Neuronal Circuit Model Research Articles

Modulation of SK Channels via Calcium Buffering Tunes Intrinsic Excitability of Parvalbumin Interneurons in Neuropathic Pain: A Computational and Experimental Investigation.

Parvalbumin-expressing interneurons (PVINs) play a crucial role within the dorsal horn of the spinal cord by preventing touch inputs from activating pain circuits. In both male and female mice, nerve injury decreases PVINs' output via mechanisms that are not fully understood. In this study, we show that PVINs from nerve-injured male mice change their firing pattern from tonic to adaptive. To examine the ionic mechanisms responsible for this decreased output, we used a reparametrized Hodgkin-Huxley type model of PVINs, which predicted (1) the firing pattern transition is because of an increased contribution of small conductance calcium-activated potassium (SK) channels, enabled by (2) impairment in intracellular calcium buffering systems. Analyzing the dynamics of the Hodgkin-Huxley type model further demonstrated that a generalized Hopf bifurcation differentiates the two types of state transitions observed in the transient firing of PVINs. Importantly, this predicted mechanism holds true when we embed the PVIN model within the neuronal circuit model of the spinal dorsal horn. To experimentally validate this hypothesized mechanism, we used pharmacological modulators of SK channels and demonstrated that (1) tonic firing PVINs from naive male mice become adaptive when exposed to an SK channel activator, and (2) adapting PVINs from nerve-injured male mice return to tonic firing on SK channel blockade. Our work provides important insights into the cellular mechanism underlying the decreased output of PVINs in the spinal dorsal horn after nerve injury and highlights potential pharmacological targets for new and effective treatment approaches to neuropathic pain.SIGNIFICANCE STATEMENT Parvalbumin-expressing interneurons (PVINs) exert crucial inhibitory control over Aβ fiber-mediated nociceptive pathways at the spinal dorsal horn. The loss of their inhibitory tone leads to neuropathic symptoms, such as mechanical allodynia, via mechanisms that are not fully understood. This study identifies the reduced intrinsic excitability of PVINs as a potential cause for their decreased inhibitory output in nerve-injured condition. Combining computational and experimental approaches, we predict a calcium-dependent mechanism that modulates PVINs' electrical activity following nerve injury: a depletion of cytosolic calcium buffer allows for the rapid accumulation of intracellular calcium through the active membranes, which in turn potentiates SK channels and impedes spike generation. Our results therefore pinpoint SK channels as potential therapeutic targets for treating neuropathic symptoms.

Memristive biophysical neuron models forming an excitatory–inhibitory neural network for modeling PING rhythm generation

SPICE models are constructed for memristive devices to form associated biophysical neuron circuit models such as the Hodgkin–Huxley (HH) type II excitability neuron circuit model, the HH type III excitability neuron circuit model, the simplified HH neuron circuit model, the Morris–Lecar neuron circuit model, and the memristive based direct-current (DC) circuit model. Rigorous nonlinear circuit-theoretic principles are also applied to analyze the different behaviors of the generic memristor Na $$^{+}$$ -ion, K $$^{+}$$ -ion, and Ca $$^{++}$$ -ion channels forming these biophysical neuron circuit models. Detailed explanations and clarifications are presented on the memristive HH type II and HH type III axonal excitabilities based on mathematical analysis as well as the circuit models. This is done from the perspective of the spike patterns generated by both of these biophysical neuron circuit models. Moreover, various experimental studies have revealed a synchronous brain state known as gamma rhythms that are responsible for sensory, memory, and motor processes. This suggests that understanding how the gamma oscillation (30–100 Hz) is generated in the brain will be extremely important to unravel the link between the activity of an individual neuron and the cognitive processing achieved by a population of networked neurons. We thus also study the dynamics of an interconnected excitatory–inhibitory (E–I) network population, which is ubiquitous in the brain. Utilizing biophysical models of the E–I network, we investigate the generation of pyramidal-interneuronal network gamma (PING) rhythms caused by the external input to the network and the connectivity heterogeneities. The results reveal that synchronous strong PING and sparsely firing weak PING rhythms are generated based on the network connectivities and external input heterogeneities in simulations of 100 memristive HH type II excitability neurons forming an E–I network.

Simultaneous monitoring of action potentials and neurotransmitter release from neuron-like PC12 cells

Simultaneous recording of action potentials (APs) and neurotransmitter release is highly desirable in living neurons since it provides a complete framework of the physiological and pathological statuses of nerve cells. In this work, we proposed an approach coupling ultra-thin microelectrode array (MEA) with total internal reflection fluorescence microscopy (TIRFM), which served as a powerful platform to visualize both APs and vesicular exocytosis in a neuronal circuit model formed by neuron-like PC12cells. Taking advantages of fluorescent false neurotransmitter (FFN), the transient neurotransmitter transport down an axon could be visualized with high spatial and temporal resolution. The real-time recording of APs burst and neurotransmitter release induced by hypoxia with MEA/TIRFM platform reveals the relevance of electrical and chemical activities in the neuronal model. The combination of the optical and electrical techniques enables mapping of neuron connectivity in an entire neuronal circuit, which may ultimately lead to deeper understanding of nervous system.

Hybrid neuromorphic circuits exploiting non-conventional properties of RRAM for massively parallel local plasticity mechanisms

Recurrent neural networks are currently subject to intensive research efforts to solve temporal computing problems. Neuromorphic processors (NPs), composed of networked neuron and synapse circuit models, natively compute in time and offer an ultralow power solution particularly suited to emerging temporal edge-computing applications (wearable medical devices, for example). The most significant roadblock to addressing useful problems with neuromorphic hardware is the difficulty in maintaining healthy network dynamics in recurrent neural networks. In animal nervous systems, this is achieved via a multitude of adaptive homeostatic mechanisms which act over multiple time scales to counteract network instability induced via drift, component failure, or learning processes such as spike-timing dependent plasticity. One such mechanism is neuronal intrinsic plasticity (IP) where a neuron adapts its parameters which govern its excitability to fire around a target rate. The approach employed in state of the art NPs, based on a central volatile memory remotely setting model parameters, critically constrains parameter variety and bandwidth rendering realization of these essential mechanisms impossible. This paper demonstrates how reconfigurable nonvolatile resistive memories can be incorporated into neuron and synapse circuits allowing memory to be truly colocalized with the computational units in the computing fabric and facilitating the realization of massively parallel local plasticity mechanisms in neuromorphic hardware. Exploiting nonconventional programming operations of HfO2 based RRAM (stochastic SET and the RESET random variable), we propose a technologically plausible IP algorithm and demonstrate its use in the case of a recurrent neural network topology whereby the system self-organizes to sustain stable and healthy network dynamics around a target firing rate.

A neural circuit model of decision uncertainty and change-of-mind

Decision-making is often accompanied by a degree of confidence on whether a choice is correct. Decision uncertainty, or lack in confidence, may lead to change-of-mind. Studies have identified the behavioural characteristics associated with decision confidence or change-of-mind, and their neural correlates. Although several theoretical accounts have been proposed, there is no neural model that can compute decision uncertainty and explain its effects on change-of-mind. We propose a neuronal circuit model that computes decision uncertainty while accounting for a variety of behavioural and neural data of decision confidence and change-of-mind, including testable model predictions. Our theoretical analysis suggests that change-of-mind occurs due to the presence of a transient uncertainty-induced choice-neutral stable steady state and noisy fluctuation within the neuronal network. Our distributed network model indicates that the neural basis of change-of-mind is more distinctively identified in motor-based neurons. Overall, our model provides a framework that unifies decision confidence and change-of-mind.

Theoretical optimization of high-frequency optogenetic spiking of red-shifted very fast-Chrimson-expressing neurons.

A detailed theoretical analysis and optimization of high-fidelity, high-frequency firing of the red-shifted very-fast-Chrimson (vf-Chrimson) expressing neurons is presented. A four-state model for vf-Chrimson photocycle has been formulated and incorporated in Hodgkin-Huxley and Wang-Buzsaki spiking neuron circuit models. The effect of various parameters that include irradiance, pulse width, frequency, expression level, and membrane capacitance has been studied in detail. Theoretical simulations are in excellent agreement with recently reported experimental results. The analysis and optimization bring out additional interesting features. A minimal pulse width of 1.7ms at induces a peak photocurrent of 1250pA. Optimal irradiance ( ) and pulse width ( ) to trigger action potential have been determined. At frequencies beyond 200Hz, higher values of expression level and irradiance result in spike failure. Singlet and doublet spiking fidelity can be maintained up to 400 and 150Hz, respectively. The combination of expression level and membrane capacitance is a crucial factor to achieve high-frequency firing above 500Hz. Its optimization enables 100% spike probability of up to 1kHz. The study is useful in designing new high-frequency optogenetic neural spiking experiments with desired spatiotemporal resolution, by providing insights into the temporal spike coding, plasticity, and curing neurodegenerative diseases.

Towards systematic, data-driven validation of a collaborative, multi-scale model of Caenorhabditis elegans.

The OpenWorm Project is an international open-source collaboration to create a multi-scale model of the organism Caenorhabditis elegans At each scale, including subcellular, cellular, network and behaviour, this project employs one or more computational models that aim to recapitulate the corresponding biological system at that scale. This requires that the simulated behaviour of each model be compared with experimental data both as the model is continuously refined and as new experimental data become available. Here we report the use of SciUnit, a software framework for model validation, to attempt to achieve these goals. During project development, each model is continuously subjected to data-driven 'unit tests' that quantitatively summarize model-data agreement, identifying modelling progress and highlighting particular aspects of each model that fail to adequately reproduce known features of the biological organism and its components. This workflow is publicly visible via both GitHub and a web application and accepts community contributions to ensure that modelling goals are transparent and well-informed.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.

NeuroMorphoVis: a collaborative framework for analysis and visualization of neuronal morphology skeletons reconstructed from microscopy stacks.

MotivationFrom image stacks to computational models, processing digital representations of neuronal morphologies is essential to neuroscientific research. Workflows involve various techniques and tools, leading in certain cases to convoluted and fragmented pipelines. The existence of an integrated, extensible and free framework for processing, analysis and visualization of those morphologies is a challenge that is still largely unfulfilled.ResultsWe present NeuroMorphoVis, an interactive, extensible and cross-platform framework for building, visualizing and analyzing digital reconstructions of neuronal morphology skeletons extracted from microscopy stacks. Our framework is capable of detecting and repairing tracing artifacts, allowing the generation of high fidelity surface meshes and high resolution volumetric models for simulation and in silico imaging studies. The applicability of NeuroMorphoVis is demonstrated with two case studies. The first simulates the construction of three-dimensional profiles of neuronal somata and the other highlights how the framework is leveraged to create volumetric models of neuronal circuits for simulating different types of in vitro imaging experiments.Availability and implementationThe source code and documentation are freely available on https://github.com/BlueBrain/NeuroMorphoVis under the GNU public license. The morphological analysis, visualization and surface meshing are implemented as an extensible Python API (Application Programming Interface) based on Blender, and the volume reconstruction and analysis code is written in C++ and parallelized using OpenMP. The framework features are accessible from a user-friendly GUI (Graphical User Interface) and a rich CLI (Command Line Interface).Supplementary information Supplementary data are available at Bioinformatics online.

A Scalable Weight-Free Learning Algorithm for Regulatory Control of Cell Activity in Spiking Neuronal Networks.

Recent developments in neural stimulation and recording technologies are providing scientists with the ability of recording and controlling the activity of individual neurons in vitro or in vivo, with very high spatial and temporal resolution. Tools such as optogenetics, for example, are having a significant impact in the neuroscience field by delivering optical firing control with the precision and spatiotemporal resolution required for investigating information processing and plasticity in biological brains. While a number of training algorithms have been developed to date for spiking neural network (SNN) models of biological neuronal circuits, exiting methods rely on learning rules that adjust the synaptic strengths (or weights) directly, in order to obtain the desired network-level (or functional-level) performance. As such, they are not applicable to modifying plasticity in biological neuronal circuits, in which synaptic strengths only change as a result of pre- and post-synaptic neuron firings or biological mechanisms beyond our control. This paper presents a weight-free training algorithm that relies solely on adjusting the spatiotemporal delivery of neuron firings in order to optimize the network performance. The proposed weight-free algorithm does not require any knowledge of the SNN model or its plasticity mechanisms. As a result, this training approach is potentially realizable in vitro or in vivo via neural stimulation and recording technologies, such as optogenetics and multielectrode arrays, and could be utilized to control plasticity at multiple scales of biological neuronal circuits. The approach is demonstrated by training SNNs with hundreds of units to control a virtual insect navigating in an unknown environment.

Ergodicity and parameter estimates in auditory neural circuits

This paper discusses ergodic properties and circular statistical characteristics in neuronal spike trains. Ergodicity means that the average taken over a long time period and over smaller population should equal the average in less time and larger population. The objectives are to show simple examples of design and validation of a neuronal model, where the ergodicity assumption helps find correspondence between variables and parameters. The methods used are analytical and numerical computations, numerical models of phenomenological spiking neurons and neuronal circuits. Results obtained using these methods are the following. They are: a formula to calculate vector strength of neural spike timing dependent on the spike train parameters, description of parameters of spike train variability and model of output spiking density based on assumption of the computation realized by sound localization neural circuit. Theoretical results are illustrated by references to experimental data. Examples of neurons where spike trains have and do not have the ergodic property are then discussed.

A Framework for Collaborative Curation of Neuroscientific Literature.

Large models of complex neuronal circuits require specifying numerous parameters, with values that often need to be extracted from the literature, a tedious and error-prone process. To help establishing shareable curated corpora of annotations, we have developed a literature curation framework comprising an annotation format, a Python API (NeuroAnnotation Toolbox; NAT), and a user-friendly graphical interface (NeuroCurator). This framework allows the systematic annotation of relevant statements and model parameters. The context of the annotated content is made explicit in a standard way by associating it with ontological terms (e.g., species, cell types, brain regions). The exact position of the annotated content within a document is specified by the starting character of the annotated text, or the number of the figure, the equation, or the table, depending on the context. Alternatively, the provenance of parameters can also be specified by bounding boxes. Parameter types are linked to curated experimental values so that they can be systematically integrated into models. We demonstrate the use of this approach by releasing a corpus describing different modeling parameters associated with thalamo-cortical circuitry. The proposed framework supports a rigorous management of large sets of parameters, solving common difficulties in their traceability. Further, it allows easier classification of literature information and more efficient and systematic integration of such information into models and analyses.

Dejerines’ findings about alexia and their meaning for the Japanese language

Dejerine's Discovery of the role of the left angular gyrus as the center of reading and writing in 1891 and in 1892 was the beginning of a new field of neuroscience, which I called “Neurogrammatology.” His diagram of neuronal circuit of reading and writing was later revised by Geschwind in 1965 and has been widely accepted. Japanese neuropsychologists, however, have since long been puzzled about the problem of alexia and agraphia of “kanji” which can hardly be explained by Dejerine's diagram. Japanese language has two different types of letters; “kana” (phonogram) and “kanji” (morphogram). The reading and writing disturbances of “kana” in focal brain damage can be very well explained by Dejerine's diagram, but as to “kanji”, the left medial occipital lesion which usually causes alexia without agraphia in western language cause alexia with agraphia of “kanji”. On the other hand, a focal lesion of the left angular gyrus causes only agraphia for “kanji”. As the third type of alexia in Japanese language, we have found cases of alexia and agraphia affecting only “kanji” caused by lesions of the posterior-inferior part of left temporal lobe. Basing upon these clinical observations, we proposed a dual neuronal circuit model of reading and writing in Japanese language [1] . Then we did PET scan activation studies on the normal subjects and found the two cortical areas of the left cerebral hemisphere which are indispensable for reading: area 37 responsible for semantic reading and area 19 just behind the angular gyrus for phonological reading. The phonological reading circuit is the main stream of reading “kana” and the semantic circuit is requisite for reading “kanji” [2] . As a result, we proposed a new diagram of dual neuronal circuits of reading process of Japanese language as shown in Fig. 1 [3] .

Synchrony dynamics underlying effective connectivity reconstruction of neuronal circuits

Reconstruction of effective connectivity between neurons is essential for neural systems with function-related significance, characterizing directionally causal influences among neurons. In this work, causal interactions between neurons in spinal dorsal root ganglion, activated by manual acupuncture at Zusanli acupoint of experimental rats, are estimated using Granger causality (GC) method. Different patterns of effective connectivity are obtained for different frequencies and types of acupuncture. Combined with synchrony analysis between neurons, we show a dependence of effective connection on the synchronization dynamics. Based on the experimental findings, a neuronal circuit model with synaptic connections is constructed. The variation of neuronal effective connectivity with respect to its structural connectivity and synchronization dynamics is further explored. Simulation results show that reciprocally causal interactions with statistically significant are formed between well-synchronized neurons. The effective connectivity may be not necessarily equivalent to synaptic connections, but rather depend on the synchrony relationship. Furthermore, transitions of effective interaction between neurons are observed following the synchronization transitions induced by conduction delay and synaptic conductance. These findings are helpful to further investigate the dynamical mechanisms underlying the reconstruction of effective connectivity of neuronal population.

Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscience.

Neuron modeling may be said to have originated with the Hodgkin and Huxley action potential model in 1952 and Rall's models of integrative activity of dendrites in 1964. Over the ensuing decades, these approaches have led to a massive development of increasingly accurate and complex data-based models of neurons and neuronal circuits. ModelDB was founded in 1996 to support this new field and enhance the scientific credibility and utility of computational neuroscience models by providing a convenient venue for sharing them. It has grown to include over 1100 published models covering more than 130 research topics. It is actively curated and developed to help researchers discover and understand models of interest. ModelDB also provides mechanisms to assist running models both locally and remotely, and has a graphical tool that enables users to explore the anatomical and biophysical properties that are represented in a model. Each of its capabilities is undergoing continued refinement and improvement in response to user experience. Large research groups (Allen Brain Institute, EU Human Brain Project, etc.) are emerging that collect data across multiple scales and integrate that data into many complex models, presenting new challenges of scale. We end by predicting a future for neuroscience increasingly fueled by new technology and high performance computation, and increasingly in need of comprehensive user-friendly databases such as ModelDB to provide the means to integrate the data for deeper insights into brain function in health and disease.

Comparing Neuromorphic Solutions in Action: Implementing a Bio-Inspired Solution to a Benchmark Classification Task on Three Parallel-Computing Platforms.

Neuromorphic computing employs models of neuronal circuits to solve computing problems. Neuromorphic hardware systems are now becoming more widely available and “neuromorphic algorithms” are being developed. As they are maturing toward deployment in general research environments, it becomes important to assess and compare them in the context of the applications they are meant to solve. This should encompass not just task performance, but also ease of implementation, speed of processing, scalability, and power efficiency. Here, we report our practical experience of implementing a bio-inspired, spiking network for multivariate classification on three different platforms: the hybrid digital/analog Spikey system, the digital spike-based SpiNNaker system, and GeNN, a meta-compiler for parallel GPU hardware. We assess performance using a standard hand-written digit classification task. We found that whilst a different implementation approach was required for each platform, classification performances remained in line. This suggests that all three implementations were able to exercise the model's ability to solve the task rather than exposing inherent platform limits, although differences emerged when capacity was approached. With respect to execution speed and power consumption, we found that for each platform a large fraction of the computing time was spent outside of the neuromorphic device, on the host machine. Time was spent in a range of combinations of preparing the model, encoding suitable input spiking data, shifting data, and decoding spike-encoded results. This is also where a large proportion of the total power was consumed, most markedly for the SpiNNaker and Spikey systems. We conclude that the simulation efficiency advantage of the assessed specialized hardware systems is easily lost in excessive host-device communication, or non-neuronal parts of the computation. These results emphasize the need to optimize the host-device communication architecture for scalability, maximum throughput, and minimum latency. Moreover, our results indicate that special attention should be paid to minimize host-device communication when designing and implementing networks for efficient neuromorphic computing.

Organization of left-right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling.

Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0D and excitatory V0V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left-right alternation at different locomotor speeds. We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0D , V2a-V0V and V3 neuron populations. The models reproduce the experimentally observed speed-dependent left-right coordination in normal mice and the changes in coordination seen in mutants lacking specific neuron classes. The models propose an explanation for several experimental results and provide insights into the organization of the spinal locomotor network and parallel CIN pathways involved in gait control at different locomotor speeds. Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D ) and excitatory (V0V ) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left-right alternation of neural activity, switching gaits between the left-right alternating walking-like activity and the left-right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits.

The rectification of an electrical synapse can change the functional output of a pattern-generating circuit

Electrical synapses are known to promote synchrony and speed in neuronal systems. However, other studies have found that electrical synapses can have the opposite effect by desynchronizing network neurons. Although they are mechanistically simple, electrical synapses can have unintuitive effects on neuronal network activity. The present study aims to further our understanding of electrical synapses by exploring their rectification in a neuronal circuit model. Rectification is the asymmetrical passage of current through a gap junction between two neurons and it is often likened to a diode in an electrical circuit. Rectifying electrical synapses have been shown to support specialized functions in several biological preparations [1]. We investigate how rectification affects the functional output of a 5-cell, pattern-generating, model network and its sensitivity to synaptic modulation. The circuit is composed of heterogeneous neurons with different intrinsic oscillation frequencies. Neurons were modeled as Morris-Lecar [2] neurons modified by a hyperpolarization-activated current as in a previous study [3]. We find that circuit output depends on the polarity and placement of the rectifying electrical synapse and the intrinsic properties of the neurons on either side of it (Figure 1). Furthermore, using the parameterscape visualization method [3], we find that rectification can affect the circuit’s sensitivity to modulation of synaptic strength including modulation of chemical synapse strength. This

Recurrent Connectivity Can Account for the Dynamics of Disparity Processing in V1

Disparity tuning measured in the primary visual cortex (V1) is described well by the disparity energy model, but not all aspects of disparity tuning are fully explained by the model. Such deviations from the disparity energy model provide us with insight into how network interactions may play a role in disparity processing and help to solve the stereo correspondence problem. Here, we propose a neuronal circuit model with recurrent connections that provides a simple account of the observed deviations. The model is based on recurrent connections inferred from neurophysiological observations on spike timing correlations, and is in good accord with existing data on disparity tuning dynamics. We further performed two additional experiments to test predictions of the model. First, we increased the size of stimuli to drive more neurons and provide a stronger recurrent input. Our model predicted sharper disparity tuning for larger stimuli. Second, we displayed anticorrelated stereograms, where dots of opposite luminance polarity are matched between the left- and right-eye images and result in inverted disparity tuning in the disparity energy model. In this case, our model predicted reduced sharpening and strength of inverted disparity tuning. For both experiments, the dynamics of disparity tuning observed from the neurophysiological recordings in macaque V1 matched model simulation predictions. Overall, the results of this study support the notion that, while the disparity energy model provides a primary account of disparity tuning in V1 neurons, neural disparity processing in V1 neurons is refined by recurrent interactions among elements in the neural circuit.

Integrated workflows for spiking neuronal network simulations

The increasing availability of computational resources is enabling more detailed, realistic modeling in computational neuroscience, resulting in a shift toward more heterogeneous models of neuronal circuits, and employment of complex experimental protocols. This poses a challenge for existing tool chains, as the set of tools involved in a typical modeler's workflow is expanding concomitantly, with growing complexity in the metadata flowing between them. For many parts of the workflow, a range of tools is available; however, numerous areas lack dedicated tools, while integration of existing tools is limited. This forces modelers to either handle the workflow manually, leading to errors, or to write substantial amounts of code to automate parts of the workflow, in both cases reducing their productivity. To address these issues, we have developed Mozaik: a workflow system for spiking neuronal network simulations written in Python. Mozaik integrates model, experiment and stimulation specification, simulation execution, data storage, data analysis and visualization into a single automated workflow, ensuring that all relevant metadata are available to all workflow components. It is based on several existing tools, including PyNN, Neo, and Matplotlib. It offers a declarative way to specify models and recording configurations using hierarchically organized configuration files. Mozaik automatically records all data together with all relevant metadata about the experimental context, allowing automation of the analysis and visualization stages. Mozaik has a modular architecture, and the existing modules are designed to be extensible with minimal programming effort. Mozaik increases the productivity of running virtual experiments on highly structured neuronal networks by automating the entire experimental cycle, while increasing the reliability of modeling studies by relieving the user from manual handling of the flow of metadata between the individual workflow stages.

Competition Through Selective Inhibitory Synchrony

Models of cortical neuronal circuits commonly depend on inhibitory feedback to control gain, provide signal normalization, and selectively amplify signals using winner-take-all (WTA) dynamics. Such models generally assume that excitatory and inhibitory neurons are able to interact easily because their axons and dendrites are colocalized in the same small volume. However, quantitative neuroanatomical studies of the dimensions of axonal and dendritic trees of neurons in the neocortex show that this colocalization assumption is not valid. In this letter, we describe a simple modification to the WTA circuit design that permits the effects of distributed inhibitory neurons to be coupled through synchronization, and so allows a single WTA to be distributed widely in cortical space, well beyond the arborization of any single inhibitory neuron and even across different cortical areas. We prove by nonlinear contraction analysis and demonstrate by simulation that distributed WTA subsystems combined by such inhibitory synchrony are inherently stable. We show analytically that synchronization is substantially faster than winner selection. This circuit mechanism allows networks of independent WTAs to fully or partially compete with other.