Towards a unified model of action potential generation

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 DESCRIPTION (provided by applicant): The axon initial segment has a unique composition of ion channels that enables action potential initiation. Studying the biophysical properties of this compartment is crucial for understanding neuronal excitability and associated neuronal disorders, including epilepsy. Recently, we found that Ca channels are clustered in the initial segment. Our lab showed that those channels play a critical role in neuronal excitability, and that these channels are subject to dopamine neuromodulation. Modern models of the initial segment includes realistic distributions of Na and K channels, but do not include Ca channels. Here, our goal is to utilize electrophysiological and imaging techniques, both in acute brain slice and heterologous systems, to understand the role of Ca channels in action potential initiation, and to determine how dopaminergic signaling alters the biophysical properties of axonal Ca channels. These data will be incorporated into new models of axon initial segment excitability using novel, GPU-based simulation environments.