Birdsong is an excellent model for understanding the neural basis of complex vocal behavior, like human speech. Songbirds naturally learn and produce their song, and like human speech, the learning process depends on hearing. Our long-term goal is to understand the neural mechanisms of song production. As a beginning, this proposal considers the role played by the telencephalic nucleus HVc in zebra finches, which produce one song with high stereotypy throughout life. HVc is likely to participate in driving song production: it is required for singing, its neurons display premotor and patterned activity during song production, and it is poised anatomically to influence the output of the syrinx, the avian vocal organ. Furthermore, studies of HVc in vivo have implicated it as a pattern generator for song. The experiments described here propose to develop a slice preparation of HVc that can be induced to produce activity in vitro that mimics the rhythmic activity observed during song production in vivo. Recent indirect evidence shows that patterned activity can be elicited in brain slice preparations of HVc; the goal here is to directly observe the spiking activity, and to induce it reliably. Specifically, extracellular recordings will be used to monitor the spiking patterns of HVc cells in vitro in response to brief high frequency stimuli, application of neuromodulators, or both. If patterned activity results, we will analyze it for stereotypy and similarity to the song of the bird from which the brain slice was made. The proposal is highly exploratory because it aims to discover the conditions under which rhythmic, singing-related activity can be induced in HVc in vitro. This approach will at least clarify the extent to which HVc is capable of generating rhythmic activity in isolation. If these experiments yield reliable rhythmic activity related to song, then this will be a strong candidate for a preparation of """"""""fictive singing."""""""" Such a preparation would provide one of the few vertebrate examples of pattern generation in vitro, claim the first instance of in vitro pattern generation for vocal behavior within the telencephalon, and it would form a basis for future mechanistic investigations of rhythmic activity in HVc, song production, and more generally the motor control of sequenced and patterned motor outputs. This knowledge would be applicable to understanding the mechanisms governing speech production in humans, and enhance the understanding of speech, how it is learned, and its pathologies.
