An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Mutations in the human FOXP2 gene are linked to speech and language impairments, notably in the KE family.
• The FOXP2 protein is conserved across vertebrates and plays a role in sensorimotor integration and motor learning, particularly within corticostriatal circuits.
• The striatum is identified as a critical site for FOXP2 function.

Purpose of the Study:

• To investigate the in vivo effects of the KE-family FOXP2 mutation on striatal circuit function during motor-skill learning in mice.

Main Methods:

• In vivo electrophysiological recordings were performed in awake, behaving mice with a KE-family FOXP2 mutation.
• Striatal activity and plasticity were analyzed during the acquisition of a motor skill.

Main Results:

• Mice with the KE-family mutation exhibited abnormally high ongoing activity in the striatum.
• Significant alterations in striatal plasticity were observed, with most mutant neurons showing negative firing rate modulation, unlike controls.
• Striking changes in the temporal coordination of striatal firing occurred during motor-skill learning in mutants.

Conclusions:

• FOXP2 is essential for the proper in vivo function of striatal circuits.
• These findings highlight FOXP2's critical role in motor-skill learning and sensorimotor integration, extending beyond its known impact on speech development.