Mechanisms of neuron excitability for vocalizations in songbirds

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Understanding how the brain controls fine motor skills such as playing the piano or producing vocalizations such as song requires knowing how electrical properties of brain cells are regulated. Songbirds, like the zebra finch, are excellent species for understanding how the brain controls fine motor skills involved in song production because the juvenile songbird learns to sing its species songs by imitating an adult of its species. The brain circuits involved in this imitative learning have been studied for many decades and are now well described. The project is aimed at understanding the electrical properties within these well-studied brain regions by focusing on the cells in these areas and how ions move in and out of channels in these cells to produce electrical properties. The goal of these studies is to measure precise electrical activity of these cells and to modify genes in these cells that may influence electrical properties thereby possibly affecting motor patterns during song production. These studies will expose undergraduate and high school students to cutting edge molecular and cellular neuroscience. Students will be recruited with a major emphasis on underrepresented minorities, including Latin-American trainees, through participation in a Summer Equity and Neuroscience Programs, presentations to Native American communities, and participation in minority-focused meetings. The results of our work will be available through publications, presentations at scientific conferences, science fairs and Brain Awareness events. We propose to study how intrinsic excitable properties of neurons are modulated within the brain circuitry that subserves a complex learned behavior. We will use zebra finches, a songbird species with a well characterized vocal circuitry, and focus on nucleus RA (robustus arcopallialis), a motor cortical area analogous to upper cortical vocal motor neurons in mammals. We have recently found that high-threshold voltage gated potassium channels (Kv3.1) are differentially expressed in RA and undergo marked developmental “switches” in expression, in concert with marked age differences in the excitable properties of RA neurons. We hypothesize that these molecular and cellular changes play key roles in shaping RA’s excitability properties and establishing features of adult RA (e.g. high firing rates and fidelity) that are important for the emerging bioacoustic features of song during the critical period for vocal acquisition. We will test these hypotheses using whole-cell patch clamp recordings in brain slices, in situ hybridization, and song bioacoustics analysis, as well as viral-based manipulations and dynamic clamp modeling to mechanistically test the role of specific key ion channel subunits in modulating the remarkably narrow action potentials of RA projection neurons.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.