We combine bifurcation analysis with the theory of canard-induced mixed mode oscillations to investigate the dynamics of a novel form of bursting. This bursting oscillation, which arises from a model of the electrical activity of a pituitary cell, is characterized by small impulses or spikes riding on top of an elevated voltage plateau. Oscillations with these characteristics have been called “pseudo-plateau bursting”. Unlike standard bursting, the subsystem of fast variables does not posses a stable branch of periodic spiking solutions, and in the case studied here the standard fast/slow analysis provides little information about the underlying dynamics. We demonstrate that the bursting is actually a canard-induced mixed mode oscillation, and use canard theory to characterize the dynamics of the oscillation. We also use bifurcation analysis of the full system of equations to extend the results of the singular analysis to the physiological regime. This demonstrates that the combination of these two analysis techniques can be a powerful tool for understanding the pseudo-plateau bursting oscillations that arise in electrically excitable pituitary cells and isolated pancreatic β-cells.

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The electrical activity of endocrine pituitary cells is mediated by a plethora of ionic currents and establishing the role of a single channel type is difficult. Experimental observations have shown however that fast-activating voltage- and calcium-dependent potassium (BK) current tends to promote bursting in pituitary cells. This burst promoting effect requires fast activation of the BK current, otherwise it is inhibitory to bursting. In this work, we analyze a pituitary cell model in order to answer the question of why the BK activation must be fast to promote bursting. We also examine how the interplay between the activation rate and conductance of the BK current shapes the bursting activity. We use the multiple timescale structure of the model to our advantage and employ geometric singular perturbation theory to demonstrate the origin of the bursting behaviour. In particular, we show that the bursting can arise from either canard dynamics or slow passage through a dynamic Hopf bifurcation. We then compare our theoretical predictions with experimental data using the dynamic clamp technique and find that the data is consistent with a burst mechanism due to a slow passage through a Hopf.

Pituitary cells of the anterior pituitary gland secrete hormones in response to patterns of electrical activity. Several types of pituitary cells produce short bursts of electrical activity which are more effective than single spikes in evoking hormone release. These bursts, called pseudo-plateau bursts, are unlike bursts studied mathematically in neurons (plateau bursting) and the standard fast-slow analysis used for plateau bursting is of limited use. Using an alternative fast-slow analysis, with one fast and two slow variables, we show that pseudo-plateau bursting is a canard-induced mixed mode oscillation. Using this technique, it is possible to determine the region of parameter space where bursting occurs as well as salient properties of the burst such as the number of spikes in the burst. The information gained from this one-fast/two-slow decomposition complements the information obtained from a two-fast/one-slow decomposition.

Mixed mode oscillations (MMOs) are complex oscillatory waveforms that naturally occur in physiologically relevant dynamical processes. MMOs were studied in a model of electrical bursting in a pituitary lactotroph [34] where geometric singular perturbation theory and bifurcation analysis were combined to demonstrate that the MMOs arise from canard dynamics. In this work, we extend the analysis done in [34] and consider bifurcations of canard solutions under variations of key parameters. To do this, a global return map induced by the flow of the equations is constructed and a qualitative analysis given. The canard solutions act as separatrices in the return maps, organising the dynamics along the Poincaré section. We examine the bifurcations of the return maps and demonstrate that the map formulation allows for an explanation of the different MMO patterns observed in the lactotroph model.

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Abstract. Pseudo-plateau bursting is a type of oscillatory waveform associated with mixed mode dynamics in slow/fast systems and commonly found in neural bursting models. In a recent model for the electrical activity and calcium signaling in a pituitary lactotroph, two types of pseudo-plateau bursts were discovered: one in which the calcium drives the bursts and another in which the calcium simply follows them. Multiple methods from dynamical systems theory have been used to understand the bursting. The classic 2-timescale approach treats the calcium concentration as a slowly varying parameter and considers a parametrized family of fast subsystems. A more novel and successful 2-timescale approach divides the system so that there is only one fast variable and shows that the bursting arises from canard dynamics. Both methods can be effective analytic tools, but there has been little justification for one approach over the other. In this work, we use the lactotroph model to demonstrate that the two analysis techniques are different unfoldings of a 3-timescale system. We show that elementary applications of geometric singular perturbation theory in the 2-timescale and 3-timescale methods provide us with substantial predictive power. We use that predictive power to explain the transient and long-term dynamics of the pituitary lactotroph model.