Differential induction of the ZENK gene in the avian forebrain and song control circuit after metrazole-induced depolarization.

ZENK is an immediate early gene (IEG) that encodes a transcription factor protein, and its induction has been proposed as a necessary step in the cellular process underlying long-term memory formation. We have previously shown that ZENK is induced in adult songbird brain by the sound of birdsong, but, interestingly, induction did not occur in several areas known to respond to song stimuli. Conceivably, the ZENK gene may be repressed in these areas in adult birds. As a further test of this hypothesis, we administered metrazole, a strong GABAergic antagonist that leads to widespread excitation in the brain. Following metrazole, ZENK mRNA increases more than 10-fold throughout most of the telencephalon in both canaries and zebra finches, and primarily in neurons. In contrast, ZENK induction is much lower or absent in the archistriatum, the primary telencephalic sensory-recipient areas (including auditory field L), and the three telencephalic androgen receptor-containing song nuclei (high vocal center, lateral magnocellular nucleus of the anterior neostriatum, and the robust nucleus of the archistriatum). We did not observe any differences in ZENK induction patterns in juvenile versus adult zebra finches, or fall versus spring male canaries. Together with our previous studies of induction by song, these results suggest that in specific parts of the forebrain, including most of the song control system, IEG expression is subject to different constraints than in the rest of the forebrain. Understanding the molecular basis for this differential gene regulation may prove invaluable in understanding the organization of the song control circuit and the avian telencephalon.