Abstract. Mixed-mode oscillations (MMOs) are trajectories of a dynamical system in which there is an alternation between oscillations of distinct large and small amplitudes. MMOs have been observed and studied for over thirty years in chemical, physical, and biological systems. Few attempts have been made thus far to classify different patterns of MMOs, in contrast to the classification of the related phenomena of bursting oscillations. This paper gives a survey of different types of MMOs, concentrating its analysis on MMOs whose small-amplitude oscillations are produced by a local, multiple-time-scale "mechanism." Recent work gives substantially improved insight into the mathematical properties of these mechanisms. In this survey, we unify diverse observations about MMOs and establish a systematic framework for studying their properties. Numerical methods for computing different types of invariant manifolds and their intersections are an important aspect of the analysis described in this paper.

This paper is concerned with the geometry of slow manifolds of a dynamical system with two slow and one fast variable. Specifically, we study the dynamics near a folded node singularity, which is known to give rise to so-called canard solutions. Geometrically, canards are intersection curves of two-dimensional attracting and repelling slow manifolds, and they are a key element of slow-fast dynamics. For example, canard solutions are associated with mixed-mode oscillations, where they organize regions with different numbers of small oscillations. We perform a numerical study of the geometry of two-dimensional slow manifolds in the normal form of a folded node in R 3. Namely, we view the part of a slow manifold that is of interest as a one-parameter family of orbit segments up to a suitable cross-section. Hence, it is the solution of a two-point boundary value problem, which we solve by numerical continuation with the package AUTO. The computed family of orbit segments is used to obtain a mesh representation of the manifold as a surface. With this approach we show how the attracting and repelling slow manifolds change in dependence on the eigenvalue ratio µ of the reduced flow. At µ = 1 two primary canards bifurcate and secondary canards are created at odd integer values of µ. We compute 24 secondary canards to investigate how they spiral more and more around one of the primary canards. The first twelve secondary canards are continued in µ to obtain a numerical bifurcation diagram.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life.

We investigate the organization of mixed-mode oscillations in the self-coupled FitzHugh-Nagumo system. These types of oscillations can be explained as a combination of relaxation oscillations and small-amplitude oscillations controlled by canard solutions that are associated with a folded singularity on a critical manifold. The self-coupled FitzHugh-Nagumo system has a cubic critical manifold for a range of parameters, and an associated folded singularity of node-type. Hence, there exist corresponding attracting and repelling slow manifolds that intersect in canard solutions. We present a general technique for the computation of two-dimensional slow manifolds (smooth surfaces). It is based on a boundary value problem approach where the manifolds are computed as one-parameter families of orbit segments. Visualization of the computed surfaces gives unprecedented insight into the geometry of the system. In particular, our techniques allow us to find and visualize canard solutions as the intersection curves of the attracting and repelling slow manifolds.

This article concerns the phenomenon of Mixed-Mode Bursting Oscillations (MMBOs). These are solutions of fast-slow systems of ordinary differential equations that exhibit both small-amplitude oscillations (SAOs) and bursts consisting of one or multiple large-amplitude oscillations (LAOs). The name MMBO is given in analogy to Mixed-Mode Oscillations, which consist of alternating SAOs and LAOs, without the LAOs being organized into burst events. In this article, we show how MMBOs are created naturally in systems that have a spike-adding bifurcation or spike-adding mechanism, and in which the dynamics of one (or more) of the slow variables causes the system to pass slowly through that bifurcation. Canards are central to the dynamics of MMBOs, and their role in shaping the MMBOs is two-fold: saddle-type canards are involved in the spike-adding mechanism of the underlying burster and permit one to understand the number of LAOs in each burst event, and folded-node canards arise due to the slow passage effect and control the number of SAOs. The analysis is carried out for a prototypical fourth-order system of this type, which consists of the third-order Hindmarsh-Rose system, known to have the spike-adding mechanism, and in which one of the key bifurcation parameters also varies slowly. We also include a discussion of the MMBO phenomenon for the Morris-Lecar-Terman system. Finally, we discuss the role of the MMBOs to a biological modeling of secreting neurons.