Publications
- Tibor Rózsa, J. A., Rémy Cagnol. (2024). Iso-orientation bias of layer 2/3 connections: the unifying mechanism of spontaneous, visually and optogenetically driven V1 dynamics. https://doi.org/doi.org/10.1101/2024.11.19.624284
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Functionally specific long-range lateral connectivity in layer 2/3 of the primary visual cortex (V1) supports the integration of visual information across visual space and shapes spontaneous, visual and optogenetically driven V1 activity. However, a comprehensive understanding of how these diverse cortical regimes emerge from this underlying cortical circuitry remains elusive. Here we address this gap by showing how the same model assuming moderately iso-orientation biassed long-range cortical connectivity architecture explains diverse phenomena, including (i) range of visually driven phenomena, (ii) modular spontaneous activity, (iii) the propagation of spontaneous cortical waves, and (iv) neural responses to patterned optogenetic stimulation. The model offers testable predictions, including presence of slower and iso-tropic spontaneous wave propagation in layer 4 and non-monotonicity of optogenetically driven cortical response to increasingly larger disk of illumination. We thus offer a holistic framework for studying how cortical circuitry governs information integration across multiple operating regimes.
- Berling, D., Baroni, L., Chaffiol, A., Gauvain, G., Picaud, S., & Antolik, J. (2024). Consequences of neuronal morphology for spatially precise optogenetic stimulation. https://doi.org/10.1101/2024.03.18.585466 → bibtex
- Antolík, J., Cagnol, R., Rózsa, T., Monier, C., Frégnac, Y., & Davison, A. P. (2024). A comprehensive data-driven model of cat primary visual cortex. PLOS Computational Biology, 20, 1–42.
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Knowledge integration based on the relationship between structure and function of the neural substrate is one of the main targets of neuroinformatics and data-driven computational modeling. However, the multiplicity of data sources, the diversity of benchmarks, the mixing of observables of different natures, and the necessity of a long-term, systematic approach make such a task challenging. Here we present a first snapshot of a long-term integrative modeling program designed to address this issue in the domain of the visual system: a comprehensive spiking model of cat primary visual cortex. The presented model satisfies an extensive range of anatomical, statistical and functional constraints under a wide range of visual input statistics. In the presence of physiological levels of tonic stochastic bombardment by spontaneous thalamic activity, the modeled cortical reverberations self-generate a sparse asynchronous ongoing activity that quantitatively matches a range of experimentally measured statistics. When integrating feed-forward drive elicited by a high diversity of visual contexts, the simulated network produces a realistic, quantitatively accurate interplay between visually evoked excitatory and inhibitory conductances; contrast-invariant orientation-tuning width; center surround interactions; and stimulus-dependent changes in the precision of the neural code. This integrative model offers insights into how the studied properties interact, contributing to a better understanding of visual cortical dynamics. It provides a basis for future development towards a comprehensive model of low-level perception.
- Baroni, L., Bashiri, M., Willeke, K. F., Antolı́k Ján, & Sinz, F. H. (2023). Learning invariance manifolds of visual sensory neurons. NeurIPS Workshop on Symmetry and Geometry in Neural Representations, 301–326. PMLR. → bibtex
- Taylor, M. M., Contreras, D., Destexhe, A., Frégnac, Y., & Antolik, J. (2021). An anatomically constrained model of V1 simple cells predicts the coexistence of push-pull and broad inhibition. Journal of Neuroscience. https://doi.org/10.1523/JNEUROSCI.0928-20.2021
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The spatial organization and dynamic interactions between excitatory and inhibitory synaptic inputs that define the receptive field (RF) of simple cells in cat primary visual cortex (V1) still raise paradoxical issues: 1) stimulation of simple cells in V1 with drifting gratings supports a wiring schema of spatially segregated sets of excitatory and inhibitory inputs activated in an opponent way by stimulus contrast polarity; 2) in contrast, intracellular studies using flashed bars suggest that, while ON and OFF excitatory input are indeed segregated, inhibitory inputs span the entire RF irrespective of input contrast polarity. Here, we propose a biologically detailed computational model of simple cells embedded in a V1-like network that resolves this seeming contradiction. We varied parametrically the RF-correlation-based bias for excitatory and inhibitory synapses and found that a moderate bias of excitatory neurons to synapse onto other neurons with correlated receptive fields, and a weaker bias of inhibitory neurons to synapse onto other neurons with anti-correlated receptive fields can explain the conductance input, the postsynaptic membrane potential, and the spike train dynamics under both stimulation paradigms. This computational study shows that the same structural model can reproduce the functional diversity of visual processing observed during different visual contexts.Significance StatementIdentifying generic connectivity motives in cortical circuitry encoding for specific functions is crucial for understanding the computations implemented in cortex. Indirect evidence points to correlation-based biases in connectivity pattern in V1 of higher mammals, whereby excitatory and inhibitory neurons preferentially synapse onto neurons respectively with correlated and anti-correlated receptive fields. A recent intracellular study questions this “push-pull” hypothesis, failing to find spatial anti-correlation patterns between excitation and inhibition across the receptive field. We present here a spiking model of V1 that integrates relevant anatomical and physiological constraints, and shows that a more versatile motif of correlation-based connectivity with selectively tuned excitation and broadened inhibition is sufficient to account for the diversity of functional descriptions obtained for different classes of stimuli.
- Antolik, J., Sabatier, Q., Galle, C., Frégnac, Y., & Benosman, R. (2021). Assessment of optogenetically-driven strategies for prosthetic restoration of cortical vision in large-scale neural simulation of V1. Scientific Reports, 11, 10783.
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The neural encoding of visual features in primary visual cortex (V1) is well understood, with strong correlates to low-level perception, making V1 a strong candidate for vision restoration through neuroprosthetics. However, the functional relevance of neural dynamics evoked through external stimulation directly imposed at the cortical level is poorly understood. Furthermore, protocols for designing cortical stimulation patterns that would induce a naturalistic perception of the encoded stimuli have not yet been established. Here, we demonstrate a proof of concept by solving these issues through a computational model, combining (1) a large-scale spiking neural network model of cat V1 and (2) a virtual prosthetic system transcoding the visual input into tailored light-stimulation patterns which drive in situ the optogenetically modified cortical tissue. Using such virtual experiments, we design a protocol for translating simple Fourier contrasted stimuli (gratings) into activation patterns of the optogenetic matrix stimulator. We then quantify the relationship between spatial configuration of the imposed light pattern and the induced cortical activity. Our simulations in the absence of visual drive (simulated blindness) show that optogenetic stimulation with a spatial resolution as low as 100
$\upmu 10^16 ^2$ - Antolík, J., & Davison, A. P. (2018). Arkheia: Data Management and Communication for Open Computational Neuroscience. Frontiers in Neuroinformatics, 12, 6.
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Two trends have been unfolding in computational neuroscience during the last decade. First, a shift of focus to increasingly complex and heterogeneous neural network models, with a concomitant increase in the level of collaboration within the field (whether direct or in the form of building on top of existing tools and results). Second, a general trend in science towards more open communication, both internally, with other potential scientific collaborators, and externally, with the wider public. This multi-faceted development towards more integrative approaches and more intense communication within and outside of the field poses major new challenges for modellers, as currently there is a severe lack of tools to help with automatic communication and sharing of all aspects of a simulation workflow to the rest of the community. To address this important gap in the current computational modeling software infrastructure, here we introduce Arkheia. Arkheia is a web-based open science platform for computational models in systems neuroscience. It provides an automatic, interactive, graphical presentation of simulation results, experimental protocols, and interactive exploration of parameter searches, in a web browser-based application. Arkheia is focused on automatic presentation of these resources with minimal manual input from users. Arkheia is written in a modular fashion with a focus on future development of the platform. The platform is designed in an open manner, with a clearly defined and separated API for database access, so that any project can write its own backend translating its data into the Arkheia database format. Arkheia is not a centralized platform, but allows any user (or group of users) to set up their own repository, either for public access by the general population, or locally for internal use. Overall, Arkheia provides users with an automatic means to communicate information about not only their models but also individual simulation results and the entire experimental context in an approachable graphical manner, thus facilitating the user’s ability to collaborate in the field and outreach to a wider audience.
- Antolík, J. (2017). Rapid long-range disynaptic inhibition explains the formation of cortical orientation maps. Frontiers in Neural Circuits, 11, 21.
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Competitive interactions are believed to underlie variety of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g. development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e. excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e. the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neuron). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions in cortex that underlie development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added.
- Antolík, J., Hofer, S. B., Bednar, J. A., & Mrsic-Flogel, T. D. (2016). Model Constrained by Visual Hierarchy Improves Prediction of Neural Responses to Natural Scenes. PLoS Computational Biology, 12, 1–22.
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Accurate estimation of neuronal receptive fields is essential for understanding sensory processing in the early visual system. Yet a full characterization of receptive fields is still incomplete, especially with regard to natural visual stimuli and in complete populations of cortical neurons. While previous work has incorporated known structural properties of the early visual system. such as lateral connectivity, or imposing simple-cell-like receptive field stricure, no study has exploited the fact that nearby V1 neurons share common feed-forward input from thalamus and other upstream cortical neurons. We introduce a new method for estimating receptive fields simultaneously for a population of V1 neurons, using a model-based analysis incorporating knowledge of the feed-forward visual hierarchy. We assume that a population of V1 neurons shares a common pool of thalamic inputs, and consists of two layers of simple and complex-like V1 neurons. When fit to recordings of a local population of mous layer 2/3 V1 neurons, our model offers an accurate description of their response to natural images and significant improvement of prediction power over the current state-of-the-art methods. We shoe that the responses of a large local population of V1 neurons with locally diverse receptive fields can be described with surprisingly limited number of thalamic inputs, consistent with recent experimental findings. Our structural model not only offers an improved functional characterization of V1 neurons, but also provides a framework for studying the relationship between connectivity and function in visual cortical areas.
- Antolík, J., & Davison, A. P. (2013). Integrated workflows for spiking neuronal network simulations. Frontiers in Neuroinformatics, 7, 1–15. → pdf, bibtex
- Ko, H., Cossell, L., Baragli, C., Antolík, J., Clopath, C., Hofer, S. B., & Mrsic-Flogel, T. D. (2013). The emergence of functional microcircuits in visual cortex. Nature, 496, 96–100.
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Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured and excitatory neurons form subnetworks that process related sensory information. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience–a process that may be facilitated by early electrical coupling between neuronal subsets–and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.
- Stevens, J.-L. R., Law, J. S., Antolík, J., & Bednar, J. A. (2013). Mechanisms for stable, robust, and adaptive development of orientation maps in the primary visual cortex. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 33, 15747–15766.
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Development of orientation maps in ferret and cat primary visual cortex (V1) has been shown to be stable, in that the earliest measurable maps are similar in form to the eventual adult map, robust, in that similar maps develop in both dark rearing and in a variety of normal visual environments, and yet adaptive, in that the final map pattern reflects the statistics of the specific visual environment. How can these three properties be reconciled? Using mechanistic models of the development of neural connectivity in V1, we show for the first time that realistic stable, robust, and adaptive map development can be achieved by including two low-level mechanisms originally motivated from single-neuron results. Specifically, contrast-gain control in the retinal ganglion cells and the lateral geniculate nucleus reduces variation in the presynaptic drive due to differences in input patterns, while homeostatic plasticity of V1 neuron excitability reduces the postsynaptic variability in firing rates. Together these two mechanisms, thought to be applicable across sensory systems in general, lead to biological maps that develop stably and robustly, yet adapt to the visual environment. The modeling results suggest that topographic map stability is a natural outcome of low-level processes of adaptation and normalization. The resulting model is more realistic, simpler, and far more robust, and is thus a good starting point for future studies of cortical map development.
- Antolík, J., & Bednar, J. A. (2011). Development of maps of simple and complex cells in the primary visual cortex. Frontiers in Computational Neuroscience, 5, 1–19.
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Hubel & Wiesel classified primary visual cortex (V1) neurons as either simple, with responses modulated by the spatial phase of a sine grating, or complex, i.e. largely phase invariant. Much progress has been made in understanding how simple cells develop, and there are now detailed computational models establishing how they can form topographic maps ordered by orientation preference. There are also models of how complex cells can develop using outputs from simple cells with different phase preferences, but no model of how a topographic orientation map of complex cells could be formed based on the actual connectivity patterns found in V1. Addressing this question is important, because the majority of existing developmental models of simple-cell maps group neurons selective to similar spatial phases together, which is contrary to experimental evidence, and makes it difficult to construct complex cells. Overcoming this limitation is not trivial, because mechanisms responsible for map development drive receptive fields of nearby neurons to be highly correlated, while co-oriented receptive fields of opposite phases are anti-correlated. In this work, we model V1 as two topographically organised sheets representing cortical layer 4 and 2/3. Only layer 4 receives direct thalamic input. Both sheets are connected with narrow feed-forward and feedback connectivity. Only layer 2/3 contains strong long-range lateral connectivity, in line with current anatomical findings. Initially all weights in the model are random, and each is modified via a Hebbian learning rule. The model develops smooth, matching, orientation preference maps in both sheets. Layer 4 units become simple cells, with phase preference arranged randomly, while those in layer 2/3 are primarily complex cells. To our knowledge this model is the first explaining how simple cells can develop with random phase preference, and how maps of complex cells can develop, using only realistic patterns of connectivity.
- Antolík, J. (2005). Automatic annotation of medical records. Studies in Health Technology and Informatics, 116, 817–822.
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One of the research projects running at the medical informatics department of the Institute of Computer Science AS CR explores the problem of medical information representation and development of electronic health record (EHR). With respect to this effort an interesting problem arises: how to transfer knowledge from a medical record written in a free text form into a structured electronic format represented by the EHR. Currently, this task was solved by writing extraction rules (regular expressions) for every element of information that is to be extracted from the medical record. However, such approach is very time consuming and requires supervision of a skilled programmer whenever the target area of medicine is changed. In this article we explore the possibility to mechanize this process by automatically generating the extraction rules from a pre-annotated corpus of medical records. Since we are currently in the phase of data acquisition and preliminary tests we will not present any final results, rather we will sketch the technologies we intend to use and describe the tools that were developed so far as a part of this project.
- Antolík, J., & Hsu, W. H. (2005). Evolutionary tree genetic programming. Proceedings of the 2005 Conference on Genetic and Evolutionary Computation - GECCO ’05, 1789. → pdf, bibtex