Predicting single spikes and spike patterns with the Hindmarsh-Rose model

Most simple neuron models are only able to model traditional spiking behavior. As physiologists discover and classify different electrical phenotypes, computational neuroscientists become interested in using simple phenomenological models that can exhibit these different types of spiking patterns. The Hindmarsh-Rose model is a three-dimensional relaxation oscillator which can show both spiking and bursting patterns and has a chaotic regime. We test the predictive powers of the Hindmarsh-Rose model on two different test databases. We show that the Hindmarsh-Rose model can predict the spiking response of rat layer 5 neocortical pyramidal neurons on a stochastic input signal with a precision comparable to the best known spiking models. We also show that the Hindmarsh-Rose model can capture qualitatively the electrical footprints in a database of different types of neocortical interneurons. When the model parameters are fit from sub-threshold measurements only, the model still captures well the electrical phenotype, which suggests that the sub-threshold signals contain information about the firing patterns of the different neuron

Computational Modeling of Seizure Dynamics Using Coupled Neuronal Networks: Factors Shaping Epileptiform Activity

International audienceEpileptic seizure dynamics span multiple scales in space and time. Understanding seizure mechanisms requires identifying the relations between seizure components within and across these scales, together with the analysis of their dynamical repertoire. Mathematical models have been developed to reproduce seizure dynamics across scales ranging from the single neuron to the neural population. In this study, we develop a network model of spiking neurons and systematically investigate the conditions, under which the network displays the emergent dynamic behaviors known from the Epileptor, which is a well-investigated abstract model of epileptic neural activity. This approach allows us to study the biophysical parameters and variables leading to epileptiform discharges at cellular and network levels. Our network model is composed of two neuronal populations, characterized by fast excitatory bursting neurons and regular spiking inhibitory neurons, embedded in a common extracellular environment represented by a slow variable. By systematically analyzing the parameter landscape offered by the simulation framework, we reproduce typical sequences of neural activity observed during status epilepticus. We find that exogenous fluctuations from extracellular environment and electro-tonic couplings play a major role in the progression of the seizure, which supports previous studies and further validates our model. We also investigate the influence of chemical synaptic coupling in the generation of spontaneous seizure-like events. Our results argue towards a temporal shift of typical spike waves with fast discharges as synaptic strengths are varied. We demonstrate that spike waves, including interictal spikes, are generated primarily by inhibitory neurons, whereas fast discharges during the wave part are due to excitatory neurons. Simulated traces are compared with in vivo experimental data from rodents at different stages of the disorder. We draw the conclusion that slow variations of global excitability, due to exogenous fluctuations from extracellular environment, and gap junction communication push the system into paroxysmal regimes. We discuss potential mechanisms underlying such machinery and the relevance of our approach, supporting previous detailed modeling studies and reflecting on the limitations of our methodology

Predicting single spikes and spike patterns with the Hindmarsh–Rose model

Most simple neuron models are only able to model traditional spiking behavior. As physiologists discover and classify different electrical phenotypes, computational neuroscientists become interested in using simple phenomenological models that can exhibit these different types of spiking patterns. The Hindmarsh–Rose model is a three-dimensional relaxation oscillator which can show both spiking and bursting patterns and has a chaotic regime. We test the predictive powers of the Hindmarsh–Rose model on two different test databases. We show that the Hindmarsh–Rose model can predict the spiking response of rat layer 5 neocortical pyramidal neurons on a stochastic input signal with a precision comparable to the best known spiking models. We also show that the Hindmarsh–Rose model can capture qualitatively the electrical footprints in a database of different types of neocortical interneurons. When the model parameters are fit from sub-threshold measurements only, the model still captures well the electrical phenotype, which suggests that the sub-threshold signals contain information about the firing patterns of the different neurons

Conductance-Based Neuron Models and the Slow Dynamics of Excitability

In recent experiments, synaptically isolated neurons from rat cortical culture, were stimulated with periodic extracellular fixed-amplitude current pulses for extended durations of days. The neuron’s response depended on its own history, as well as on the history of the input, and was classified into several modes. Interestingly, in one of the modes the neuron behaved intermittently, exhibiting irregular firing patterns changing in a complex and variable manner over the entire range of experimental timescales, from seconds to days. With the aim of developing a minimal biophysical explanation for these results, we propose a general scheme, that, given a few assumptions (mainly, a timescale separation in kinetics) closely describes the response of deterministic conductance-based neuron models under pulse stimulation, using a discrete time piecewise linear mapping, which is amenable to detailed mathematical analysis. Using this method we reproduce the basic modes exhibited by the neuron experimentally, as well as the mean response in each mode. Specifically, we derive precise closed-form input-output expressions for the transient timescale and firing rates, which are expressed in terms of experimentally measurable variables, and conform with the experimental results. However, the mathematical analysis shows that the resulting firing patterns in these deterministic models are always regular and repeatable (i.e., no chaos), in contrast to the irregular and variable behavior displayed by the neuron in certain regimes. This fact, and the sensitive near-threshold dynamics of the model, indicate that intrinsic ion channel noise has a significant impact on the neuronal response, and may help reproduce the experimentally observed variability, as we also demonstrate numerically. In a companion paper, we extend our analysis to stochastic conductance-based models, and show how these can be used to reproduce the details of the observed irregular and variable neuronal response

Analysis of traveling wave propagation in one-dimensional integrate-and-fire neural networks

One-dimensional neural networks comprised of large numbers of Integrate-and-Fire neurons have been widely used to model electrical activity propagation in neural slices. Despite these efforts, the vast majority of these computational models have no analytical solutions. Consequently, my Ph.D. research focuses on a specific class of homogeneous Integrate-and-Fire neural network, for which analytical solutions of network dynamics can be derived. One crucial analytical finding is that the traveling wave acceleration quadratically depends on the instantaneous speed of the activity propagation, which means that two speed solutions exist in the activities of wave propagation: one is fast-stable and the other is slow-unstable. Furthermore, via this property, we analytically compute temporal-spatial spiking dynamics to help gain insights into the stability mechanisms of traveling wave propagation. Indeed, the analytical solutions are in perfect agreement with the numerical solutions. This analytical method also can be applied to determine the effects induced by a non-conductive gap of brain tissue and extended to more general synaptic connectivity functions, by converting the evolution equations for network dynamics into a low-dimensional system of ordinary differential equations. Building upon these results, we investigate how periodic inhomogeneities affect the dynamics of activity propagation. In particular, two types of periodic inhomogeneities are studied: alternating regions of additional fixed excitation and inhibition, and cosine form inhomogeneity. Of special interest are the conditions leading to propagation failure. With similar analytical procedures, explicit expressions for critical speeds of activity propagation are obtained under the influence of additional inhibition and excitation. However, an explicit formula for speed modulations is difficult to determine in the case of cosine form inhomogeneity. Instead of exact solutions from the system of equations, a series of speed approximations are constructed, rendering a higher accuracy with a higher order approximation of speed

Modellierung und Analyse des Thalamokortischen Systems

Physiological evidence localizes the thalamocortical system as the functional unit being responsible for the perception of sensory input. In this thesis the dynamical processes in the thalamus during sleep are reduced to their bare bones. For this purpose the dynamical behavior of conductance based neuron models, which describe biophysical details with high accuracy, is investigated and reduced models of this behavior are derived. The simplified models derived in this thesis allow an explanation of how sensory perception is strongly decreased during sleep within the framework of nonlinear dynamics. A minimal model for such a mechanism is derived, coarse graining out details but preserving most salient dynamical features. If several of these models are coupled in a network the experimental observed influence of cortical slow-wave oscillations on thalamic spindle oscillations during deep sleep can be reproduced. In particular the influence of cortical oscillations on the synchrony in a thalamic network is studied and the underlying control mechanism is uncovered, leading to a control method which might be applicable for several types of oscillations in the central nervous system.Physiologisch betrachtet ist das thalamokortische System für die Verarbeitung und Wahrnehmung von sensorischen Reizen zuständig. In dieser Arbeit werden die dynamischen Vorgänge im Thalamus während des Schlafes auf ihre grundlegenden Eigenschaften reduziert. Dazu wird das dynamische Verhalten von komplexen Neuronenmodellen untersucht, die biophysikalische Details mit hoher Genauigkeit wiedergeben und vereinfachte Modelle dieses Verhaltens eingeführt. Diese vereinfachten Modelle erlauben es, mit Hilfe der nichtlinearen Dynamik den Rückgang der sensorischen Wahrnehmung im Schlaf zu erklären. Dazu wird ein minimales Modell für den zugrunde liegenden Mechanismus abgeleitet, in dem Details vernachlässigt werden, ohne dass jedoch die wichtigsten dynamischen Eigenschaften verloren gehen. Koppelt man viele dieser Modelle in einem Netzwerk, so lässt sich der experimentell beobachtete Einfluss kortikaler Oszillationen auf thalamische Oszillationen reproduzieren. Ein besonderes Augenmerk liegt dabei auf der Synchronisation der thalamischen Oszillationen und dem zugrunde liegenden Mechanismus, welcher möglicherweise auch in anderen neuronalen Systemen anwendbar ist

Optimal Control and Synchronization of Dynamic Ensemble Systems

Ensemble control involves the manipulation of an uncountably infinite collection of structurally identical or similar dynamical systems, which are indexed by a parameter set, by applying a common control without using feedback. This subject is motivated by compelling problems in quantum control, sensorless robotic manipulation, and neural engineering, which involve ensembles of linear, bilinear, or nonlinear oscillating systems, for which analytical control laws are infeasible or absent. The focus of this dissertation is on novel analytical paradigms and constructive control design methods for practical ensemble control problems. The first result is a computational method %based on the singular value decomposition (SVD) for the synthesis of minimum-norm ensemble controls for time-varying linear systems. This method is extended to iterative techniques to accommodate bounds on the control amplitude, and to synthesize ensemble controls for bilinear systems. Example ensemble systems include harmonic oscillators, quantum transport, and quantum spin transfers on the Bloch system. To move towards the control of complex ensembles of nonlinear oscillators, which occur in neuroscience, circadian biology, electrochemistry, and many other fields, ideas from synchronization engineering are incorporated. The focus is placed on the phenomenon of entrainment, which refers to the dynamic synchronization of an oscillating system to a periodic input. Phase coordinate transformation, formal averaging, and the calculus of variations are used to derive minimum energy and minimum mean time controls that entrain ensembles of non-interacting oscillators to a harmonic or subharmonic target frequency. In addition, a novel technique for taking advantage of nonlinearity and heterogeneity to establish desired dynamical structures in collections of inhomogeneous rhythmic systems is derived

Neuron models of the generic bifurcation type:network analysis and data modeling

Minimal nonlinear dynamic neuron models of the generic bifurcation type may provide the middle way between the detailed models favored by experimentalists and the simplified threshold and rate model of computational neuroscientists. This thesis investigates to which extent generic bifurcation type models grasp the essential dynamical features that may turn out play a role in cooperative neural behavior. The thesis considers two neuron models, of increasing complexity, and one model of synaptic interactions. The FitzHugh-Nagumo model is a simple two-dimensional model capable only of spiking behavior, and the Hindmarsh-Rose model is a three-dimensional model capable of more complex dynamics such as bursting and chaos. The model for synaptic interactions is a memory-less nonlinear function, known as fast threshold modulation (FTM). By means of a combination of nonlinear system theory and bifurcation analysis the dynamical features of the two models are extracted. The most important feature of the FitzHugh-Nagumo model is its dynamic threshold: the spike threshold does not only depend on the absolute value, but also on the amplitude of changes in the membrane potential. Part of the very complex, intriguing bifurcation structure of the Hindmarsh-Rose model is revealed. By considering basic networks of FTM-coupled FitzHugh-Nagumo (spiking) or Hindmarsh-Rose (bursting) neurons, two main cooperative phenomena, synchronization and coincidence detections, are addressed. In both cases it is illustrated that pulse coupling in combination with the intrinsic dynamics of the models provides robustness. In large scale networks of FTM-coupled bursting neurons, the stability of complete synchrony is independent from the network topology and depends only on the number of inputs to each neuron. The analytical results are obtained under very restrictive and biologically implausible hypotheses, but simulations show that the theoretical predictions hold in more realistic cases as well. Finally, the realism of the models is put to a test by identification of their parameters from in vitro measurements. The identification problem is addressed by resorting to standard techniques combined with heuristics based on the results of the reported mathematical analysis and on a priori knowledge from neuroscience. The FitzHugh-Nagumo model is only able to model pyramidal neurons and even then performs worse than simple threshold models; it should be used only when the advantages of the more realistic threshold mechanism are prevalent. The Hindmarsh-Rose model can model much of the diversity of neocortical neurons; it can be used as a model in the study of heterogeneous networks and as a realistic model of a pyramidal neuron