The Tripod neuron: a minimal structural reduction of the dendritic tree.

Neuron models with explicit dendritic dynamics have shed light on mechanisms for coincidence detection, pathway selection and temporal filtering. However, it is still unclear which morphological and physiological features are required to capture these phenomena. In this work, we introduce the Tripod neuron model and propose a minimal structural reduction of the dendritic tree that is able to reproduce these computations. The Tripod is a three-compartment model consisting of two segregated passive dendrites and a somatic compartment modelled as an adaptive, exponential integrate-and-fire neuron. It incorporates dendritic geometry, membrane physiology and receptor dynamics as measured in human pyramidal cells. We characterize the response of the Tripod to glutamatergic and GABAergic inputs and identify parameters that support supra-linear integration, coincidence-detection and pathway-specific gating through shunting inhibition. Following NMDA spikes, the Tripod neuron generates plateau potentials whose duration depends on the dendritic length and the strength of synaptic input. When fitted with distal compartments, the Tripod encodes previous activity into a dendritic depolarized state. This dendritic memory allows the neuron to perform temporal binding, and we show that it solves transition and sequence detection tasks on which a single-compartment model fails. Thus, the Tripod can account for dendritic computations previously explained only with more detailed neuron models or neural networks. Due to its simplicity, the Tripod neuron can be used efficiently in simulations of larger cortical circuits. KEY POINTS: We present a neuron model, called the Tripod, with two segregated dendritic branches that are connected to an axosomatic compartment. Each branch implements inhibitory GABAergic and excitatory glutamatergic synaptic transmission, including voltage-gated NMDA receptors. Dendrites are modelled on relevant geometric and physiological parameters measured in human pyramidal cells. The neuron reproduces classical dendritic computations, such as coincidence detection and pathway selection via shunting inhibition, that are beyond the scope of point-neuron models. Under some conditions, dendritic NMDA spikes cause plateau potentials, and we show that they provide a form of short-term memory which is useful for sequence recognition. The dendritic structure of the Tripod neuron is sufficiently simple to be integrated into efficient network simulations and studied in a broad functional context.

Neuronal spike-rate adaptation supports working memory in language processing.

Language processing involves the ability to store and integrate pieces of information in working memory over short periods of time. According to the dominant view, information is maintained through sustained, elevated neural activity. Other work has argued that short-term synaptic facilitation can serve as a substrate of memory. Here we propose an account where memory is supported by intrinsic plasticity that downregulates neuronal firing rates. Single neuron responses are dependent on experience, and we show through simulations that these adaptive changes in excitability provide memory on timescales ranging from milliseconds to seconds. On this account, spiking activity writes information into coupled dynamic variables that control adaptation and move at slower timescales than the membrane potential. From these variables, information is continuously read back into the active membrane state for processing. This neuronal memory mechanism does not rely on persistent activity, excitatory feedback, or synaptic plasticity for storage. Instead, information is maintained in adaptive conductances that reduce firing rates and can be accessed directly without cued retrieval. Memory span is systematically related to both the time constant of adaptation and baseline levels of neuronal excitability. Interference effects within memory arise when adaptation is long lasting. We demonstrate that this mechanism is sensitive to context and serial order which makes it suitable for temporal integration in sequence processing within the language domain. We also show that it enables the binding of linguistic features over time within dynamic memory registers. This work provides a step toward a computational neurobiology of language.

Modeling cancer immunoediting in tumor microenvironment with system characterization through the ising-model Hamiltonian.

BACKGROUND AND OBJECTIVE: Cancer Immunoediting (CI) describes the cellular-level interaction between tumor cells and the Immune System (IS) that takes place in the Tumor Micro-Environment (TME). CI is a highly dynamic and complex process comprising three distinct phases (Elimination, Equilibrium and Escape) wherein the IS can both protect against cancer development as well as, over time, promote the appearance of tumors with reduced immunogenicity. Herein we present an agent-based model for the simulation of CI in the TME, with the objective of promoting the understanding of this process. METHODS: Our model includes agents for tumor cells and for elements of the IS. The actions of these agents are governed by probabilistic rules, and agent recruitment (including cancer growth) is modeled via logistic functions. The system is formalized as an analogue of the Ising model from statistical mechanics to facilitate its analysis. The model was implemented in the Netlogo modeling environment and simulations were performed to verify, illustrate and characterize its operation. RESULTS: A main result from our simulations is the generation of emergent behavior in silico that is very difficult to observe directly in vivo or even in vitro. Our model is capable of generating the three phases of CI; it requires only a couple of control parameters and is robust to these. We demonstrate how our simulated system can be characterized through the Ising-model energy function, or Hamiltonian, which captures the "energy" involved in the interaction between agents and presents it in clear and distinct patterns for the different phases of CI. CONCLUSIONS: The presented model is very flexible and robust, captures well the behaviors of the target system and can be easily extended to incorporate more variables such as those pertaining to different anti-cancer therapies. System characterization via the Ising-model Hamiltonian is a novel and powerful tool for a better understanding of CI and the development of more effective treatments. Since data of CI at the cellular level is very hard to procure, our hope is that tools such as this may be adopted to shed light on CI and related developing theories.

Firing rate homeostasis counteracts changes in stability of recurrent neural networks caused by synapse loss in Alzheimer's disease.

The impairment of cognitive function in Alzheimer's disease is clearly correlated to synapse loss. However, the mechanisms underlying this correlation are only poorly understood. Here, we investigate how the loss of excitatory synapses in sparsely connected random networks of spiking excitatory and inhibitory neurons alters their dynamical characteristics. Beyond the effects on the activity statistics, we find that the loss of excitatory synapses on excitatory neurons reduces the network's sensitivity to small perturbations. This decrease in sensitivity can be considered as an indication of a reduction of computational capacity. A full recovery of the network's dynamical characteristics and sensitivity can be achieved by firing rate homeostasis, here implemented by an up-scaling of the remaining excitatory-excitatory synapses. Mean-field analysis reveals that the stability of the linearised network dynamics is, in good approximation, uniquely determined by the firing rate, and thereby explains why firing rate homeostasis preserves not only the firing rate but also the network's sensitivity to small perturbations.

Leveraging heterogeneity for neural computation with fading memory in layer 2/3 cortical microcircuits.

Complexity and heterogeneity are intrinsic to neurobiological systems, manifest in every process, at every scale, and are inextricably linked to the systems' emergent collective behaviours and function. However, the majority of studies addressing the dynamics and computational properties of biologically inspired cortical microcircuits tend to assume (often for the sake of analytical tractability) a great degree of homogeneity in both neuronal and synaptic/connectivity parameters. While simplification and reductionism are necessary to understand the brain's functional principles, disregarding the existence of the multiple heterogeneities in the cortical composition, which may be at the core of its computational proficiency, will inevitably fail to account for important phenomena and limit the scope and generalizability of cortical models. We address these issues by studying the individual and composite functional roles of heterogeneities in neuronal, synaptic and structural properties in a biophysically plausible layer 2/3 microcircuit model, built and constrained by multiple sources of empirical data. This approach was made possible by the emergence of large-scale, well curated databases, as well as the substantial improvements in experimental methodologies achieved over the last few years. Our results show that variability in single neuron parameters is the dominant source of functional specialization, leading to highly proficient microcircuits with much higher computational power than their homogeneous counterparts. We further show that fully heterogeneous circuits, which are closest to the biophysical reality, owe their response properties to the differential contribution of different sources of heterogeneity.

Toward reproducible models of sequence learning: replication and analysis of a modular spiking network with reward-based learning.

To acquire statistical regularities from the world, the brain must reliably process, and learn from, spatio-temporally structured information. Although an increasing number of computational models have attempted to explain how such sequence learning may be implemented in the neural hardware, many remain limited in functionality or lack biophysical plausibility. If we are to harvest the knowledge within these models and arrive at a deeper mechanistic understanding of sequential processing in cortical circuits, it is critical that the models and their findings are accessible, reproducible, and quantitatively comparable. Here we illustrate the importance of these aspects by providing a thorough investigation of a recently proposed sequence learning model. We re-implement the modular columnar architecture and reward-based learning rule in the open-source NEST simulator, and successfully replicate the main findings of the original study. Building on these, we perform an in-depth analysis of the model's robustness to parameter settings and underlying assumptions, highlighting its strengths and weaknesses. We demonstrate a limitation of the model consisting in the hard-wiring of the sequence order in the connectivity patterns, and suggest possible solutions. Finally, we show that the core functionality of the model is retained under more biologically-plausible constraints.

Signal denoising through topographic modularity of neural circuits.

Information from the sensory periphery is conveyed to the cortex via structured projection pathways that spatially segregate stimulus features, providing a robust and efficient encoding strategy. Beyond sensory encoding, this prominent anatomical feature extends throughout the neocortex. However, the extent to which it influences cortical processing is unclear. In this study, we combine cortical circuit modeling with network theory to demonstrate that the sharpness of topographic projections acts as a bifurcation parameter, controlling the macroscopic dynamics and representational precision across a modular network. By shifting the balance of excitation and inhibition, topographic modularity gradually increases task performance and improves the signal-to-noise ratio across the system. We demonstrate that in biologically constrained networks, such a denoising behavior is contingent on recurrent inhibition. We show that this is a robust and generic structural feature that enables a broad range of behaviorally relevant operating regimes, and provide an in-depth theoretical analysis unraveling the dynamical principles underlying the mechanism.

A refined information processing capacity metric allows an in-depth analysis of memory and nonlinearity trade-offs in neurocomputational systems.

Since dynamical systems are an integral part of many scientific domains and can be inherently computational, analyses that reveal in detail the functions they compute can provide the basis for far-reaching advances in various disciplines. One metric that enables such analysis is the information processing capacity. This method not only provides us with information about the complexity of a system's computations in an interpretable form, but also indicates its different processing modes with different requirements on memory and nonlinearity. In this paper, we provide a guideline for adapting the application of this metric to continuous-time systems in general and spiking neural networks in particular. We investigate ways to operate the networks deterministically to prevent the negative effects of randomness on their capacity. Finally, we present a method to remove the restriction to linearly encoded input signals. This allows the separate analysis of components within complex systems, such as areas within large brain models, without the need to adapt their naturally occurring inputs.

Characteristic columnar connectivity caters to cortical computation: Replication, simulation, and evaluation of a microcircuit model.

The neocortex, and with it the mammalian brain, achieves a level of computational efficiency like no other existing computational engine. A deeper understanding of its building blocks (cortical microcircuits), and their underlying computational principles is thus of paramount interest. To this end, we need reproducible computational models that can be analyzed, modified, extended and quantitatively compared. In this study, we further that aim by providing a replication of a seminal cortical column model. This model consists of noisy Hodgkin-Huxley neurons connected by dynamic synapses, whose connectivity scheme is based on empirical findings from intracellular recordings. Our analysis confirms the key original finding that the specific, data-based connectivity structure enhances the computational performance compared to a variety of alternatively structured control circuits. For this comparison, we use tasks based on spike patterns and rates that require the systems not only to have simple classification capabilities, but also to retain information over time and to be able to compute nonlinear functions. Going beyond the scope of the original study, we demonstrate that this finding is independent of the complexity of the neuron model, which further strengthens the argument that it is the connectivity which is crucial. Finally, a detailed analysis of the memory capabilities of the circuits reveals a stereotypical memory profile common across all circuit variants. Notably, the circuit with laminar structure does not retain stimulus any longer than any other circuit type. We therefore conclude that the model's computational advantage lies in a sharper representation of the stimuli.

Stochastic epidemiological model: Simulations of the SARS-CoV-2 spreading in Mexico.

In this paper we model the spreading of the SARS-CoV-2 in Mexico by introducing a new stochastic approximation constructed from first principles, where the number of new infected individuals caused by a single infectious individual per unit time (a day), is a random variable of a time-dependent Poisson distribution. The model, structured on the basis of a Latent-Infectious-(Recovered or Deceased) (LI(RD)) compartmental approximation together with a modulation of the mean number of new infections (the Poisson parameters), provides a good tool to study theoretical and real scenarios.

Unsupervised Learning and Clustered Connectivity Enhance Reinforcement Learning in Spiking Neural Networks.

Reinforcement learning is a paradigm that can account for how organisms learn to adapt their behavior in complex environments with sparse rewards. To partition an environment into discrete states, implementations in spiking neuronal networks typically rely on input architectures involving place cells or receptive fields specified ad hoc by the researcher. This is problematic as a model for how an organism can learn appropriate behavioral sequences in unknown environments, as it fails to account for the unsupervised and self-organized nature of the required representations. Additionally, this approach presupposes knowledge on the part of the researcher on how the environment should be partitioned and represented and scales poorly with the size or complexity of the environment. To address these issues and gain insights into how the brain generates its own task-relevant mappings, we propose a learning architecture that combines unsupervised learning on the input projections with biologically motivated clustered connectivity within the representation layer. This combination allows input features to be mapped to clusters; thus the network self-organizes to produce clearly distinguishable activity patterns that can serve as the basis for reinforcement learning on the output projections. On the basis of the MNIST and Mountain Car tasks, we show that our proposed model performs better than either a comparable unclustered network or a clustered network with static input projections. We conclude that the combination of unsupervised learning and clustered connectivity provides a generic representational substrate suitable for further computation.

Identification of multidimensional Boolean patterns in microbial communities.

BACKGROUND: Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches. RESULTS: We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data. CONCLUSIONS: The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities. Video Abstract.

Passing the Message: Representation Transfer in Modular Balanced Networks.

Neurobiological systems rely on hierarchical and modular architectures to carry out intricate computations using minimal resources. A prerequisite for such systems to operate adequately is the capability to reliably and efficiently transfer information across multiple modules. Here, we study the features enabling a robust transfer of stimulus representations in modular networks of spiking neurons, tuned to operate in a balanced regime. To capitalize on the complex, transient dynamics that such networks exhibit during active processing, we apply reservoir computing principles and probe the systems' computational efficacy with specific tasks. Focusing on the comparison of random feed-forward connectivity and biologically inspired topographic maps, we find that, in a sequential set-up, structured projections between the modules are strictly necessary for information to propagate accurately to deeper modules. Such mappings not only improve computational performance and efficiency, they also reduce response variability, increase robustness against interference effects, and boost memory capacity. We further investigate how information from two separate input streams is integrated and demonstrate that it is more advantageous to perform non-linear computations on the input locally, within a given module, and subsequently transfer the result downstream, rather than transferring intermediate information and performing the computation downstream. Depending on how information is integrated early on in the system, the networks achieve similar task-performance using different strategies, indicating that the dimensionality of the neural responses does not necessarily correlate with nonlinear integration, as predicted by previous studies. These findings highlight a key role of topographic maps in supporting fast, robust, and accurate neural communication over longer distances. Given the prevalence of such structural feature, particularly in the sensory systems, elucidating their functional purpose remains an important challenge toward which this work provides relevant, new insights. At the same time, these results shed new light on important requirements for designing functional hierarchical spiking networks.

Synaptic patterning and the timescales of cortical dynamics.

Neocortical circuits, as large heterogeneous recurrent networks, can potentially operate and process signals at multiple timescales, but appear to be differentially tuned to operate within certain temporal receptive windows. The modular and hierarchical organization of this selectivity mirrors anatomical and physiological relations throughout the cortex and is likely determined by the regional electrochemical composition. Being consistently patterned and actively regulated, the expression of molecules involved in synaptic transmission constitutes the most significant source of laminar and regional variability. Due to their complex kinetics and adaptability, synapses form a natural primary candidate underlying this regional temporal selectivity. The ability of cortical networks to reflect the temporal structure of the sensory environment can thus be regulated by evolutionary and experience-dependent processes.

Closed Loop Interactions between Spiking Neural Network and Robotic Simulators Based on MUSIC and ROS.

In order to properly assess the function and computational properties of simulated neural systems, it is necessary to account for the nature of the stimuli that drive the system. However, providing stimuli that are rich and yet both reproducible and amenable to experimental manipulations is technically challenging, and even more so if a closed-loop scenario is required. In this work, we present a novel approach to solve this problem, connecting robotics and neural network simulators. We implement a middleware solution that bridges the Robotic Operating System (ROS) to the Multi-Simulator Coordinator (MUSIC). This enables any robotic and neural simulators that implement the corresponding interfaces to be efficiently coupled, allowing real-time performance for a wide range of configurations. This work extends the toolset available for researchers in both neurorobotics and computational neuroscience, and creates the opportunity to perform closed-loop experiments of arbitrary complexity to address questions in multiple areas, including embodiment, agency, and reinforcement learning.

Spatial distribution of anti-rabies post-exposure treatments associated with the decentralization process in Belo Horizonte, 2007 to 2011

Cases of canine attacks on people are reported because of the proximity of the dog to the households in several Brazilian cities. In the present study, we aim to evaluate post-exposure anti-rabies treatments with canine accidents between the years 2007 to 2011 in Belo Horizonte - MG. Duly notified data were obtained from the National System of Notifiable Diseases (SINAN). The spatial characteristics of the cases during the period of the study referred to the neighborhoods and the nine sanitary districts of the municipality of Belo Horizonte - MG. For georeferencing and spatial analysis, we used the software Maporama to identify the coordinates and the Geographic Information System ArcGIS for mapping. Considering the 6.153 prophylactic services that were georeferenced, the Norte, Venda Nova, Leste, and Centro Sul regions were highlighted due to the higher frequency of registered cases. It is suggested that an integrative action focused on canine population control, health education and epidemiological surveillance studies could contribute to the reduction of canine aggression cases.

Dynamic stability of sequential stimulus representations in adapting neuronal networks.

The ability to acquire and maintain appropriate representations of time-varying, sequential stimulus events is a fundamental feature of neocortical circuits and a necessary first step toward more specialized information processing. The dynamical properties of such representations depend on the current state of the circuit, which is determined primarily by the ongoing, internally generated activity, setting the ground state from which input-specific transformations emerge. Here, we begin by demonstrating that timing-dependent synaptic plasticity mechanisms have an important role to play in the active maintenance of an ongoing dynamics characterized by asynchronous and irregular firing, closely resembling cortical activity in vivo. Incoming stimuli, acting as perturbations of the local balance of excitation and inhibition, require fast adaptive responses to prevent the development of unstable activity regimes, such as those characterized by a high degree of population-wide synchrony. We establish a link between such pathological network activity, which is circumvented by the action of plasticity, and a reduced computational capacity. Additionally, we demonstrate that the action of plasticity shapes and stabilizes the transient network states exhibited in the presence of sequentially presented stimulus events, allowing the development of adequate and discernible stimulus representations. The main feature responsible for the increased discriminability of stimulus-driven population responses in plastic networks is shown to be the decorrelating action of inhibitory plasticity and the consequent maintenance of the asynchronous irregular dynamic regime both for ongoing activity and stimulus-driven responses, whereas excitatory plasticity is shown to play only a marginal role.

Liquid computing on and off the edge of chaos with a striatal microcircuit.

In reinforcement learning theories of the basal ganglia, there is a need for the expected rewards corresponding to relevant environmental states to be maintained and modified during the learning process. However, the representation of these states that allows them to be associated with reward expectations remains unclear. Previous studies have tended to rely on pre-defined partitioning of states encoded by disjunct neuronal groups or sparse topological drives. A more likely scenario is that striatal neurons are involved in the encoding of multiple different states through their spike patterns, and that an appropriate partitioning of an environment is learned on the basis of task constraints, thus minimizing the number of states involved in solving a particular task. Here we show that striatal activity is sufficient to implement a liquid state, an important prerequisite for such a computation, whereby transient patterns of striatal activity are mapped onto the relevant states. We develop a simple small scale model of the striatum which can reproduce key features of the experimentally observed activity of the major cell types of the striatum. We then use the activity of this network as input for the supervised training of four simple linear readouts to learn three different functions on a plane, where the network is stimulated with the spike coded position of the agent. We discover that the network configuration that best reproduces striatal activity statistics lies on the edge of chaos and has good performance on all three tasks, but that in general, the edge of chaos is a poor predictor of network performance.

Remissäo de insuficiência cardíaca através de correçäo endoluminal de fístula arteriovenosa femoral com o uso de stent recoberto / Remission of heart failure through endoluminal repair of femoral arteriovenous fistula with the use of a covered stent

We report the case of a 21-year-old male with high-output heart failure due to a femoral arteriovenous fistula caused by a firearm wound. A new balloon expandable stent covered with polytetrafluorethylene was implanted in the artery to occlude the arteriovenous fistula. The fistula was immediately occluded and the artery remained patent. On the following day, the patient felt much better, with no symptoms of heart failure. Additional follow-up is required to assure the usefulness of this less invasive procedure in the treatment of arteriovenous fistulas