Co-induction of activity-dependent genes in songbirds

Song behavior in songbirds induces the expression of activity-dependent genes in brain areas involved in perceptual processing, production and learning of song. This genomic response is thought to represent a link between neuronal activation and long-term changes in song-processing circuits of the songbird brain. Here we demonstrate that Arc, an activity-regulated gene whose product has dendritic localization and is associated with synaptic plasticity, is rapidly induced by song in the brain of zebra finches. We show that, in the context of song auditory stimulation, Arc expression is induced in several telencephalic auditory areas, most prominently the caudomedial nidopallium and mesopallium, whereas in the context of singing, Arc is also induced in song control areas, namely nucleus HVC, used as a proper name, the robust nucleus of the arcopallium and the interface nucleus of the nidopallium. We also show that song-induced Arc expression co-localizes at the cellular level with those of the transcriptional regulators zenk and c-fos, and that the song induction of these three genes is dependent on activation of the mitogen-activated protein kinase signaling pathway. These findings provide evidence for an involvement of Arc in the brain's response to birdsong. They also demonstrate that genes representing distinct genomic and cellular regulatory programs, namely early effectors and transcription factors, are co-activated in the same neuronal cells by a naturally learned stimulus.