Dynamical systems techniques in the analysis of neural systems

As we strive to understand the mechanisms underlying neural computation, mathematical models are increasingly being used as a counterpart to biological experimentation. Alongside building such models, there is a need for mathematical techniques to be developed to examine the often complex behaviour that can arise from even the simplest models. There are now a plethora of mathematical models to describe activity at the single neuron level, ranging from one-dimensional, phenomenological ones, to complex biophysical models with large numbers of state variables. Network models present even more of a challenge, as rich patterns of behaviour can arise due to the coupling alone. We first analyse a planar integrate-and-fire model in a piecewise-linear regime. We advocate using piecewise-linear models as caricatures of nonlinear models, owing to the fact that explicit solutions can be found in the former. Through the use of explicit solutions that are available to us, we categorise the model in terms of its bifurcation structure, noting that the non-smooth dynamics involving the reset mechanism give rise to mathematically interesting behaviour. We highlight the pitfalls in using techniques for smooth dynamical systems in the study of non-smooth models, and show how these can be overcome using non-smooth analysis. Following this, we shift our focus onto the use of phase reduction techniques in the analysis of neural oscillators. We begin by presenting concrete examples showcasing where these techniques fail to capture dynamics of the full system for both deterministic and stochastic forcing. To overcome these failures, we derive new coordinate systems which include some notion of distance from the underlying limit cycle. With these coordinates, we are able to capture the effect of phase space structures away from the limit cycle, and we go on to show how they can be used to explain complex behaviour in typical oscillatory neuron models

Dynamical systems techniques in the analysis of neural systems

As we strive to understand the mechanisms underlying neural computation, mathematical models are increasingly being used as a counterpart to biological experimentation. Alongside building such models, there is a need for mathematical techniques to be developed to examine the often complex behaviour that can arise from even the simplest models. There are now a plethora of mathematical models to describe activity at the single neuron level, ranging from one-dimensional, phenomenological ones, to complex biophysical models with large numbers of state variables. Network models present even more of a challenge, as rich patterns of behaviour can arise due to the coupling alone. We first analyse a planar integrate-and-fire model in a piecewise-linear regime. We advocate using piecewise-linear models as caricatures of nonlinear models, owing to the fact that explicit solutions can be found in the former. Through the use of explicit solutions that are available to us, we categorise the model in terms of its bifurcation structure, noting that the non-smooth dynamics involving the reset mechanism give rise to mathematically interesting behaviour. We highlight the pitfalls in using techniques for smooth dynamical systems in the study of non-smooth models, and show how these can be overcome using non-smooth analysis. Following this, we shift our focus onto the use of phase reduction techniques in the analysis of neural oscillators. We begin by presenting concrete examples showcasing where these techniques fail to capture dynamics of the full system for both deterministic and stochastic forcing. To overcome these failures, we derive new coordinate systems which include some notion of distance from the underlying limit cycle. With these coordinates, we are able to capture the effect of phase space structures away from the limit cycle, and we go on to show how they can be used to explain complex behaviour in typical oscillatory neuron models

An analysis of waves underlying grid cell firing in the medial enthorinal cortex

Layer II stellate cells in the medial enthorinal cortex (MEC) express hyperpolarisation-activated cyclic-nucleotide-gated (HCN) channels that allow for rebound spiking via an I_h current in response to hyperpolarising synaptic input. A computational modelling study by Hasselmo [2013 Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex. Phil. Trans. R. Soc. B 369: 20120523] showed that an inhibitory network of such cells can support periodic travelling waves with a period that is controlled by the dynamics of the I_h current. Hasselmo has suggested that these waves can underlie the generation of grid cells, and that the known difference in I_h resonance frequency along the dorsal to ventral axis can explain the observed size and spacing between grid cell firing fields. Here we develop a biophysical spiking model within a framework that allows for analytical tractability. We combine the simplicity of integrate-and-fire neurons with a piecewise linear caricature of the gating dynamics for HCN channels to develop a spiking neural field model of MEC. Using techniques primarily drawn from the field of nonsmooth dynamical systems we show how to construct periodic travelling waves, and in particular the dispersion curve that determines how wave speed varies as a function of period. This exhibits a wide range of long wavelength solutions, reinforcing the idea that rebound spiking is a candidate mechanism for generating grid cell firing patterns. Importantly we develop a wave stability analysis to show how the maximum allowed period is controlled by the dynamical properties of the I_h current. Our theoretical work is validated by numerical simulations of the spiking model in both one and two dimensions

Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

During embryogenesis, morphogens form a concentration gradient in responsive tissue, which is then translated into a spatial cellular pattern. The mechanisms by which morphogens spread through a tissue to establish such a morphogenetic field remain elusive. Here, we investigate by mutually complementary simulations and in vivo experiments how Wnt morphogen transport by cytonemes differs from typically assumed diffusion-based transport for patterning of highly dynamic tissue such as the neural plate in zebrafish. Stochasticity strongly influences fate acquisition at the single cell level and results in fluctuating boundaries between pattern regions. Stable patterning can be achieved by sorting through concentration dependent cell migration and apoptosis, independent of the morphogen transport mechanism. We show that Wnt transport by cytonemes achieves distinct Wnt thresholds for the brain primordia earlier compared with diffusion-based transport. We conclude that a cytoneme-mediated morphogen transport together with directed cell sorting is a potentially favored mechanism to establish morphogen gradients in rapidly expanding developmental systems

Limitations of perturbative techniques in the analysis of rhythms and oscillations

Perturbation theory is an important tool in the analysis of oscillators and their response to external stimuli. It is predicated on the assumption that the perturbations in question are “sufficiently weak”, an assumption that is not always valid when perturbative methods are applied. In this paper, we identify a number of concrete dynamical scenarios in which a standard perturbative technique, based on the infinitesimal phase response curve (PRC), is shown to give different predictions than the full model. Shear-induced chaos, i.e., chaotic behavior that results from the amplification of small perturbations by underlying shear, is missed entirely by the PRC. We show also that the presence of “sticky” phase–space structures tend to cause perturbative techniques to overestimate the frequencies and regularity of the oscillations. The phenomena we describe can all be observed in a simple 2D neuron model, which we choose for illustration as the PRC is widely used in mathematical neuroscience

Just another day in Chancery Lane: disorder and the law in London's legal quarter in the fifteenth century

The legal quarter of late medieval London – the district outside the city’s western gates which included eleven Inns of Court and of Chancery and the royal courts at Westminster and in Chancery Lane – was a liminal area. Rather than being a peaceful and law-abiding district, as at least one fifteenth-century apologist would have it, it was the setting for periodic outbreaks of violence fomented to a high degree by the tribalism of the communities of the various law schools. Litigation in the royal courts added provincial rivalries and disputes and their protagonists to this already heady mix, making the space between Temple Bar and Westminster Hall one notable for its explosive potential for outbreaks of violence. Using a case study of an incident in the early 1450s that is unusually well-evidenced in the court records, and other sources, including the well-known correspondence of the East Anglian Paston family, and that drew over time drew in litigants, witnesses, lawyers and eventually a magnate and his affinity, the article explores the tensions inherent in London’s legal district and their interplay with disputes and law-breaking in the regions

Macroscopic coherent structures in a stochastic neural network: from interface dynamics to coarse-grained bifurcation analysis

We study coarse pattern formation in a cellular automaton modelling a spatially-extended stochastic neural network. The model, originally proposed by Gong and Robinson (Phys Rev E 85(5):055,101(R), 2012), is known to support stationary and travelling bumps of localised activity. We pose the model on a ring and study the existence and stability of these patterns in various limits using a combination of analytical and numerical techniques. In a purely deterministic version of the model, posed on a continuum, we construct bumps and travelling waves analytically using standard interface methods from neural field theory. In a stochastic version with Heaviside firing rate, we construct approximate analytical probability mass functions associated with bumps and travelling waves. In the full stochastic model posed on a discrete lattice, where a coarse analytic description is unavailable, we compute patterns and their linear stability using equation-free methods. The lifting procedure used in the coarse time-stepper is informed by the analysis in the deterministic and stochastic limits. In all settings, we identify the synaptic profile as a mesoscopic variable, and the width of the corresponding activity set as a macroscopic variable. Stationary and travelling bumps have similar meso- and macroscopic profiles, but different microscopic structure, hence we propose lifting operators which use microscopic motifs to disambiguate them. We provide numerical evidence that waves are supported by a combination of high synaptic gain and long refractory times, while meandering bumps are elicited by short refractory times

Phase-amplitude descriptions of neural oscillator models

Phase oscillators are a common starting point for the reduced description of many single neuron models that exhibit a strongly attracting limit cycle. The framework for analysing such models in response to weak perturbations is now particularly well advanced, and has allowed for the development of a theory of weakly connected neural networks. However, the strong-attraction assumption may well not be the natural one for many neural oscillator models. For example, the popular conductance based Morris-Lecar model is known to respond to periodic pulsatile stimulation in a chaotic fashion that cannot be adequately described with a phase reduction. In this paper, we generalise the phase description that allows one to track the evolution of distance from the cycle as well as phase on cycle. We use a classical technique from the theory of ordinary differential equations that makes use of a moving coordinate system to analyse periodic orbits. The subsequent phase-amplitude description is shown to be very well suited to understanding the response of the oscillator to external stimuli (which are not necessarily weak). We consider a number of examples of neural oscillator models, ranging from planar through to high dimensional models, to illustrate the effectiveness of this approach in providing an improvement over the standard phase-reduction technique. As an explicit application of this phase-amplitude framework, we consider in some detail the response of a generic planar model where the strong-attraction assumption does not hold, and examine the response of the system to periodic pulsatile forcing. In addition, we explore how the presence of dynamical shear can lead to a chaotic response