Robust and tunable bursting requires slow positive feedback

Abstract

We highlight that the robustness and tunability of a bursting model critically rely on currents that provide slow positive feedback to the membrane potential. Such currents have the ability to make the total conductance of the circuit negative in a timescale that is termed “slow” because it is intermediate between the fast timescale of the spike upstroke and the ultraslow timescale of even slower adaptation currents. We discuss how such currents can be assessed either in voltage-clamp experiments or in computational models. We show that, while frequent in the literature, mathematical and computational models of bursting that lack the slow negative conductance are fragile and rigid. Our results suggest that modeling the slow negative conductance of cellular models is important when studying the neuromodulation of rhythmic circuits at any broader scale. NEW & NOTEWORTHY Nervous system functions rely on the modulation of neuronal activity between different rhythmic patterns. The mechanisms of this modulation are still poorly understood. Using computational modeling, we show the critical role of currents that provide slow negative conductance, distinct from the fast negative conductance necessary for spike generation. The significance of the slow negative conductance for neuromodulation is often overlooked, leading to computational models that are rigid and fragile.