The constitutive differential transcriptome of a brain circuit for vocal learning.

BACKGROUND: The ability to imitate the vocalizations of other organisms, a trait known as vocal learning, is shared by only a few organisms, including humans, where it subserves the acquisition of speech and language, and 3 groups of birds. In songbirds, vocal learning requires the coordinated activity of a set of specialized brain nuclei referred to as the song control system. Recent efforts have revealed some of the genes that are expressed in these vocal nuclei, however a thorough characterization of the transcriptional specializations of this system is still missing. We conducted a rigorous and comprehensive analysis of microarrays, and conducted a separate analysis of 380 genes by in situ hybridizations in order to identify molecular specializations of the major nuclei of the song system of zebra finches (Taeniopygia guttata), a songbird species. RESULTS: Our efforts identified more than 3300 genes that are differentially regulated in one or more vocal nuclei of adult male birds compared to the adjacent brain regions. Bioinformatics analyses provided insights into the possible involvement of these genes in molecular pathways such as cellular morphogenesis, intrinsic cellular excitability, neurotransmission and neuromodulation, axonal guidance and cela-to-cell interactions, and cell survival, which are known to strongly influence the functional properties of the song system. Moreover, an in-depth analysis of specific gene families with known involvement in regulating the development and physiological properties of neuronal circuits provides further insights into possible modulators of the song system. CONCLUSION: Our study represents one of the most comprehensive molecular characterizations of a brain circuit that evolved to facilitate a learned behavior in a vertebrate. The data provide novel insights into possible molecular determinants of the functional properties of the song control circuitry. It also provides lists of compelling targets for pharmacological and genetic manipulations to elucidate the molecular regulation of song behavior and vocal learning.