The role of FoxP2 for the development and function of neural circuits mediating vocal production learning

Project Leader: Constance Scharff e-mail


Mutations in the FOXP2 gene, coding for a forkhead transcription factor, cause a language and speech deficit, Developmental Verbal Dyspraxia. Using zebra finches as an animal model we have previously shown that deficits in vocal learning occur after experimental reduction of FoxP2 in Area X, a striatal nucleus involved in song imitation. In the reporting period we addressed the molecular and cellular mechanisms underlying this finding. We found that different Area X medium spiny neuron populations express FoxP1, 2 and 4 in distinct sets and that the different FoxP proteins can homo- and heterodimerize in vitro and in vivo. This is consistent with differential regulation of specific target sets in striatal microcircuits. In addition, we investigated downstream targets using a variety of in vitro and in vivo techniques. To test the effect of the different FoxPs on synaptic transmission in the striatum we established electrophysiological recording techniques in primary neurons, brain slices and with chronically implanted electrodes. Our data support the emerging notion that FoxP2 and associated molecular signaling networks affect cortico-striatal neural circuit function underlying vocal communication. Future work in this project aims at substantiating the relevance of the regulatory effects of FoxP1, 2 and 4 on target genes and of altered FoxP function on synaptic structure and function.