined imaging with motion tracking and computational motif analysis to correlate neural dynamics with spontaneous forepaw movements.
• Examined spatiotemporal patterns of cortical activity and network motifs during motor preparation.

Main Results:

• Observed reduced correlation between cortical activity and behavior preceding 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 in the mutant mice.

Conclusions:

• Disrupted spatiotemporal cortical dynamics in Shank3b+/- mice impair preparatory motor processes.
• These findings provide insights into the neural basis of ASD-related motor deficits.
• SHANK3 mutations impact cortical network function, contributing to motor planning impairments in ASD.