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Biologically detailed models of brain circuitry are challenging to build and simulate due to the large number of neurons, their complex interactions, and the many unknown physiological parameters. Simplified mathematical models are more tractable, but harder to evaluate when too far removed from neuroanatomy/physiology. We propose that a multiscale model, coarse-grained (CG) while preserving local biological details, offers the best balance between biological realism and computability. This paper presents such a model. Generally, CG models focus on the interaction between groups of neurons-here termed "pixels"-rather than individual cells. In our case, dynamics are alternately updated at intra- and interpixel scales, with one informing the other, until convergence to equilibrium is achieved on both scales. An innovation is how we exploit the underlying biology: Taking advantage of the similarity in local anatomical structures across large regions of the cortex, we model intrapixel dynamics as a single dynamical system driven by "external" inputs. These inputs vary with events external to the pixel, but their ranges can be estimated a priori . Precomputing and tabulating all potential local responses speed up the updating procedure significantly compared to direct multiscale simulation. We illustrate our methodology using a model of the primate visual cortex. Except for local neuron-to-neuron variability (necessarily lost in any CG approximation) our model reproduces various features of large-scale network models at a tiny fraction of the computational cost. These include neuronal responses as a consequence of their orientation selectivity, a primary function of visual neurons., Competing Interests: Competing interests statement:The authors declare no competing interest.

In neuroscience, computational modeling is an effective way to gain insight into cortical mechanisms, yet the construction and analysis of large-scale network models-not to mention the extraction of underlying principles-are themselves challenging tasks, due to the absence of suitable analytical tools and the prohibitive costs of systematic numerical exploration of high-dimensional parameter spaces. In this paper, we propose a data-driven approach assisted by deep neural networks (DNN). The idea is to first discover certain input-output relations, and then to leverage this information and the superior computation speeds of the well-trained DNN to guide parameter searches and to deduce theoretical understanding. To illustrate this novel approach, we used as a test case a medium-size network of integrate-and-fire neurons intended to model local cortical circuits. With the help of an accurate yet extremely efficient DNN surrogate, we revealed the statistics of model responses, providing a detailed picture of model behavior. The information obtained is both general and of a fundamental nature, with direct application to neuroscience. Our results suggest that the methodology proposed can be scaled up to larger and more complex biological networks when used in conjunction with other techniques of biological modeling.

This paper introduces a class of stochastic models of interacting neurons with emergent dynamics similar to those seen in local cortical populations. Rigorous results on existence and uniqueness of nonequilibrium steady states are proved. These network models are then compared to very simple reduced models driven by the same mean excitatory and inhibitory currents. Discrepancies in firing rates between network and reduced models are investigated and explained by correlations in spiking, or partial synchronization, working in concert with "nonlinearities" in the time evolution of membrane potentials. The use of simple random walks and their first passage times to simulate fluctuations in neuronal membrane potentials and interspike times is also considered.

We studied mechanisms for cortical gamma-band activity in the cerebral cortex and identified neurobiological factors that affect such activity. This was done by analyzing the behavior of a previously developed, data-driven, large-scale network model that simulated many visual functions of monkey V1 cortex (Chariker et al., 2016). Gamma activity was an emergent property of the model. The model's gamma activity, like that of the real cortex, was (1) episodic, (2) variable in frequency and phase, and (3) graded in power with stimulus variables like orientation. The spike firing of the model's neuronal population was only partially synchronous during multiple firing events (MFEs) that occurred at gamma rates. Detailed analysis of the model's MFEs showed that gamma-band activity was multidimensional in its sources. Most spikes were evoked by excitatory inputs. A large fraction of these inputs came from recurrent excitation within the local circuit, but feedforward and feedback excitation also contributed, either through direct pulsing or by raising the overall baseline. Inhibition was responsible for ending MFEs, but disinhibition led directly to only a small minority of the synchronized spikes. As a potential explanation for the wide range of gamma characteristics observed in different parts of cortex, we found that the relative rise times of AMPA and GABA synaptic conductances have a strong effect on the degree of synchrony in gamma. SIGNIFICANCE STATEMENT Canonical computations used throughout the cerebral cortex are performed in primary visual cortex (V1). Providing theoretical mechanisms for these computations will advance understanding of computation throughout cortex. We studied one dynamical feature, gamma-band rhythms, in a large-scale, data-driven, computational model of monkey V1. Our most significant conclusion is that the sources of gamma band activity are multidimensional. A second major finding is that the relative rise times of excitatory and inhibitory synaptic potentials have strong effects on spike synchrony and peak gamma band power. Insight gained from studying our V1 model can shed light on the functions of other cortical regions., (Copyright © 2018 the authors 0270-6474/18/388621-14$15.00/0.)

This numerical study documents and analyzes emergent spiking behavior in local neuronal populations. Emphasis is given to a phenomenon we call clustering, by which we refer to a tendency of random groups of neurons large and small to spontaneously coordinate their spiking activity in some fashion. Using a sparsely connected network of integrate-and-fire neurons, we demonstrate that spike clustering occurs ubiquitously in both high firing and low firing regimes. As a practical tool for quantifying such spike patterns, we propose a simple scheme with two parameters, one setting the temporal scale and the other the amount of deviation from the mean to be regarded as significant. Viewing population activity as a sequence of events, meaning relatively brief durations of elevated spiking, separated by inter-event times, we observe that background activity tends to give rise to extremely broad distributions of event sizes and inter-event times, while driving a system imposes a certain regularity on its inter-event times, producing a rhythm consistent with broad-band gamma oscillations. We note also that event sizes and inter-event times decorrelate very quickly. Dynamical analyses supported by numerical evidence are offered.

Randomly connected networks of neurons driven by Poisson inputs are often assumed to produce "homogeneous" dynamics, characterized by largely independent firing and approximable by diffusion processes. At the same time, it is well known that such networks can fire synchronously. Between these two much studied scenarios lies a vastly complex dynamical landscape that is relatively unexplored. In this paper, we discuss a phenomenon which commonly manifests in these intermediate regimes, namely brief spurts of spiking activity which we call multiple firing events (MFE). These events do not depend on structured network architecture nor on structured input; they are an emergent property of the system. We came upon them in an earlier modeling paper, in which we discovered, through a careful benchmarking process, that MFEs are the single most important dynamical mechanism behind many of the V1 phenomena we were able to replicate. In this paper we explain in a simpler setting how MFEs come about, as well as their potential dynamic consequences. Although the mechanism underlying MFEs cannot easily be captured by current population dynamics models, this phenomena should not be ignored during analysis; there is a growing body of evidence that such collaborative activity may be a key towards unlocking the possible functional properties of many neuronal networks.

We study the reliability of layered networks of coupled "type I" neural oscillators in response to fluctuating input signals. Reliability means that a signal elicits essentially identical responses upon repeated presentations, regardless of the network's initial condition. We study reliability on two distinct scales: neuronal reliability, which concerns the repeatability of spike times of individual neurons embedded within a network, and pooled-response reliability, which concerns the repeatability of total synaptic outputs from a subpopulation of the neurons in a network. We find that neuronal reliability depends strongly both on the overall architecture of a network, such as whether it is arranged into one or two layers, and on the strengths of the synaptic connections. Specifically, for the type of single-neuron dynamics and coupling considered, single-layer networks are found to be very reliable, while two-layer networks lose their reliability with the introduction of even a small amount of feedback. As expected, pooled responses for large enough populations become more reliable, even when individual neurons are not. We also study the effects of noise on reliability, and find that noise that affects all neurons similarly has much greater impact on reliability than noise that affects each neuron differently. Qualitative explanations are proposed for the phenomena observed.

Neuroscience models come in a wide range of scales and specificity, from mean-field rate models to large-scale networks of spiking neurons. There are potential trade-offs between simplicity and realism, versatility and computational speed. This paper is about large-scale cortical network models, and the question we address is one of scalability: would scaling down cell density impact a network’s ability to reproduce cortical dynamics and function? We investigated this problem using a previously constructed realistic model of the monkey visual cortex that is true to size. Reducing cell density gradually up to 50-fold, we studied changes in model behavior. Size reduction without parameter adjustment was catastrophic. Surprisingly, relatively minor compensation in synaptic weights guided by a theoretical algorithm restored mean firing rates and basic function such as orientation selectivity to models 10-20 times smaller than the real cortex. Not all was normal in the reduced model cortices: intracellular dynamics acquired a character different from that of real neurons, and while the ability to relay feedforward inputs remained intact, reduced models showed signs of deficiency in functions that required dynamical interaction among cortical neurons. These findings are not confined to models of the visual cortex, and modelers should be aware of potential issues that accompany size reduction. Broader implications of this study include the importance of homeostatic maintenance of firing rates, and the functional consequences of feedforward versus recurrent dynamics, ideas that may shed light on other species and on systems suffering cell loss. [ABSTRACT FROM AUTHOR]

Perturbation theory is an important tool in the analysis of oscillators and their response to external stimuli. It is predicated on the assumption that the perturbations in question are 'sufficiently weak', an assumption that is not always valid when perturbative methods are applied. In this paper, we identify a number of concrete dynamical scenarios in which a standard perturbative technique, based on the infinitesimal phase response curve (PRC), is shown to give different predictions than the full model. Shear-induced chaos, i.e., chaotic behavior that results from the amplification of small perturbations by underlying shear, is missed entirely by the PRC. We show also that the presence of 'sticky' phase-space structures tend to cause perturbative techniques to overestimate the frequencies and regularity of the oscillations. The phenomena we describe can all be observed in a simple 2D neuron model, which we choose for illustration as the PRC is widely used in mathematical neuroscience. [ABSTRACT FROM AUTHOR]