Nonlinear synchrony dynamics of neuronal bursters

We study the appearance of a novel phenomenon for coupled identical bursters: synchronized bursts where there are changes of spike synchrony within each burst. The examples we study are for normal form elliptic bursters where there is a periodic slow passage through a Bautin (codimension two degenerate Andronov-Hopf) bifurcation. This burster has a subcritical Andronov-Hopf bifurcation at the onset of repetitive spiking while the end of burst occurs via a fold limit cycle bifurcation. We study synchronization behavior of two Bautin-type elliptic bursters for a linear direct coupling scheme as well as demonstrating its presence in an approximation of gap-junction and synaptic coupling. We also find similar behaviour in system consisted of three and four Bautin-type elliptic bursters. We note that higher order terms in the normal form that do not affect the behavior of a single burster can be responsible for changes in synchrony pattern; more precisely, we find within-burst synchrony changes associated with a turning point in the spontaneous spiking frequency (frequency transition). We also find multiple synchrony changes in similar system by incorporating multiple frequency transitions. To explain the phenomenon we considered a burst-synchronized constrained model and a bifurcation analysis of the this reduced model shows the existence of the observed within-burst synchrony states. Within-burst synchrony change is also found in the system of mutually delaycoupled two Bautin-type elliptic bursters with a constant delay. The similar phenomenon is shown to exist in the mutually-coupled conductance-based Morris-Lecar neuronal system with an additional slow variable generating elliptic bursting. We also find within-burst synchrony change in linearly coupled FitzHugh-Rinzel 2 3 elliptic bursting system where the synchrony change occurs via a period doubling bifurcation. A bifurcation analysis of a burst-synchronized constrained system identifies the periodic doubling bifurcation in this case. We show emergence of spontaneous burst synchrony cluster in the system of three Hindmarsh-Rose square-wave bursters with nonlinear coupling. The system is found to change between the available cluster states depending on the stimulus. Lyapunov exponents of the burst synchrony states are computed from the corresponding variational system to probe the stability of the states. Numerical simulation also shows existence of burst synchrony cluster in the larger network of such system.Exeter Research Scholarship

Modeling the Influence of Ion Channels on Neuron Dynamics in Drosophila

abstract: Voltage gated ion channels play a major role in determining a neuron's firing behavior, resulting in the specific processing of synaptic input patterns. Drosophila and other invertebrates provide valuable model systems for investigating ion channel kinetics and their impact on firing properties. Despite the increasing importance of Drosophila as a model system, few computational models of its ion channel kinetics have been developed. In this study, experimentally observed biophysical properties of voltage gated ion channels from the fruitfly Drosophila melanogaster are used to develop a minimal, conductance based neuron model. We investigate the impact of the densities of these channels on the excitability of the model neuron. Changing the channel densities reproduces different in situ observed firing patterns and induces a switch from integrator to resonator properties. Further, we analyze the preference to input frequency and how it depends on the channel densities and the resulting bifurcation type the system undergoes. An extension to a three dimensional model demonstrates that the inactivation kinetics of the sodium channels play an important role, allowing for firing patterns with a delayed first spike and subsequent high frequency firing as often observed in invertebrates, without altering the kinetics of the delayed rectifier current.View the article as published at http://journal.frontiersin.org/article/10.3389/fncom.2015.00139/ful

Mechanisms of Firing Patterns in Fast-Spiking Cortical Interneurons

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na+, delayed-rectifier K+, and slowly inactivating d-type K+ conductances. The model is analyzed using nonlinear dynamical system theory. For small Na+ window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, gd, and it is delayed for larger gd. As gd further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na+ window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their gd and in the strength of their Na+ window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction

Robust spike timing in an excitable cell with delayed feedback

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this recordData and materials availability: Data and computer code related to the mathematical model and dynamic clamp experiments can be downloaded from the GitHub repository https://github.com/SlowinskiPiotr/MorrisLecarDDEThe initiation and regeneration of pulsatile activity is a ubiquitous feature observed in excitable systems with delayed feedback. Here, we demonstrate this phenomenon in a real biological cell. We establish a critical role of the delay resulting from the finite propagation speed of electrical impulses on the emergence of persistent multiple-spike patterns. We predict the co-existence of a number of such patterns in a mathematical model and use a biological cell subject to dynamic clamp to confirm our predictions in a living mammalian system. Given the general nature of our mathematical model and experimental system, we believe that our results capture key hallmarks of physiological excitability that are fundamental to information processing.Medical Research Council (MRC)Wellcome TrustEngineering and Physical Sciences Research Council (EPSRC)Technical University of Munich – Institute for Advanced StudyRoyal Societ

Investigating the role of fast-spiking interneurons in neocortical dynamics

PhD ThesisFast-spiking interneurons are the largest interneuronal population in neocortex. It is well documented that this population is crucial in many functions of the neocortex by subserving all aspects of neural computation, like gain control, and by enabling dynamic phenomena, like the generation of high frequency oscillations. Fast-spiking interneurons, which represent mainly the parvalbumin-expressing, soma-targeting basket cells, are also implicated in pathological dynamics, like the propagation of seizures or the impaired coordination of activity in schizophrenia. In the present thesis, I investigate the role of fast-spiking interneurons in such dynamic phenomena by using computational and experimental techniques. First, I introduce a neural mass model of the neocortical microcircuit featuring divisive inhibition, a gain control mechanism, which is thought to be delivered mainly by the soma-targeting interneurons. Its dynamics were analysed at the onset of chaos and during the phenomena of entrainment and long-range synchronization. It is demonstrated that the mechanism of divisive inhibition reduces the sensitivity of the network to parameter changes and enhances the stability and exibility of oscillations. Next, in vitro electrophysiology was used to investigate the propagation of activity in the network of electrically coupled fast-spiking interneurons. Experimental evidence suggests that these interneurons and their gap junctions are involved in the propagation of seizures. Using multi-electrode array recordings and optogenetics, I investigated the possibility of such propagating activity under the conditions of raised extracellular K+ concentration which applies during seizures. Propagated activity was recorded and the involvement of gap junctions was con rmed by pharmacological manipulations. Finally, the interaction between two oscillations was investigated. Two oscillations with di erent frequencies were induced in cortical slices by directly activating the pyramidal cells using optogenetics. Their interaction suggested the possibility of a coincidence detection mechanism at the circuit level. Pharmacological manipulations were used to explore the role of the inhibitory interneurons during this phenomenon. The results, however, showed that the observed phenomenon was not a result of synaptic activity. Nevertheless, the experiments provided some insights about the excitability of the tissue through scattered light while using optogenetics. This investigation provides new insights into the role of fast-spiking interneurons in the neocortex. In particular, it is suggested that the gain control mechanism is important for the physiological oscillatory dynamics of the network and that the gap junctions between these interneurons can potentially contribute to the inhibitory restraint during a seizure.Wellcome Trust

Ion Channel Density Regulates Switches between Regular and Fast Spiking in Soma but Not in Axons

The threshold firing frequency of a neuron is a characterizing feature of its dynamical behaviour, in turn determining its role in the oscillatory activity of the brain. Two main types of dynamics have been identified in brain neurons. Type 1 dynamics (regular spiking) shows a continuous relationship between frequency and stimulation current (f-Istim) and, thus, an arbitrarily low frequency at threshold current; Type 2 (fast spiking) shows a discontinuous f-Istim relationship and a minimum threshold frequency. In a previous study of a hippocampal neuron model, we demonstrated that its dynamics could be of both Type 1 and Type 2, depending on ion channel density. In the present study we analyse the effect of varying channel density on threshold firing frequency on two well-studied axon membranes, namely the frog myelinated axon and the squid giant axon. Moreover, we analyse the hippocampal neuron model in more detail. The models are all based on voltage-clamp studies, thus comprising experimentally measurable parameters. The choice of analysing effects of channel density modifications is due to their physiological and pharmacological relevance. We show, using bifurcation analysis, that both axon models display exclusively Type 2 dynamics, independently of ion channel density. Nevertheless, both models have a region in the channel-density plane characterized by an N-shaped steady-state current-voltage relationship (a prerequisite for Type 1 dynamics and associated with this type of dynamics in the hippocampal model). In summary, our results suggest that the hippocampal soma and the two axon membranes represent two distinct kinds of membranes; membranes with a channel-density dependent switching between Type 1 and 2 dynamics, and membranes with a channel-density independent dynamics. The difference between the two membrane types suggests functional differences, compatible with a more flexible role of the soma membrane than that of the axon membrane

Neural Cartography: Computer Assisted Poincare Return Mappings for Biological Oscillations

This dissertation creates practical methods for Poincaré return mappings of individual and networked neuron models. Elliptic bursting models are found in numerous biological systems, including the external Globus Pallidus (GPe) section of the brain; the focus for studies of epileptic seizures and Parkinson\u27s disease. However, the bifurcation structure for changes in dynamics remains incomplete. This dissertation develops computer-assisted Poincaré ́maps for mathematical and biologically relevant elliptic bursting neuron models and central pattern generators (CPGs). The first method, used for individual neurons, offers the advantage of an entire family of computationally smooth and complete mappings, which can explain all of the systems dynamical transitions. A complete bifurcation analysis was performed detailing the mechanisms for the transitions from tonic spiking to quiescence in elliptic bursters. A previously unknown, unstable torus bifurcation was found to give rise to small amplitude oscillations. The focus of the dissertation shifts from individual neuron models to small networks of neuron models, particularly 3-cell CPGs. A CPG is a small network which is able to produce specific phasic relationships between the cells. The output rhythms represent a number of biologically observable actions, i.e. walking or running gates. A 2-dimensional map is derived from the CPGs phase-lags. The cells are endogenously bursting neuron models mutually coupled with reciprocal inhibitory connections using the fast threshold synaptic paradigm. The mappings generate clear explanations for rhythmic outcomes, as well as basins of attraction for specific rhythms and possible mechanisms for switching between rhythms