Estimating integrated information in bidirectional neuron-astrocyte communication.

There is growing evidence that suggests the importance of astrocytes as elements for neural information processing through the modulation of synaptic transmission. A key aspect of this problem is understanding the impact of astrocytes in the information carried by compound events in neurons across time. In this paper, we investigate how the astrocytes participate in the information integrated by individual neurons in an ensemble through the measurement of "integrated information." We propose a computational model that considers bidirectional communication between astrocytes and neurons through glutamate-induced calcium signaling. Our model highlights the role of astrocytes in information processing through dynamical coordination. Our findings suggest that the astrocytic feedback promotes synergetic influences in the neural communication, which is maximized when there is a balance between excess correlation and spontaneous spiking activity. The results were further linked with additional measures such as net synergy and mutual information. This result reinforces the idea that astrocytes have integrative properties in communication among neurons.

Integrated Information in the Spiking-Bursting Stochastic Model.

Integrated information has been recently suggested as a possible measure to identify a necessary condition for a system to display conscious features. Recently, we have shown that astrocytes contribute to the generation of integrated information through the complex behavior of neuron-astrocyte networks. Still, it remained unclear which underlying mechanisms governing the complex behavior of a neuron-astrocyte network are essential to generating positive integrated information. This study presents an analytic consideration of this question based on exact and asymptotic expressions for integrated information in terms of exactly known probability distributions for a reduced mathematical model (discrete-time, discrete-state stochastic model) reflecting the main features of the "spiking-bursting" dynamics of a neuron-astrocyte network. The analysis was performed in terms of the empirical "whole minus sum" version of integrated information in comparison to the "decoder based" version. The "whole minus sum" information may change sign, and an interpretation of this transition in terms of "net synergy" is available in the literature. This motivated our particular interest in the sign of the "whole minus sum" information in our analytical considerations. The behaviors of the "whole minus sum" and "decoder based" information measures are found to bear a lot of similarity-they have mutual asymptotic convergence as time-uncorrelated activity increases, and the sign transition of the "whole minus sum" information is associated with a rapid growth in the "decoder based" information. The study aims at creating a theoretical framework for using the spiking-bursting model as an analytically tractable reference point for applying integrated information concepts to systems exhibiting similar bursting behavior. The model can also be of interest as a new discrete-state test bench for different formulations of integrated information.

Brain aging and garbage cleaning : Modelling the role of sleep, glymphatic system, and microglia senescence in the propagation of inflammaging.

Brain aging is a complex process involving many functions of our body and described by the interplay of a sleep pattern and changes in the metabolic waste concentration regulated by the microglial function and the glymphatic system. We review the existing modelling approaches to this topic and derive a novel mathematical model to describe the crosstalk between these components within the conceptual framework of inflammaging. Analysis of the model gives insight into the dynamics of garbage concentration and linked microglial senescence process resulting from a normal or disrupted sleep pattern, hence, explaining an underlying mechanism behind healthy or unhealthy brain aging. The model incorporates accumulation and elimination of garbage, induction of glial activation by garbage, and glial senescence by over-activation, as well as the production of pro-inflammatory molecules by their senescence-associated secretory phenotype (SASP). Assuming that insufficient sleep leads to the increase of garbage concentration and promotes senescence, the model predicts that if the accumulation of senescent glia overcomes an inflammaging threshold, further progression of senescence becomes unstoppable even if a normal sleep pattern is restored. Inverting this process by "rejuvenating the brain" is only possible via a reset of concentration of senescent glia below this threshold. Our model approach enables analysis of space-time dynamics of senescence, and in this way, we show that heterogeneous patterns of inflammation will accelerate the propagation of senescence profile through a network, confirming a negative effect of heterogeneity.

The Human Body as a Super Network: Digital Methods to Analyze the Propagation of Aging.

Biological aging is a complex process involving multiple biological processes. These can be understood theoretically though considering them as individual networks-e.g., epigenetic networks, cell-cell networks (such as astroglial networks), and population genetics. Mathematical modeling allows the combination of such networks so that they may be studied in unison, to better understand how the so-called "seven pillars of aging" combine and to generate hypothesis for treating aging as a condition at relatively early biological ages. In this review, we consider how recent progression in mathematical modeling can be utilized to investigate aging, particularly in, but not exclusive to, the context of degenerative neuronal disease. We also consider how the latest techniques for generating biomarker models for disease prediction, such as longitudinal analysis and parenclitic analysis can be applied to as both biomarker platforms for aging, as well as to better understand the inescapable condition. This review is written by a highly diverse and multi-disciplinary team of scientists from across the globe and calls for greater collaboration between diverse fields of research.

Astrocyte-induced positive integrated information in neuron-astrocyte ensembles.

Integrated information is a quantitative measure from information theory of how tightly all parts of a system are interconnected in terms of information exchange. In this study we show that astrocytes, playing an important role in regulation of information transmission between neurons, may contribute to a generation of positive integrated information in neuronal ensembles. Analytically and numerically we show that the presence of astrocytic regulation of neurotransmission may be essential for this information attribute in neuroastrocytic ensembles. Moreover, the proposed "spiking-bursting" mechanism of generating positive integrated information is shown to be generic and not limited to neuron-astrocyte networks and is given a complete analytic description.

Synthetic biology routes to bio-artificial intelligence.

The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular 'teachers' and 'students' is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance. In addition to designed SGNs, we also consider the option to establish conditions in which a population of SGNs can evolve diversity in order to better contend with complex input data. Finally, we compare recent ethical concerns in the field of artificial intelligence (AI) and the future challenges raised by bio-artificial intelligence (BI).

Spatiotemporal dynamics of distributed synthetic genetic circuits.

We propose and study models of two distributed synthetic gene circuits, toggle-switch and oscillator, each split between two cell strains and coupled via quorum-sensing signals. The distributed toggle switch relies on mutual repression of the two strains, and oscillator is comprised of two strains, one of which acts as an activator for another that in turn acts as a repressor. Distributed toggle switch can exhibit mobile fronts, switching the system from the weaker to the stronger spatially homogeneous state. The circuit can also act as a biosensor, with the switching front dynamics determined by the properties of an external signal. Distributed oscillator system displays another biosensor functionality: oscillations emerge once a small amount of one cell strain appears amid the other, present in abundance. Distribution of synthetic gene circuits among multiple strains allows one to reduce crosstalk among different parts of the overall system and also decrease the energetic burden of the synthetic circuit per cell, which may allow for enhanced functionality and viability of engineered cells.

Anderson attractors in active arrays.

In dissipationless linear media, spatial disorder induces Anderson localization of matter, light, and sound waves. The addition of nonlinearity causes interaction between the eigenmodes, which results in a slow wave diffusion. We go beyond the dissipationless limit of Anderson arrays and consider nonlinear disordered systems that are subjected to the dissipative losses and energy pumping. We show that the Anderson modes of the disordered Ginsburg-Landau lattice possess specific excitation thresholds with respect to the pumping strength. When pumping is increased above the threshold for the band-edge modes, the lattice dynamics yields an attractor in the form of a stable multi-peak pattern. The Anderson attractor is the result of a joint action by the pumping-induced mode excitation, nonlinearity-induced mode interactions, and dissipative stabilization. The regimes of Anderson attractors can be potentially realized with polariton condensates lattices, active waveguide or cavity-QED arrays.

Multi-input distributed classifiers for synthetic genetic circuits.

For practical construction of complex synthetic genetic networks able to perform elaborate functions it is important to have a pool of relatively simple modules with different functionality which can be compounded together. To complement engineering of very different existing synthetic genetic devices such as switches, oscillators or logical gates, we propose and develop here a design of synthetic multi-input classifier based on a recently introduced distributed classifier concept. A heterogeneous population of cells acts as a single classifier, whose output is obtained by summarizing the outputs of individual cells. The learning ability is achieved by pruning the population, instead of tuning parameters of an individual cell. The present paper is focused on evaluating two possible schemes of multi-input gene classifier circuits. We demonstrate their suitability for implementing a multi-input distributed classifier capable of separating data which are inseparable for single-input classifiers, and characterize performance of the classifiers by analytical and numerical results. The simpler scheme implements a linear classifier in a single cell and is targeted at separable classification problems with simple class borders. A hard learning strategy is used to train a distributed classifier by removing from the population any cell answering incorrectly to at least one training example. The other scheme implements a circuit with a bell-shaped response in a single cell to allow potentially arbitrary shape of the classification border in the input space of a distributed classifier. Inseparable classification problems are addressed using soft learning strategy, characterized by probabilistic decision to keep or discard a cell at each training iteration. We expect that our classifier design contributes to the development of robust and predictable synthetic biosensors, which have the potential to affect applications in a lot of fields, including that of medicine and industry.

Distributed classifier based on genetically engineered bacterial cell cultures.

We describe a conceptual design of a distributed classifier formed by a population of genetically engineered microbial cells. The central idea is to create a complex classifier from a population of weak or simple classifiers. We create a master population of cells with randomized synthetic biosensor circuits that have a broad range of sensitivities toward chemical signals of interest that form the input vectors subject to classification. The randomized sensitivities are achieved by constructing a library of synthetic gene circuits with randomized control sequences (e.g., ribosome-binding sites) in the front element. The training procedure consists in reshaping of the master population in such a way that it collectively responds to the "positive" patterns of input signals by producing above-threshold output (e.g., fluorescent signal), and below-threshold output in case of the "negative" patterns. The population reshaping is achieved by presenting sequential examples and pruning the population using either graded selection/counterselection or by fluorescence-activated cell sorting (FACS). We demonstrate the feasibility of experimental implementation of such system computationally using a realistic model of the synthetic sensing gene circuits.