title: Diminished FoxP2 levels affect dopaminergic modulation of corticostriatal signaling important to song variability.
abstract: Mutations of the FOXP2 gene impair speech and language development in humans and shRNA-mediated suppression of the avian ortholog FoxP2 disrupts song learning in juvenile zebra finches. How diminished FoxP2 levels affect vocal control and alter the function of neural circuits important to learned vocalizations remains unclear. Here we show that FoxP2 knockdown in the songbird striatum disrupts developmental and social modulation of song variability. Recordings in anesthetized birds show that FoxP2 knockdown interferes with D1R-dependent modulation of activity propagation in a corticostriatal pathway important to song variability, an effect that may be partly attributable to reduced D1R and DARPP-32 protein levels. Furthermore, recordings in singing birds reveal that FoxP2 knockdown prevents social modulation of singing-related activity in this pathway. These findings show that reduced FoxP2 levels interfere with the dopaminergic modulation of vocal variability, which may impede song and speech development by disrupting reinforcement learning mechanisms.
authors.affiliation: Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Malavika
authors.initials: M
authors.lastname: Murugan
authors.affiliation: Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harward
authors.affiliation: Department of Animal Behavior, Freie Universität Berlin, Berlin 14195, Germany.
authors.forename: Constance
authors.initials: C
authors.lastname: Scharff
authors.affiliation: Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: mooney@neuro.duke.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Mooney
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D046369:Finches / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D055785:Gene Knockdown Techniques; D007858:Learning / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000378:metabolism / Q000502:physiology; D012919:Social Behavior; D014828:Vocalization, Animal / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D051858:Forkhead Transcription Factors; C506553:FoxP2 protein, zebrafish; D017447:Receptors, Dopamine D1; D029961:Zebrafish Proteins