Response modulation in the zebra finch neostriatum: relationship to nuclear gene regulation.

The sound of birdsong activates robust gene expression in the caudomedial neostriatum (NCM) of songbirds. To assess the function of this genomic response, we analyzed the temporal and quantitative relationships between electrophysiological activity and gene induction. Single units in zebra finch NCM showed large increases in firing in response to birdsong, whereas simple auditory tones tended to inhibit firing. Most cells showed little selectivity for individual songs based on total number of spikes produced. When a novel song stimulus was repeated, the cells rapidly modulated their firing rates so that the first response to a stimulus was markedly higher than consecutive responses. Even after many repetitions of a particular song, cells continued to fire in response to that stimulus, unlike the complete "habituation" observed previously for genomic activity. The initial modulation of the response to a particular song disappeared, however, once that song was repeated for 200 trials ( approximately 34 min). These results indicate a dissociation between gross physiological activity and "immediate early" gene expression: genomic activity occurs only during a subset of electrophysiological responses. We propose a model in which nuclear responses in NCM are modulated by pathways distinct from the primary auditory inputs to NCM. This would account for the changing selectivity of the genomic response and implies an active role for the cell nucleus as an integrating agent in the physiological operation of neural circuits.