Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

Abstract

Significance The human form of forkhead box P2 ( FOXP2 ) is the leading genetic candidate for human speech and language proficiency. We demonstrate that the introduction of the amino acid changes that occurred during human evolution into murine Foxp2 ( Foxp2 hum ) profoundly affects learning and striatal neuroplasticity. Foxp2 hum/hum mice learn stimulus–response associations more rapidly than WT mice when declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could interfere with one another. Dopamine levels, gene expression patterns, and synaptic physiology are oppositely affected in the striatal districts underpinning these learning forms, paralleling the behavioral change. We hypothesize that the human FOXP2 evolution led to differential tuning of corticostriatal systems involved in declarative and procedural learning and thus contributed to adapting the human brain for speech and language acquisition.