Synaptic reorganization of synchronized neuronal networks with synaptic weight and structural plasticity.

Abnormally strong neural synchronization may impair brain function, as observed in several brain disorders. We computationally study how neuronal dynamics, synaptic weights, and network structure co-emerge, in particular, during (de)synchronization processes and how they are affected by external perturbation. To investigate the impact of different types of plasticity mechanisms, we combine a network of excitatory integrate-and-fire neurons with different synaptic weight and/or structural plasticity mechanisms: (i) only spike-timing-dependent plasticity (STDP), (ii) only homeostatic structural plasticity (hSP), i.e., without weight-dependent pruning and without STDP, (iii) a combination of STDP and hSP, i.e., without weight-dependent pruning, and (iv) a combination of STDP and structural plasticity (SP) that includes hSP and weight-dependent pruning. To accommodate the diverse time scales of neuronal firing, STDP, and SP, we introduce a simple stochastic SP model, enabling detailed numerical analyses. With tools from network theory, we reveal that structural reorganization may remarkably enhance the network's level of synchrony. When weaker contacts are preferentially eliminated by weight-dependent pruning, synchrony is achieved with significantly sparser connections than in randomly structured networks in the STDP-only model. In particular, the strengthening of contacts from neurons with higher natural firing rates to those with lower rates and the weakening of contacts in the opposite direction, followed by selective removal of weak contacts, allows for strong synchrony with fewer connections. This activity-led network reorganization results in the emergence of degree-frequency, degree-degree correlations, and a mixture of degree assortativity. We compare the stimulation-induced desynchronization of synchronized states in the STDP-only model (i) with the desynchronization of models (iii) and (iv). The latter require stimuli of significantly higher intensity to achieve long-term desynchronization. These findings may inform future pre-clinical and clinical studies with invasive or non-invasive stimulus modalities aiming at inducing long-lasting relief of symptoms, e.g., in Parkinson's disease.

Dynamics of phase oscillator networks with synaptic weight and structural plasticity.

We study the dynamics of Kuramoto oscillator networks with two distinct adaptation processes, one varying the coupling strengths and the other altering the network structure. Such systems model certain networks of oscillatory neurons where the neuronal dynamics, synaptic weights, and network structure interact with and shape each other. We model synaptic weight adaptation with spike-timing-dependent plasticity (STDP) that runs on a longer time scale than neuronal spiking. Structural changes that include addition and elimination of contacts occur at yet a longer time scale than the weight adaptations. First, we study the steady-state dynamics of Kuramoto networks that are bistable and can settle in synchronized or desynchronized states. To compare the impact of adding structural plasticity, we contrast the network with only STDP to one with a combination of STDP and structural plasticity. We show that the inclusion of structural plasticity optimizes the synchronized state of a network by allowing for synchronization with fewer links than a network with STDP alone. With non-identical units in the network, the addition of structural plasticity leads to the emergence of correlations between the oscillators' natural frequencies and node degrees. In the desynchronized regime, the structural plasticity decreases the number of contacts, leading to a sparse network. In this way, adding structural plasticity strengthens both synchronized and desynchronized states of a network. Second, we use desynchronizing coordinated reset stimulation and synchronizing periodic stimulation to induce desynchronized and synchronized states, respectively. Our findings indicate that a network with a combination of STDP and structural plasticity may require stronger and longer stimulation to switch between the states than a network with STDP only.

Measuring chaos in the Lorenz and Rössler models: Fidelity tests for reservoir computing.

This study focuses on the qualitative and quantitative characterization of chaotic systems with the use of a symbolic description. We consider two famous systems, Lorenz and Rössler models with their iconic attractors, and demonstrate that with adequately chosen symbolic partition, three measures of complexity, such as the Shannon source entropy, the Lempel-Ziv complexity, and the Markov transition matrix, work remarkably well for characterizing the degree of chaoticity and precise detecting stability windows in the parameter space. The second message of this study is to showcase the utility of symbolic dynamics with the introduction of a fidelity test for reservoir computing for simulating the properties of the chaos in both models' replicas. The results of these measures are validated by the comparison approach based on one-dimensional return maps and the complexity measures.

Demixing of two species via reciprocally concentration-dependent diffusivity.

We propose a model for demixing of two species by assuming a density-dependent effective diffusion coefficient of the particles. Both sorts of microswimmers diffuse as active overdamped Brownian particles with a noise intensity that is determined by the surrounding density of the respective other species within a sensing radius r_{s}. A higher concentration of the first (second) sort will enlarge the diffusion and, in consequence, the intensity of the noise experienced by the second (first) sort. Numerical and analytical investigations of steady states of the macroscopic equations prove the demixing of particles due to this reciprocally concentration-dependent diffusivity. An ambiguity of the numerical integration scheme for the purely local model (r_{s}→0) is resolved by considering nonvanishing sensing radii in a nonlocal model with r_{s}>0.

Information processing in tree networks of excitable elements.

We study the collective response of small random tree networks of diffusively coupled excitable elements to stimuli applied to leaf nodes. Such networks model the morphology of certain sensory neurons that possess branched myelinated dendrites with excitable nodes of Ranvier at every branch point and at leaf nodes. Leaf nodes receive random inputs along with a stimulus and initiate action potentials that propagate through the tree. We quantify the collective response registered at the central node using mutual information. We show that in the strong-coupling limit, the statistics of the number of nodes and leaves determines the mutual information. At the same time, the collective response is insensitive to particular node connectivity and distribution of stimulus over leaf nodes. However, for intermediate coupling, the mutual information may strongly depend on the stimulus distribution among leaf nodes. We identify a mechanism behind the competition of leaf nodes that leads to nonmonotonous dependence of mutual information on coupling strength. We show that a localized stimulus given to a tree branch can be occluded by the background firing of unstimulated branches, thus suppressing mutual information. Nonetheless, the mutual information can be enhanced by a proper stimulus localization and tuning of coupling strength.

Vocal wow in an adapted reflex resonance model.

Vocal wow and tremor are slow modulations of the voice presumed to result from integration of auditory and somatosensory feedback, respectively. This distinction has important implications for diagnosis and treatment of neurological disorders that may differentially impact these systems, but the underlying mechanisms remain poorly understood. An important contribution on this matter is the reflex resonance model [Titze et al. (2002). J. Acoust. Soc. Am. 111(5), 2272-2282], which demonstrates that a 4-7 Hz vibrato (or tremor) can indeed be elicited by adjusting feedback parameters in a simple model of laryngeal muscle activation, mediated by time-delayed somatosensory feedback. This paper expands on this model by incorporating an auditory feedback loop and shows that wow emerges as feedback parameters exceed critical values described by a Hopf bifurcation. The wow period increases with delay and is almost invariant with respect to gain for delays above 200 ms. Parametric formulas for recovering feedback parameters from the acoustic signal are presented. With both feedback loops in place, auditory and somatosensory parameters interact and alter vocal modulations. Model predictions are illustrated in two subjects, one with a diagnosis of multiple sclerosis and intermittent tremor. Findings suggest that phonatory instabilities provide considerable insight into normal and pathogenic changes to the sensorimotor control of voice.

Bottom-up approach to torus bifurcation in neuron models.

We study the quasi-periodicity phenomena occurring at the transition between tonic spiking and bursting activities in exemplary biologically plausible Hodgkin-Huxley type models of individual cells and reduced phenomenological models with slow and fast dynamics. Using the geometric slow-fast dissection and the parameter continuation approach, we show that the transition is due to either the torus bifurcation or the period-doubling bifurcation of a stable periodic orbit on the 2D slow-motion manifold near a characteristic fold. Various torus bifurcations including stable and saddle torus-canards, resonant tori, the co-existence of nested tori, and the torus breakdown leading to the onset of complex and bistable dynamics in such systems are examined too.

Emergent stochastic oscillations and signal detection in tree networks of excitable elements.

We study the stochastic dynamics of strongly-coupled excitable elements on a tree network. The peripheral nodes receive independent random inputs which may induce large spiking events propagating through the branches of the tree and leading to global coherent oscillations in the network. This scenario may be relevant to action potential generation in certain sensory neurons, which possess myelinated distal dendritic tree-like arbors with excitable nodes of Ranvier at peripheral and branching nodes and exhibit noisy periodic sequences of action potentials. We focus on the spiking statistics of the central node, which fires in response to a noisy input at peripheral nodes. We show that, in the strong coupling regime, relevant to myelinated dendritic trees, the spike train statistics can be predicted from an isolated excitable element with rescaled parameters according to the network topology. Furthermore, we show that by varying the network topology the spike train statistics of the central node can be tuned to have a certain firing rate and variability, or to allow for an optimal discrimination of inputs applied at the peripheral nodes.

Noise-induced transitions in a double-well oscillator with nonlinear dissipation.

We develop a model of bistable oscillator with nonlinear dissipation. Using a numerical simulation and an electronic circuit realization of this system we study its response to additive noise excitations. We show that depending on noise intensity the system undergoes multiple qualitative changes in the structure of its steady-state probability density function (PDF). In particular, the PDF exhibits two pitchfork bifurcations versus noise intensity, which we describe using an effective potential and corresponding normal form of the bifurcation. These stochastic effects are explained by the partition of the phase space by the nullclines of the deterministic oscillator.

Emergence and coherence of oscillations in star networks of stochastic excitable elements.

We study the emergence and coherence of stochastic oscillations in star networks of excitable elements in which peripheral nodes receive independent random inputs. A biophysical model of a distal branch of sensory neuron in which peripheral nodes of Ranvier are coupled to a central node by myelinated cable segments is used along with a generic model of networked stochastic active rotators. We show that coherent oscillations can emerge due to stochastic synchronization of peripheral nodes and that the degree of coherence can be maximized by tuning the coupling strength and the size of the network. Analytical results are obtained for the strong-coupling regime of the active rotator network. In particular, we show that in the strong-coupling regime, the network dynamics can be described by an effective single active rotator with rescaled parameters and noise.

Phase Diffusion in Unequally Noisy Coupled Oscillators.

We consider the dynamics of two directionally coupled unequally noisy oscillators, the first oscillator being noisier than the second oscillator. We derive analytically the phase diffusion coefficient of both oscillators in a heterogeneous setup (different frequencies, coupling coefficients, and intrinsic noise intensities) and show that the phase coherence of the second oscillator depends in a nonmonotonic fashion on the noise intensity of the first oscillator: as the first oscillator becomes less coherent, i.e., worse, the second one becomes more coherent, i.e., better. This surprising effect is related to the statistics of the first oscillator which provides a source of noise for the second oscillator, that is non-Gaussian, bounded, and possesses a finite bandwidth. We verify that the effect is robust by numerical simulations of two coupled FitzHugh-Nagumo models.

Stochastic sensitivity analysis of noise-induced suppression of firing and giant variability of spiking in a Hodgkin-Huxley neuron model.

We study the stochastic dynamics of a Hodgkin-Huxley neuron model in a regime of coexistent stable equilibrium and a limit cycle. In this regime, noise may suppress periodic firing by switching the neuron randomly to a quiescent state. We show that at a critical value of the injected current, the mean firing rate depends weakly on noise intensity, while the neuron exhibits giant variability of the interspike intervals and spike count. To reveal the dynamical origin of this noise-induced effect, we develop the stochastic sensitivity analysis and use the Mahalanobis metric for this four-dimensional stochastic dynamical system. We show that the critical point of giant variability corresponds to the matching of the Mahalanobis distances from attractors (stable equilibrium and limit cycle) to a three-dimensional surface separating their basins of attraction.

Effect of bidirectional mechanoelectrical coupling on spontaneous oscillations and sensitivity in a model of hair cells.

Sensory hair cells of amphibians exhibit spontaneous activity in their hair bundles and membrane potentials, reflecting two distinct active amplification mechanisms employed in these peripheral mechanosensors. We use a two-compartment model of the bullfrog's saccular hair cell to study how the interaction between its mechanical and electrical compartments affects the emergence of distinct dynamical regimes, and the role of this interaction in shaping the response of the hair cell to weak mechanical stimuli. The model employs a Hodgkin-Huxley-type system for the basolateral electrical compartment and a nonlinear hair bundle oscillator for the mechanical compartment, which are coupled bidirectionally. In the model, forward coupling is provided by the mechanoelectrical transduction current, flowing from the hair bundle to the cell soma. Backward coupling is due to reverse electromechanical transduction, whereby variations of the membrane potential affect adaptation processes in the hair bundle. We isolate oscillation regions in the parameter space of the model and show that bidirectional coupling affects significantly the dynamics of the cell. In particular, self-sustained oscillations of the hair bundles and membrane potential can result from bidirectional coupling, and the coherence of spontaneous oscillations can be maximized by tuning the coupling strength. Consistent with previous experimental work, the model demonstrates that dynamical regimes of the hair bundle change in response to variations in the conductances of basolateral ion channels. We show that sensitivity of the hair cell to weak mechanical stimuli can be maximized by varying coupling strength, and that stochasticity of the hair bundle compartment is a limiting factor of the sensitivity.

Robust design of polyrhythmic neural circuits.

Neural circuit motifs producing coexistent rhythmic patterns are treated as building blocks of multifunctional neuronal networks. We study the robustness of such a motif of inhibitory model neurons to reliably sustain bursting polyrhythms under random perturbations. Without noise, the exponential stability of each of the coexisting rhythms increases with strengthened synaptic coupling, thus indicating an increased robustness. Conversely, after adding noise we find that noise-induced rhythm switching intensifies if the coupling strength is increased beyond a critical value, indicating a decreased robustness. We analyze this stochastic arrhythmia and develop a generic description of its dynamic mechanism. Based on our mechanistic insight, we show how physiological parameters of neuronal dynamics and network coupling can be balanced to enhance rhythm robustness against noise. Our findings are applicable to a broad class of relaxation-oscillator networks, including Fitzhugh-Nagumo and other Hodgkin-Huxley-type networks.

Noise-induced dispersion and breakup of clusters in cell cycle dynamics.

We study the effects of random perturbations on collective dynamics of a large ensemble of interacting cells in a model of the cell division cycle. We consider a parameter region for which the unperturbed model possesses asymptotically stable two-cluster periodic solutions. Two biologically motivated forms of random perturbations are considered: bounded variations in growth rate and asymmetric division. We compare the effects of these two dispersive mechanisms with additive Gaussian white noise perturbations. We observe three distinct phases of the response to noise in the model. First, for weak noise there is a linear relationship between the applied noise strength and the dispersion of the clusters. Second, for moderate noise strengths the clusters begin to mix, i.e. individual cells move between clusters, yet the population distribution clearly continues to maintain a two-cluster structure. Third, for strong noise the clusters are destroyed and the population is characterized by a uniform distribution. The second and third phases are separated by an order-disorder phase transition that has the characteristics of a Hopf bifurcation. Furthermore, we show that for the cell cycle model studied, the effects of bounded random perturbations are virtually indistinguishable from those induced by additive Gaussian noise, after appropriate scaling of the variance of noise strength. We then use the model to predict the strength of coupling among the cells from experimental data. In particular, we show that coupling must be rather strong to account for the observed clustering of cells given experimentally estimated noise variance.

Characteristic effects of stochastic oscillatory forcing on neural firing: analytical theory and comparison to paddlefish electroreceptor data.

Stochastic signals with pronounced oscillatory components are frequently encountered in neural systems. Input currents to a neuron in the form of stochastic oscillations could be of exogenous origin, e.g. sensory input or synaptic input from a network rhythm. They shape spike firing statistics in a characteristic way, which we explore theoretically in this report. We consider a perfect integrate-and-fire neuron that is stimulated by a constant base current (to drive regular spontaneous firing), along with Gaussian narrow-band noise (a simple example of stochastic oscillations), and a broadband noise. We derive expressions for the nth-order interval distribution, its variance, and the serial correlation coefficients of the interspike intervals (ISIs) and confirm these analytical results by computer simulations. The theory is then applied to experimental data from electroreceptors of paddlefish, which have two distinct types of internal noisy oscillators, one forcing the other. The theory provides an analytical description of their afferent spiking statistics during spontaneous firing, and replicates a pronounced dependence of ISI serial correlation coefficients on the relative frequency of the driving oscillations, and furthermore allows extraction of certain parameters of the intrinsic oscillators embedded in these electroreceptors.

Stochastic sensitivity analysis of the noise-induced excitability in a model of a hair bundle.

We study effect of weak noise on the dynamics of a hair bundle model near the excitability threshold and near a subcritical Hopf bifurcation. We analyze numerically noise-induced structural changes in the probability density and the power spectral density of the model. In particular, we show that weak noise can induce oscillations with two distinct frequencies in both excitable and limit-cycle regimes. We then applied a recently developed technique of stochastic sensitivity functions which allows us to estimate threshold values of noise intensity corresponding to these transitions.

Modelling of photo-thermal control of biological cellular oscillators.

We study the transient dynamics of biological oscillators subjected to brief heat pulses. A prospective well-defined experimental system for thermal control of oscillators is the peripheral electroreceptors in paddlefish. Epithelial cells in these receptors show spontaneous voltage oscillations which are known to be temperature sensitive. We use a computational model to predict the effect of brief thermal pulses in this system. In our model thermal stimulation is realized through the light excitation of gold nanoparticles delivered in close proximity to epithelial cells and generating heat due to plasmon resonance. We use an ensemble of modified Morris-Lecar systems to model oscillatory epithelial cells. First, we validate that the model quantitatively reproduces the dynamics of epithelial oscillations in paddlefish electroreceptors, including responses to static and slow temperature changes. Second, we use the model to predict transient responses to short heat pulses generated by the light actuated gold nanoparticles. The model predicts that the epithelial oscillators can be partially synchronized by brief 5 - 15 ms light stimuli resulting in a large-amplitude oscillations of the mean field potential.

Quantifying utricular stimulation during natural behavior.

The use of natural stimuli in neurophysiological studies has led to significant insights into the encoding strategies used by sensory neurons. To investigate these encoding strategies in vestibular receptors and neurons, we have developed a method for calculating the stimuli delivered to a vestibular organ, the utricle, during natural (unrestrained) behaviors, using the turtle as our experimental preparation. High-speed digital video sequences are used to calculate the dynamic gravito-inertial (GI) vector acting on the head during behavior. X-ray computed tomography (CT) scans are used to determine the orientation of the otoconial layer (OL) of the utricle within the head, and the calculated GI vectors are then rotated into the plane of the OL. Thus, the method allows us to quantify the spatio-temporal structure of stimuli to the OL during natural behaviors. In the future, these waveforms can be used as stimuli in neurophysiological experiments to understand how natural signals are encoded by vestibular receptors and neurons. We provide one example of the method, which shows that turtle feeding behaviors can stimulate the utricle at frequencies higher than those typically used in vestibular studies. This method can be adapted to other species, to other vestibular end organs, and to other methods of quantifying head movements.

Information analysis of posterior canal afferents in the turtle, Trachemys scripta elegans.

We have used sinusoidal and band-limited Gaussian noise stimuli along with information measures to characterize the linear and non-linear responses of morpho-physiologically identified posterior canal (PC) afferents and to examine the relationship between mutual information rate and other physiological parameters. Our major findings are: 1) spike generation in most PC afferents is effectively a stochastic renewal process, and spontaneous discharges are fully characterized by their first order statistics; 2) a regular discharge, as measured by normalized coefficient of variation (cv*), reduces intrinsic noise in afferent discharges at frequencies below the mean firing rate; 3) coherence and mutual information rates, calculated from responses to band-limited Gaussian noise, are jointly determined by gain and intrinsic noise (discharge regularity), the two major determinants of signal to noise ratio in the afferent response; 4) measures of optimal non-linear encoding were only moderately greater than optimal linear encoding, indicating that linear stimulus encoding is limited primarily by internal noise rather than by non-linearities; and 5) a leaky integrate and fire model reproduces these results and supports the suggestion that the combination of high discharge regularity and high discharge rates serves to extend the linear encoding range of afferents to higher frequencies. These results provide a framework for future assessments of afferent encoding of signals generated during natural head movements and for comparison with coding strategies used by other sensory systems. This article is part of a Special Issue entitled: Neural Coding.