The goal for this revised two-year K25 Mentored Quantitative Research Career Development Award is for the PI to gain enough knowledge and research experience in neurobiology to make a transition from research in theoretical and computational physics to research in theoretical I neurobiology, especially as related to auditory-guided vocal learning of songbirds. Songbird research is important for the long-term goals of NIDCD because songbirds provide one of the few experimental paradigms to understand at the cellular and circuit levels how humans learn to speak and how speech pathologies may arise and be treated. Experiments have shown that the songbird telencephalic nucleus HVC is critical for song learning and song production. An intriguing property of HVC projection neurons is that they produce temporally sparse bursts of action potentials during singing and during song playback, and these bursts are thought to be important for auditory and motor encoding of the song. Under the guidance of mentor Professor Richard Mooney and over an 18-month period, the PI will learn experimental techniques and carry out three projects in the Mooney lab to clarify the mechanism and significance of the sparse bursts: single-electrode intracellular recordings in HVC slices to characterize the intrinsic dynamical properties of pharmacologically isolated HVC neurons; dual intracellular recordings of neurons that have been verified to be synaptically connected, to study how the sparse bursts of HVC-to-RA projection neurons influence the tonic firing of HVC interneurons; and dual-intracellular recordings combined with antidromic stimulation of HVC-to-RA projection neurons, to quantify the degree of convergence of projection neurons onto interneurons. The PI will use the experimental data obtained from these projects, together with a deeper understanding of theoretical neurobiology obtained during the K25, to develop and to improve mathematical models of how sparse preciselyaligned bursts arise in HVC, and especially to test the hypothesis that the bursts during singing are produced by an intrinsic causal mechanism such as a synfire chain. ? ? ?
