Classification of bursting patterns: A tale of two ducks

Abstract

Bursting is one of the fundamental rhythms that excitable cells can generate either in response to incoming stimuli or intrinsically. It has been a topic of intense research in computational biology for several decades. The classification of bursting oscillations in excitable systems has been the subject of active research since the early 1980s and is still ongoing. As a by-product, it establishes analytical and numerical foundations for studying complex temporal behaviors in multiple timescale models of cellular activity. In this review, we first present the seminal works of Rinzel and Izhikevich in classifying bursting patterns of excitable systems. We recall a complementary mathematical classification approach by Bertram and colleagues, and then by Golubitsky and colleagues, which, together with the Rinzel-Izhikevich proposals, provide the state-of-the-art foundations to these classifications. Beyond classical approaches, we review a recent bursting example that falls outside the previous classification systems. Generalizing this example leads us to propose an extended classification, which requires the analysis of both fast and slow subsystems of an underlying slow-fast model and allows the dissection of a larger class of bursters. Namely, we provide a general framework for bursting systems with both subthreshold and superthreshold oscillations. A new class of bursters with at least 2 slow variables is then added, which we denote folded-node bursters, to convey the idea that the bursts are initiated or annihilated via a folded-node singularity. Key to this mechanism are so-called canard or duck orbits, organizing the underpinning excitability structure. We describe the 2 main families of folded-node bursters, depending upon the phase (active/spiking or silent/nonspiking) of the bursting cycle during which folded-node dynamics occurs. We classify both families and give examples of minimal systems displaying these novel bursting patterns. Finally, we provide a biophysical example by reinterpreting a generic conductance-based episodic burster as a folded-node burster, showing that the associated framework can explain its subthreshold oscillations over a larger parameter region than the fast subsystem approach. Author summary Bursting is ubiquitous in cellular excitable rhythms and comes in a plethora of patterns, both experimentally recorded and reproduced through models. As these different patterns may reflect different coding or information properties, it is therefore crucial to develop modeling frameworks that can both capture them and understand their characteristics. In this review, we propose a comprehensive account of the main bursting classification systems that have been developed over the past 40 years, together with recent developments allowing us to extend these classifications. Based upon bifurcation theory and heavily reliant on timescale separation, these schemes take full advantage of the fast subsystem analysis, obtained when slow variables are frozen and considered as bifurcation parameters. We complement this classical view by showing that nontrivial slow subsystem may also encode key informations important to classify bursting rhythms, due to the presence of so-called folded-node singularities. We provide minimal idealized models as well as one generic conductance-based example displaying bursting oscillations that require our extended classification in order to be fully characterized. We also highlight examples of biological data that could be suitably revisited with the lenses of this extended classifications and could lead to new models of complex cellular activity.