Publications

Bottom-up models of functionally relevant patterns of neural activity provide an explicit link between neuronal dynamics and computation. A prime example of functional activity pattern is hippocampal replay, which is critical for memory consolidation. The switchings between replay events and a low-activity state in neural recordings suggests metastable neural circuit dynamics. As metastability has been attributed to noise and/or slow fatigue mechanisms, we propose a concise mesoscopic model which accounts for both. Crucially, our model is bottom-up: it is analytically derived from the dynamics of finite-size networks of Linear-Nonlinear Poisson neurons with short-term synaptic depression. As such, noise is explicitly linked to spike noise and network size, and fatigue is explicitly linked to synaptic dynamics. To derive the mesosocpic model, we first consider a homogeneous spiking neural network and follow the temporal coarse-graining approach of Gillespie ("chemical Langevin equation"), which can be naturally interpreted as a stochastic neural mass model. The Langevin equation is computationally inexpensive to simulate and enables a thorough study of metastable dynamics in classical setups (population spikes and Up-Down states dynamics) by means of phase-plane analysis. This stochastic neural mass model is the basic component of our mesoscopic model for replay. We show that our model faithfully captures the stochastic nature of individual replayed trajectories. Moreover, compared to the deterministic Romani-Tsodyks model of place cell dynamics, it exhibits a higher level of variability in terms of content, direction and timing of replay events, compatible with biological evidence and could be functionally desirable. This variability is the product of a new dynamical regime where metastability emerges from a complex interplay between finite-size fluctuations and local fatigue.

Assemblies of neurons, called concepts cells, encode acquired concepts in human Medial Temporal Lobe. Those concept cells that are shared between two assemblies have been hypothesized to encode associations between concepts. Here we test this hypothesis in a computational model of attractor neural networks. We find that for concepts encoded in sparse neural assemblies there is a minimal fraction cmin of neurons shared between assemblies below which associations cannot be reliably implemented; and a maximal fraction cmax of shared neurons above which single concepts can no longer be retrieved. In the presence of a periodically modulated background signal, such as hippocampal oscillations, recall takes the form of association chains reminiscent of those postulated by theories of free recall of words. Predictions of an iterative overlap-generating model match experimental data on the number of concepts to which a neuron responds.

Noise in spiking neurons is commonly modeled by a noisy input current or by generating output spikes stochastically with a voltage-dependent hazard rate (“escape noise”). While input noise lends itself to modeling biophysical noise processes, the phenomenological escape noise is mathematically more tractable. Using the level-crossing theory for differentiable Gaussian processes, we derive an approximate mapping between colored input noise and escape noise in leaky integrate-and-fire neurons. This mapping requires the first-passage-time (FPT) density of an overdamped Brownian particle driven by colored noise with respect to an arbitrarily moving boundary. Starting from the Wiener–Rice series for the FPT density, we apply the second-order decoupling approximation of Stratonovich to the case of moving boundaries and derive a simplified hazard-rate representation that is local in time and numerically efficient. This simplification requires the calculation of the non-stationary auto-correlation function of the level-crossing process: For exponentially correlated input noise (Ornstein–Uhlenbeck process), we obtain an exact formula for the zero-lag auto-correlation as a function of noise parameters, mean membrane potential and its speed, as well as an exponential approximation of the full auto-correlation function. The theory well predicts the FPT and interspike interval densities as well as the population activities obtained from simulations with colored input noise and time-dependent stimulus or boundary. The agreement with simulations is strongly enhanced across the sub- and suprathreshold firing regime compared to a first-order decoupling approximation that neglects correlations between level crossings. The second-order approximation also improves upon a previously proposed theory in the subthreshold regime. Depending on a simplicity-accuracy trade-off, all considered approximations represent useful mappings from colored input noise to escape noise, enabling progress in the theory of neuronal population dynamics.

Population equations for infinitely large networks of spiking neurons have a long tradition in theoretical neuroscience. In this work, we analyze a recent generalization of these equations to populations of finite size, which takes the form of a nonlinear stochastic integral equation. We prove that, in the case of leaky integrate-and-fire (LIF) neurons with escape noise and for a slightly simplified version of the model, the equation is well-posed and stable in the sense of Brémaud-Massoulié. The proof combines methods from Markov processes taking values in the space of positive measures and nonlinear Hawkes processes. For applications, we also provide an efficient simulation algorithm for interacting populations of LIF neurons.

The macroscopic dynamics of large populations of neurons can be mathematically analyzed using low-dimensional firing-rate or neural-mass models. However, these models fail to capture spike synchronization effects and nonstationary responses of the population activity to rapidly changing stimuli. Here we derive low-dimensional firing-rate models for homogeneous populations of neurons modeled as time-dependent renewal processes. The class of renewal neurons includes integrate-and-fire models driven by white noise and has been frequently used to model neuronal refractoriness and spike synchronization dynamics. The derivation is based on an eigenmode expansion of the associated refractory density equation, which generalizes previous spectral methods for Fokker-Planck equations to arbitrary renewal models. We find a simple relation between the eigenvalues characterizing the timescales of the firing rate dynamics and the Laplace transform of the interspike interval density, for which explicit expressions are available for many renewal models. Retaining only the first eigenmode already yields a reliable low-dimensional approximation of the firing-rate dynamics that captures spike synchronization effects and fast transient dynamics at stimulus onset. We explicitly demonstrate the validity of our model for a large homogeneous population of Poisson neurons with absolute refractoriness and other renewal models that admit an explicit analytical calculation of the eigenvalues. The eigenmode expansion presented here provides a systematic framework for alternative firing-rate models in computational neuroscience based on spiking neuron dynamics with refractoriness.

Coarse-graining microscopic models of biological neural networks to obtain mesoscopic models of neural activities is an essential step towards multi-scale models of the brain. Here, we extend a recent theory for mesoscopic population dynamics with static synapses to the case of dynamic synapses exhibiting short-term plasticity (STP). The extended theory offers an approximate mean-field dynamics for the synaptic input currents arising from populations of spiking neurons and synapses undergoing Tsodyks–Markram STP. The approximate mean-field dynamics accounts for both finite number of synapses and correlation between the two synaptic variables of the model (utilization and available resources) and its numerical implementation is simple. Comparisons with Monte Carlo simulations of the microscopic model show that in both feedforward and recurrent networks, the mesoscopic mean-field model accurately reproduces the first- and second-order statistics of the total synaptic input into a postsynaptic neuron and accounts for stochastic switches between Up and Down states and for population spikes. The extended mesoscopic population theory of spiking neural networks with STP may be useful for a systematic reduction of detailed biophysical models of cortical microcircuits to numerically efficient and mathematically tractable mean-field models.

The dominant modeling framework for understanding cortical computations are heuristic firing rate models. Despite their success, these models fall short to capture spike synchronization effects, to link to biophysical parameters and to describe finite-size fluctuations. In this opinion article, we propose that the refractory density method (RDM), also known as age-structured population dynamics or quasi-renewal theory, yields a powerful theoretical framework to build rate-based models for mesoscopic neural populations from realistic neuron dynamics at the microscopic level. We review recent advances achieved by the RDM to obtain efficient population density equations for networks of generalized integrate-and-fire (GIF) neurons – a class of neuron models that has been successfully fitted to various cell types. The theory not only predicts the nonstationary dynamics of large populations of neurons but also permits an extension to finite-size populations and a systematic reduction to low-dimensional rate dynamics. The new types of rate models will allow a re-examination of models of cortical computations under biological constraints.

Author summary Biological neural networks are formed by a large number of neurons whose interactions can be extremely complex. Such systems have been successfully studied using random network models, in which the interactions among neurons are assumed to be random. However, the dynamics of single units are usually described using over-simplified models, which might not capture several salient features of real neurons. Here, we show how accounting for richer single-neuron dynamics results in shaping the network dynamics and determines which signals are better transmitted. We focus on adaptation, an important mechanism present in biological neurons that consists in the decrease of their firing rate in response to a sustained stimulus. Our mean-field approach reveals that the presence of adaptation shifts the network into a previously unreported dynamical regime, that we term “resonant chaos”, in which chaotic activity has a strong oscillatory component. Moreover, we show that this regime is advantageous for the transmission of low-frequency signals. Our work bridges the microscopic dynamics (single neurons) to the macroscopic dynamics (network), and shows how the global signal-transmission properties of the network can be controlled by acting on the single-neuron dynamics. These results paves the way for further developments that include more complex neural mechanisms, and considerably advance our understanding of realistic neural networks.

Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50 – 2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations.

Reconsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of synaptic consolidation to capture hippocampal slice experiments that have been interpreted as reconsolidation at the synaptic level. The model implements reconsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI). We derive a reduced version of our model to explore the conditions under which synaptic reconsolidation does or does not occur, often referred to as the boundary conditions of reconsolidation. We find that our computational model of synaptic reconsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of synaptic reconsolidation.

The calculation of the steady-state probability density for multidimensional stochastic systems that do not obey detailed balance is a difficult problem. Here we present the analytical derivation of the stationary joint and various marginal probability densities for a stochastic neuron model with adaptation current. Our approach assumes weak noise but is valid for arbitrary adaptation strength and time scale. The theory predicts several effects of adaptation on the statistics of the membrane potential of a tonically firing neuron: (i) a membrane potential distribution with a convex shape, (ii) a strongly increased probability of hyperpolarized membrane potentials induced by strong and fast adaptation, and (iii) a maximized variability associated with the adaptation current at a finite adaptation time scale.

Nerve cells in the brain generate sequences of action potentials with a complex statistics. Theoretical attempts to understand this statistics were largely limited to the case of a temporally uncorrelated input (Poissonian shot noise) from the neurons in the surrounding network. However, the stimulation from thousands of other neurons has various sorts of temporal structure. Firstly, input spike trains are temporally correlated because their firing rates can carry complex signals and because of cell-intrinsic properties like neural refractoriness, bursting, or adaptation. Secondly, at the connections between neurons, the synapses, usage-dependent changes in the synaptic weight (short-term plasticity) further shape the correlation structure of the effective input to the cell. From the theoretical side, it is poorly understood how these correlated stimuli, so-called colored noise, affect the spike train statistics. In particular, no standard method exists to solve the associated first-passage-time problem for the interspike-interval statistics with an arbitrarily colored noise. Assuming that input fluctuations are weaker than the mean neuronal drive, we derive simple formulas for the essential interspike-interval statistics for a canonical model of a tonically firing neuron subjected to arbitrarily correlated input from the network. We verify our theory by numerical simulations for three paradigmatic situations that lead to input correlations: (i) rate-coded naturalistic stimuli in presynaptic spike trains; (ii) presynaptic refractoriness or bursting; (iii) synaptic short-term plasticity. In all cases, we find severe effects on interval statistics. Our results provide a framework for the interpretation of firing statistics measured in vivo in the brain.

Networks of fast nonlinear elements may display slow fluctuations if interactions are strong. We find a transition in the long-term variability of a sparse recurrent network of perfect integrate-and-fire neurons at which the Fano factor switches from zero to infinity and the correlation time is minimized. This corresponds to a bifurcation in a linear map arising from the self-consistency of temporal input and output statistics. More realistic neural dynamics with a leak current and refractory period lead to smoothed transitions and modified critical couplings that can be theoretically predicted.

We study the spike statistics of an adaptive exponential integrate-and-fire neuron stimulated by white Gaussian current noise. We derive analytical approximations for the coefficient of variation and the serial correlation coefficient of the interspike interval assuming that the neuron operates in the mean-driven tonic firing regime and that the stochastic input is weak. Our result for the serial correlation coefficient has the form of a geometric sequence and is confirmed by the comparison to numerical simulations. The theory predicts various patterns of interval correlations (positive or negative at lag one, monotonically decreasing or oscillating) depending on the strength of the spike-triggered and subthreshold components of the adaptation current. In particular, for pure subthreshold adaptation we find strong positive ISI correlations that are usually ascribed to positive correlations in the input current. Our results i) provide an alternative explanation for interspike-interval correlations observed in vivo, ii) may be useful in fitting point neuron models to experimental data, and iii) may be instrumental in exploring the role of adaptation currents for signal detection and signal transmission in single neurons.

Finite-sized populations of spiking elements are fundamental to brain function but also are used in many areas of physics. Here we present a theory of the dynamics of finite-sized populations of spiking units, based on a quasirenewal description of neurons with adaptation. We derive an integral equation with colored noise that governs the stochastic dynamics of the population activity in response to time-dependent stimulation and calculate the spectral density in the asynchronous state. We show that systems of coupled populations with adaptation can generate a frequency band in which sensory information is preferentially encoded. The theory is applicable to fully as well as randomly connected networks and to leaky integrate-and-fire as well as to generalized spiking neurons with adaptation on multiple time scales.

Neural firing is often subject to negative feedback by adaptation currents. These currents can induce strong correlations among the time intervals between spikes. Here we study analytically the interval correlations of a broad class of noisy neural oscillators with spike-triggered adaptation of arbitrary strength and time scale. Our weak-noise theory provides a general relation between the correlations and the phase-response curve (PRC) of the oscillator, proves anti-correlations between neighboring intervals for adapting neurons with type I PRC and identifies a single order parameter that determines the qualitative pattern of correlations. Monotonically decaying or oscillating correlation structures can be related to qualitatively different voltage traces after spiking, which can be explained by the phase plane geometry. At high firing rates, the long-term variability of the spike train associated with the cumulative interval correlations becomes small, independent of model details. Our results are verified by comparison with stochastic simulations of the exponential, leaky, and generalized integrate-and-fire models with adaptation.

Sequences of first-passage times can describe the interspike intervals (ISI) between subsequent action potentials of sensory neurons. Here, we consider the ISI statistics of a stochastic neuron model, a leaky integrate-and-fire neuron, which is driven by a strong mean input current, white Gaussian current noise, and a spike-frequency adaptation current. In previous studies, it has been shown that without a leak current, i.e. for a so-called perfect integrate-and-fire (PIF) neuron, the ISI density can be well approximated by an inverse Gaussian corresponding to the first-passage-time density of a biased random walk. Furthermore, the serial correlations between ISIs, which are induced by the adaptation current, can be described by a geometric series. By means of stochastic simulations, we inspect whether these results hold true in the presence of a modest leak current. Specifically, we measure mean and variance of the ISI in the full model with leak and use the analytical results for the perfect IF model to relate these cumulants of the ISI to effective values of the mean input and noise intensity of an equivalent perfect IF model. This renormalization procedure yields semi-analytical approximations for the ISI density and the ISI serial correlation coeffcient in the full model with leak. We find that both in the absence and the presence of an adaptation current, the ISI density can be well approximated in this way if the leak current constitutes only a weak modification of the dynamics. Moreover, also the serial correlations of the model with leak are well reproduced by the expressions for a PIF model with renormalized parameters. Our results explain, why expressions derived for the rather special perfect integrate-and-fire model can nevertheless be often well fit to experimental 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.

Signals from different sensory modalities may converge on a single neuron. We study theoretically a setup in which one signal is transmitted via facilitating synapses (F signal) and another via depressing synapses (D signal). When both signals are present, the postsynaptic cell preferentially encodes information about slow components of the F signal and fast components of the D signal, whereas for a single signal, transmission is broadband. We also show that, in the fluctuation-driven regime, the rate of information transmission may be increased through stochastic resonance (SR). Remarkably, the role of the beneficial noise is played by another signal, which is itself represented in the spike train of the postsynaptic cell.

We study correlations of intervals between pulses in an excitable system, using a semiconductor laser with optical feedback as an experimental model system. First we show, by means of a combination of experimental observations and theoretical analysis, that for an intermediate range of the laser’s pump current the interspike intervals are positively correlated over a few lags, an effect that can be theoretically explained by an intrinsic two-state switching in the laser dynamics. The same theory can be also applied if the laser is externally driven by a dichotomous switching of the pump current, a scenario that allows for a controlled change of the spike rates of the two states over orders of magnitude. Varying one of the pump levels, we find experimentally that the correlation between adjacent intervals is maximized at a finite pump level corresponding to an optimal ratio of dropout rates in the two states. Our theory confirms these findings and reveals how the regularity of spiking in the two states shapes the correlation maximum.

Spike-timing variability has a large effect on neural information processing. However, for many systems little is known about the noise sources causing the spike-response variability. Here we investigate potential sources of spike-response variability in auditory receptor neurons of locusts, a classic insect model system. At low-spike frequencies, our data show negative interspike-interval (ISI) correlations and ISI distributions that match the inverse Gaussian distribution. These findings can be explained by a white-noise source that interacts with an adaptation current. At higher spike frequencies, more strongly peaked distributions and positive ISI correlations appear, as expected from a canonical model of suprathreshold firing driven by temporally correlated (i.e., colored) noise. Simulations of a minimal conductance-based model of the auditory receptor neuron with stochastic ion channels exclude the delayed rectifier as a possible noise source. Our analysis suggests channel noise from an adaptation current and the receptor or sodium current as main sources for the colored and white noise, respectively. By comparing the ISI statistics with generic models, we find strong evidence for two distinct noise sources. Our approach does not involve any dendritic or somatic recordings that may harm the delicate workings of many sensory systems. It could be applied to various other types of neurons, in which channel noise dominates the fluctuations that shape the neuron’s spike statistics.

Active Brownian particles (ABPs), obeying a nonlinear Langevin equation with speed-dependent drift and noise amplitude, are well-known models used to describe self-propelled motion in biology. In this paper we study a model describing the stochastic dynamics of a group of coupled molecular motors (CMMs). Using two independent numerical methods, one based on the stationary velocity distribution of the motors and the other one on the local increments (also known as the Kramers-Moyal coefficients) of the velocity, we establish a connection between the CMM and the ABP models. The parameters extracted for the ABP via the two methods show good agreement for both symmetric and asymmetric cases and are independent of N, the number of motors, provided that N is not too small. This indicates that one can indeed describe the CMM problem with a simpler ABP model. However, the power spectrum of velocity fluctuations in the CMM model reveals a peak at a finite frequency, a peak which is absent in the velocity spectrum of the ABP model. This implies richer dynamic features of the CMM model which cannot be captured by an ABP model.

We consider stochastic systems with m internal states in which discrete events (e.g. hopping events between metastable states or firing events of neurons) occur at a state-dependent rate. Transitions between states are possible with certain fixed rates. Because the state immediately after an event depends in general on the history of the process, the intervals between two consecutive events (“residence times”) are correlated among each other, i.e. the residence time sequence constitutes a nonrenewal process. We construct a general kinetic scheme that accounts for the number of events at a given time. The count statistics is used to derive a general expression for the correlation coefficient of residence times with a certain lag. We apply the theoretical result to a simple neuron model with discrete threshold states leading to negative interspike interval correlations.

Channel noise is the dominant intrinsic noise source of neurons causing variability in the timing of action potentials and interspike intervals (ISI). Slow adaptation currents are observed in many cells and strongly shape response properties of neurons. These currents are mediated by finite populations of ionic channels and may thus carry a substantial noise component. Here we study the effect of such adaptation noise on the ISI statistics of an integrate-and-fire model neuron by means of analytical techniques and extensive numerical simulations. We contrast this stochastic adaptation with the commonly studied case of a fast fluctuating current noise and a deterministic adaptation current (corresponding to an infinite population of adaptation channels). We derive analytical approximations for the ISI density and ISI serial correlation coefficient for both cases. For fast fluctuations and deterministic adaptation, the ISI density is well approximated by an inverse Gaussian (IG) and the ISI correlations are negative. In marked contrast, for stochastic adaptation, the density is more peaked and has a heavier tail than an IG density and the serial correlations are positive. A numerical study of the mixed case where both fast fluctuations and adaptation channel noise are present reveals a smooth transition between the analytically tractable limiting cases. Our conclusions are furthermore supported by numerical simulations of a biophysically more realistic Hodgkin-Huxley type model. Our results could be used to infer the dominant source of noise in neurons from their ISI statistics.

Exact expressions for first- and higher-order residence time statistics, count statistics, and spectral properties of a bistable system driven by dichotomous colored noise are put forward and discussed. The employed method is based on a discrete kinetic scheme and is valid for a wide range of parameter values of the colored noise. This permits a detailed analysis of the effects of noise correlations for arbitrary correlation times. It is found that at a characteristic correlation time of the dichotomous noise, the residence time sequence becomes Poissonian; in particular, all correlations between residence times disappear. We also find that correlations become strongest for a finite strength of the driving force. The analytical results can also be used to infer the underlying driving parameters in the case of noise with long-range temporal correlations.

We analytically investigate the interspike interval (ISI) density, the Fano factor, and the coefficient of variation of a leaky integrate-and-fire neuron model driven by exponentially correlated Gaussian noise with a large correlation time τ. We find a burstinglike behavior of the spike train, which is revealed by a dominant peak of the ISI density at small intraburst intervals and a slow power-law decay of long interburst intervals. The large, power-law distributed ISIs give rise to a coefficient of variation which diverges as √τ. This leads to the paradoxical effect that ISI correlations, as expressed by the serial correlation coefficient, vanish for large correlation times. This is in contrast to findings of previous works on a simpler neuron model where the effect of noise correlations appeared in higher-order statistical measures.

Sequences of residence times (RTs) associated with the escape from metastable states are observed in many fields. Here we study analytically and numerically the correlations among RTs for a bistable stochastic system driven by dichotomous noise. Our theory predicts an oscillatory behavior of the correlations with respect to the lag between RTs. Correlations vanish at all lags if the switching rate matches the hopping rate of the unperturbed system. It is also shown that RT correlations may reveal features of the driving which are not present in the single-RT statistics.

Great success and profit of the chaos suppression phenomenon in applications led to the widespread opinion that chaotic oscillations may always be stabilized by parametric perturbations. Nevertheless, in what cases can the chaos be suppressed in such a manner? In general, this question means that we should perturb the system within a region of parameter values where chaotic behavior occurs. The chaoticity region may be determined as a set of parameters for which the separatrices are split. In this case, the maximal Lyapunov exponent is always positive. Thus, the chaos suppression implies that all perturbed parameters should not fall outside the limits of this region. In the present paper, by a Duffing-Holmes system we construct an analytic example when parametric perturbations cannot lead to the suppression of chaos if they belong to the chaoticity region. One can expect that the same results may be observed in the other physical systems. Our analysis is based on the Melnikov method, which gives us a criterion for the observation of chaos. The obtained results are in excellent agreement with numerical simulations.