We present an optimized conductance-based retina microcircuit simulator which transforms light stimuli into a series of graded and spiking action potentials through photo transduction. We use discrete retinal neuron blocks based on a collation of single-compartment models and morphologically realistic formulations, and successfully achieve a biologically real-time simulator. This is done by optimizing the numerical methods employed to solve the system of over 270 nonlinear ordinary differential equations and parameters. Our simulator includes some of the most recent advances in compartmental modeling to include five intrinsic ion currents of each cell whilst ensuring real-time performance, in attaining the ion-current and membrane responses of the photoreceptor rod and cone cells, the bipolar and amacrine cells, their laterally connected electrical and chemical synapses, and the output ganglion cell. It exhibits dynamical retinal behavior such as spike-frequency adaptation, rebound activation, fast-spiking, and subthreshold responsivity. Light stimuli incident at the photoreceptor rod and cone cells is modulated through the system of differential equations, enabling the user to probe the neuronal response at any point in the network. This is in contrast to many other retina encoding schemes which prefer to `black-box' the preceding stages to the spike train output. Our simulator is made available open source, with the hope that it will benefit neuroscientists and machine learning practitioners in better understanding the retina sub-circuitries, how retina cells optimize the representation of visual information, and in generating large datasets of biologically accurate graded and spiking responses.
Neuronal spiking exhibits an exquisite combination of modulation and robustness properties, rarely matched in artificial systems. We exploit the particular interconnection structure of conductance based models to investigate this remarkable property. We find that much of neuronal modulation and robustness can be explained by separating the total transmembrane current into three different components corresponding to the three time scales of neuronal bursting. Each equivalent current aggregates many ionic contributions into an equivalent voltage-dependent conductance, which defines a key modulat…
Biological systems are notoriously noisy. Noise, therefore, also plays an important role in many models of neural impulse generation. Noise is not only introduced for more realistic simulations but also to account for cooperative effects between noisy and nonlinear dynamics. Often, this is achieved by a simple noise term in the membrane equation (current noise). However, there are ongoing discussions whether such current noise is justified or whether rather conductance noise should be introduced because it is closer to the natural origin of noise. Therefore, we have compared the effects of cur…
Reduced models of neuronal activity such as Integrate-and-Fire models allow a description of neuronal dynamics in simple, intuitive terms and are easy to simulate numerically. We present a method to fit an Integrate-and-Fire-type model of neuronal activity, namely a modified version of the Spike Response Model, to a detailed Hodgkin-Huxley-type neuron model driven by stochastic spike arrival. In the Hogkin-Huxley model, spike arrival at the synapse is modeled by a change of synaptic conductance. For such conductance spike input, more than 70% of the postsynaptic action potentials can be predic…
The interaction between excitation and inhibition is crucial for brain computation. To understand synaptic mechanisms underlying brain function, it is important to separate excitatory and inhibitory inputs to a target neuron. In the traditional method, after applying somatic current or voltage clamp, the excitatory and inhibitory conductances are determined from the synaptic current-voltage (I-V) relation --- the slope corresponds to the total conductance and the intercept corresponds to the reversal current. Because of the space clamp effect, the measured conductance in general deviates subst…
We study the time delay in the synaptic conductance for suppression of spike synchronisation in a random network of Hodgkin Huxley neurons coupled by means of chemical synapses. In the first part, we examine in detail how the time delay acts over the network during the synchronised and desynchronised neuronal activities. We observe a relation between the neuronal dynamics and the syaptic conductance distributions. We find parameter values in which the time delay has high effectiveness in promoting the suppression of spike synchronisation. In the second part, we analyse how the delayed neuronal…
We use the qualitative insight of a planar neuronal phase portrait to detect an excitability switch in arbitrary conductance-based models from a simple mathematical condition. The condition expresses a balance between ion channels that provide a negative feedback at resting potential (restorative channels) and those that provide a positive feedback at resting potential (regenerative channels). Geometrically, the condition imposes a transcritical bifurcation that rules the switch of excitability through the variation of a single physiological parameter. Our analysis of six different published c…
We investigate the stimulus-dependent tuning properties of a noisy ionic conductance model for intrinsic subthreshold oscillations in membrane potential and associated spike generation. On depolarization by an applied current, the model exhibits subthreshold oscillatory activity with occasional spike generation when oscillations reach the spike threshold. We consider how the amount of applied current, the noise intensity, variation of maximum conductance values and scaling to different temperature ranges alter the responses of the model with respect to voltage traces, interspike intervals and …
Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the last decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of active dendritic trees is a highly non-linear function of their afferent rate, attaining extremely large dynamic…
Centre for Theoretical Neuroscience, University of Waterloo（滑铁卢大学理论神经科学中心）
The mathematical model underlying the Neural Engineering Framework (NEF) expresses neuronal input as a linear combination of synaptic currents. However, in biology, synapses are not perfect current sources and are thus nonlinear. Detailed synapse models are based on channel conductances instead of currents, which require independent handling of excitatory and inhibitory synapses. This, in particular, significantly affects the influence of inhibitory signals on the neuronal dynamics. In this technical report we first summarize the relevant portions of the NEF and conductance-based synapse model…
We review two examples where the linear response of a neuronal network submitted to an external stimulus can be derived explicitely, including network parameters dependence. This is done in a statistical physics-like approach where one associates to the spontaneous dynamics of the model a natural notion of Gibbs distribution inherited from ergodic theory or stochastic processes. These two examples are the Amari-Wilson-Cowan model and a conductance based Integrate and Fire model.
The temporal dynamics of membrane voltage changes in neurons is controlled by ionic currents. These currents are characterized by two main properties: conductance and kinetics. The hyperpolarization-activated current ($I_{\rm h}$) strongly modulates subthreshold potential changes by shortening the excitatory postsynaptic potentials and decreasing their temporal summation. Whereas the shortening of the synaptic potentials caused by the $I_{\rm h}$ conductance is well understood, the role of the $I_{\rm h}$ kinetics remains unclear. Here, we use a model of the $I_{\rm h}$ current model with eith…
Networks of excitatory and inhibitory neurons display asynchronous irregular (AI) states, where the activities of the two populations are balanced. At the single cell level, it was shown that neurons subject to balanced and noisy synaptic inputs can display enhanced responsiveness. We show here that this enhanced responsiveness is also present at the network level, but only when single neurons are in a conductance state and fluctuation regime consistent with experimental measurements. In such states, the entire population of neurons is globally influenced by the external input. We suggest that…
Strong inhibitory input to neurons, which occurs in balanced states of neural networks, increases synaptic current fluctuations. This has led to the assumption that inhibition contributes to the high spike-firing irregularity observed in vivo. We used single compartment neuronal models with time-correlated (due to synaptic filtering) and state-dependent (due to reversal potentials) input to demonstrate that inhibitory input acts to decrease membrane potential fluctuations, a result that cannot be achieved with simplified neural input models. To clarify the effects on spike-firing regularity, w…
Measured responses from visual cortical neurons show that spike times tend to be correlated rather than exactly Poisson distributed. Fano factors vary and are usually greater than 1 due to the tendency of spikes being clustered into bursts. We show that this behavior emerges naturally in a balanced cortical network model with random connectivity and conductance-based synapses. We employ mean field theory with correctly colored noise to describe temporal correlations in the neuronal activity. Our results illuminate the connection between two independent experimental findings: high conductance s…
We discuss synchronization in networks of neuronal oscillators which are interconnected via diffusive coupling, i.e. linearly coupled via gap junctions. In particular, we present sufficient conditions for synchronization in these networks using the theory of semi-passive and passive systems. We show that the conductance-based neuronal models of Hodgkin-Huxley, Morris-Lecar, and the popular reduced models of FitzHugh-Nagumo and Hindmarsh-Rose all satisfy a semi-passivity property, i.e. that is the state trajectories of such a model remain oscillatory but bounded provided that the supplied (elec…
By controlling the state of neuronal populations, neuromodulators ultimately affect behaviour. A key neuromodulation mechanism is the alteration of neuronal excitability via the modulation of ion channel expression. This type of neuromodulation is normally studied via conductance-based models, but those models are computationally challenging for large-scale network simulations needed in population studies. This paper studies the modulation properties of the Multi-Quadratic Integrate-and-Fire (MQIF) model, a generalisation of the classical Quadratic Integrate-and-Fire (QIF) model. The model is …
We investigate the effect of electric synapses (gap junctions) on collective neuronal dynamics and spike statistics in a conductance-based Integrate-and-Fire neural network, driven by a Brownian noise, where conductances depend upon spike history. We compute explicitly the time evolution operator and show that, given the spike-history of the network and the membrane potentials at a given time, the further dynamical evolution can be written in a closed form. We show that spike train statistics is described by a Gibbs distribution whose potential can be approximated with an explicit formula, whe…
Demystifying effective connectivity among neuronal populations has become the trend to understand the brain mechanisms of Parkinson's disease, schizophrenia, mild traumatic brain injury, and many other unlisted neurological diseases. Dynamic modeling is a state-of-the-art approach to explore various connectivities among neuronal populations corresponding to different electrophysiological responses. Through estimating the parameters in the dynamic models, including the strengths and propagation delays of the electrophysiological signals, the discovery of the underlying connectivities can lead t…
In this paper we provide two representations for stochastic ion channel kinetics, and compare the performance of exact simulation with a commonly used numerical approximation strategy. The first representation we present is a random time change representation, popularized by Thomas Kurtz, with the second being analogous to a "Gillespie" representation. Exact stochastic algorithms are provided for the different representations, which are preferable to either (a) fixed time step or (b) piecewise constant propensity algorithms, which still appear in the literature. As examples, we provide version…
Many types of neurons exhibit spike rate adaptation, mediated by intrinsic slow $\mathrm{K}^+$-currents, which effectively inhibit neuronal responses. How these adaptation currents change the relationship between in-vivo like fluctuating synaptic input, spike rate output and the spike train statistics, however, is not well understood. In this computational study we show that an adaptation current which primarily depends on the subthreshold membrane voltage changes the neuronal input-output relationship (I-O curve) subtractively, thereby increasing the response threshold. A spike-dependent adap…
It is well known that Electroencephalography(EEG) and the respective evoked potentials have deep implications corresponding to specific cognitive tasks and in the diagnosis of several diseases such as epilepsy and schizophrenia. Some recent experimental results have already shown some evidence of chaotic activity in the brain. The Hodgekin-Huxley(HH) models, may yield geometrical solutions in terms of limit cycles and basins of attractors, but its implementation requires a priori knowledge of the kinetics of the innumerable conductances acting in a given set of cells. We are of the opinion tha…
We investigate different dynamical regimes of neuronal network in the CA3 area of the hippocampus. The proposed neuronal circuit includes two fast- and two slowly-spiking cells which are interconnected by means of dynamical synapses. On the individual level, each neuron is modeled by FitzHugh-Nagumo equations. Three basic rhythmic patterns are observed: gamma-rhythm in which the fast neurons are uniformly spiking, theta-rhythm in which the individual spikes are separated by quiet epochs, and theta/gamma rhythm with repeated patches of spikes. We analyze the influence of asymmetry of synaptic s…
Complex systems in the real world can be modeled as a network of connected components. The human brain, as a network of neurons among which the interactions cause perception, is a complex network. Synchronization is a dynamical phenomenon that can be seen in the brain. The network topology has a remarkable impact on both the function and the dynamics of neural networks. In this research, synchronization of neural networks is scrutinized through creating various topologies. These networks include both excitatory and inhibitory neurons. We investigate the dynamics of different networks by random…
Intracellular recordings of neuronal membrane potential are a central tool in neurophysiology. In many situations, especially in vivo, the traditional limitation of such recordings is the high electrode resistance, which may cause significant measurement errors. We introduce a computer-aided technique, Active Electrode Compensation (AEC), based on a digital model of the electrode interfaced in real time with the electrophysiological setup. The characteristics of this model are first estimated using white noise current injection. The electrode and membrane contribution are digitally separated, …
Synaptic delays modulate population phase and amplitude responses in oscillatory excitatory-inhibitory networks
Institute for Advanced Studies in Basic Sciences (IASBS)（基础科学高等研究院）；Institute for Research in Fundamental Sciences (IPM)（基本科学研究院）；Pasargad Institute for Advanced Innovative Solutions (PIAIS)（帕萨尔加德先进创新解决方案研究所）；The Zapata-Briceño Institute of Neuroscience（萨帕塔-布里斯尼奥神经科学研究所）
While spike timing has been shown to carry detailed stimulus information at the sensory periphery, its possible role in network computation is less clear. Most models of computation by neural networks are based on population firing rates. In equivalent spiking implementations, firing is assumed to be random such that averaging across populations of neurons recovers the rate-based approach. Recently, however, Denéve and colleagues have suggested that the spiking behavior of neurons may be fundamental to how neuronal networks compute, with precise spike timing determined by each neuron's contrib…
High-level brain function such as memory, classification or reasoning can be realized by means of recurrent networks of simplified model neurons. Analog neuromorphic hardware constitutes a fast and energy efficient substrate for the implementation of such neural computing architectures in technical applications and neuroscientific research. The functional performance of neural networks is often critically dependent on the level of correlations in the neural activity. In finite networks, correlations are typically inevitable due to shared presynaptic input. Recent theoretical studies have shown…
