<p>Mutations of the FOXP2 gene impair speech and language development in humans and shRNA-mediated suppression of the avian orthologue 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. Using a combination of behavioral analysis, in vivo intracellular recordings in anaesthetized birds, pharmacology and extracellular recordings in singing birds, I addressed how FoxP2 knockdown in songbird striatum affects vocal control and signal propagation through circuits important for the control of learned vocalizations. In summary, I found that FoxP2 knockdown in the songbird striatum disrupts developmental and social modulation of song variability. Recordings in anaesthetized 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.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/8219 |
| Date | January 2013 |
| Creators | Murugan, Malavika |
| Contributors | Mooney, Richard |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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