title: An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning.
abstract: Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor integration and motor-skill learning, in particular corticostriatal circuits. Independent studies in multiple species suggest that the striatum is a key site of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to investigate the effects of the KE-family mutation on the function of striatal circuits during motor-skill learning. We uncovered abnormally high ongoing striatal activity in mice carrying an identical mutation to that of the KE family. Furthermore, there were dramatic alterations in striatal plasticity during the acquisition of a motor skill, with most neurons in mutants showing negative modulation of firing rate, starkly contrasting with the predominantly positive modulation seen in control animals. We also observed striking changes in the temporal coordination of striatal firing during motor-skill learning in mutants. Our results indicate that FOXP2 is critical for the function of striatal circuits in vivo, which are important not only for speech but also for other striatal-dependent skills.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: French
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.forename: T G
authors.initials: TG
authors.lastname: Campbell
authors.forename: E
authors.initials: E
authors.lastname: Gerfen
authors.forename: M
authors.initials: M
authors.lastname: Groszer
authors.forename: S E
authors.initials: SE
authors.lastname: Fisher
authors.forename: R M
authors.initials: RM
authors.lastname: Costa
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009048:Motor Skills / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D045442:Rotarod Performance Test / Q000379:methods
chemical_list: D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D012097:Repressor Proteins