On the role of L-type Ca2+ and BK channels in a biophysical model of cartwheel interneurons
Cartwheel interneurons (CWCs) in the auditory system exhibit a range of activity patterns relevant to auditory function and pathologies. Although experiments have shown how these patterns can vary across individual neurons and can change under pharmacological manipulations, the field has lacked a computational framework in which to explore the contributions of particular currents to these observations and to generate new predictions about the effects of manipulations on CWCs. In this work, we address this deficiency by presenting a conductance-based CWC computational model. This model captures the diversity of CWC activity patterns observed experimentally and suggests parameter changes that may underlie differences across cells. Bifurcation analysis of this model provides an explanation of how distinct dynamic mechanisms contribute to these differences, while direct simulations suggest how cells with different baseline dynamics will respond to variations in certain experimentally-accessible potassium and calcium channel conductances. In addition to the full model that we introduce, we present a reduced model that preserves CWC dynamic regimes. We classify the reduced model variables in terms of distinct dynamic timescales and show that the key transitions in dynamic patterns can be explained based on equilibria of the averaged dynamics of the slowest model variables, in a regime where the faster model variables exhibit oscillations. Overall, this study predicts how changes in parameters will influence CWC behavior, suggests how bifurcations contribute to changes in CWC dynamics, and provides a theoretical foundation that supports our simulation findings.