Engineering calcium signaling of astrocytes for neural-molecular computing logic gates.

This paper proposes the use of astrocytes to realize Boolean logic gates, through manipulation of the threshold of [Formula: see text] ion flows between the cells based on the input signals. Through wet-lab experiments that engineer the astrocytes cells with pcDNA3.1-hGPR17 genes as well as chemical compounds, we show that both AND and OR gates can be implemented by controlling [Formula: see text] signals that flow through the population. A reinforced learning platform is also presented in the paper to optimize the [Formula: see text] activated level and time slot of input signals [Formula: see text] into the gate. This design platform caters for any size and connectivity of the cell population, by taking into consideration the delay and noise produced from the signalling between the cells. To validate the effectiveness of the reinforced learning platform, a [Formula: see text] signalling simulator was used to simulate the signalling between the astrocyte cells. The results from the simulation show that an optimum value for both the [Formula: see text] activated level and time slot of input signals [Formula: see text] is required to achieve up to 90% accuracy for both the AND and OR gates. Our method can be used as the basis for future Neural-Molecular Computing chips, constructed from engineered astrocyte cells, which can form the basis for a new generation of brain implants

Biocomputing Model Using Tripartite Synapses Provides Reliable Neuronal Logic Gating with Spike Pattern Diversity

Biocomputing technologies exploit biological communication mechanisms involving cell-cell signal propagation to perform computations. Researchers recently worked toward realising logic gates made by neurons to develop novel devices such as organic neuroprostheses or brain implants made by cells, herein termed living implants. Several challenges arise from this approach, mainly associated with the stochastic nature and noise of neuronal communication. Since astrocytes play a crucial role in the regulation of neurons activity, there is a possibility whereby astrocytes can be engineered to control synapses favouring reliable biocomputing. This work proposes a mathematical model of neuronal logic gates involving neurons and astrocytes, realising OR and AND gating. We use a shallow coupling of both the Izhikevich and Postnov models to characterise gating responses with spike pattern variability and astrocyte synaptic regulation. Logic operation error ratio and accuracy assess the AND and OR gates' performances at different synaptic Gaussian noise levels. Our results demonstrate that the astrocyte regulating activity can effectively be used as a denoising mechanism, paving the way for highly reliable biocomputing implementations.Comment: Submitted for journal publication 202

Biocomputing Model Using Tripartite Synapses Provides Reliable Neuronal Logic Gating with Spike Pattern Diversity.

Biocomputing technologies exploit biological communication mechanisms involving cell-cell signal propagation to perform computations. Researchers recently worked toward realising logic gates made by neurons to develop novel devices such as organic neuroprostheses or brain implants made by cells, herein termed living implants. Several challenges arise from this approach, mainly associated with the stochastic nature and noise of neuronal communication. Since astrocytes play a crucial role in the regulation of neurons activity, there is a possibility whereby astrocytes can be engineered to control synapses favouring reliable biocomputing. This work proposes a mathematical model of neuronal logic gates involving neurons and astrocytes, realising OR and AND gating. We use a shallow coupling of both the Izhikevich and Postnov models to characterise gating responses with spike pattern variability and astrocyte synaptic regulation. Logic operation error ratio and accuracy assess the AND and OR gates' performances at different synaptic Gaussian noise levels. Our results demonstrate that the astrocyte regulating activity can effectively be used as a denoising mechanism, paving the way for highly reliable biocomputing implementations

Astrocyte control bursting mode of spiking neuron network with memristor-implemented plasticity

A mathematical model of a spiking neuron network accompanied by astrocytes is considered. The network is composed of excitatory and inhibitory neurons with synaptic connections supplied by a memristor-based model of plasticity. Another mechanism for changing the synaptic connections involves astrocytic regulations using the concept of tripartite synapses. In the absence of memristor-based plasticity, the connections between these neurons drive the network dynamics into a burst mode, as observed in many experimental neurobiological studies when investigating living networks in neuronal cultures. The memristive plasticity implementing synaptic plasticity in inhibitory synapses results in a shift in network dynamics towards an asynchronous mode. Next,it is found that accounting for astrocytic regulation in glutamatergic excitatory synapses enable the restoration of 'normal' burst dynamics. The conditions and parameters of such astrocytic regulation's impact on burst dynamics established

What Really is `Molecule' in Molecular Communications? The Quest for Physics of Particle-based Information Carriers

Molecular communication, as implied by its name, uses molecules as information carriers for communication between objects. It has an advantage over traditional electromagnetic-wave-based communication in that molecule-based systems could be biocompatible, operable in challenging environments, and energetically undemanding. Consequently, they are envisioned to have a broad range of applications, such as in the Internet of Bio-nano Things, targeted drug delivery, and agricultural monitoring. Despite the rapid development of the field, with an increasing number of theoretical models and experimental testbeds established by researchers, a fundamental aspect of the field has often been sidelined, namely, the nature of the molecule in molecular communication. The potential information molecules could exhibit a wide range of properties, making them require drastically different treatments when being modeled and experimented upon. Therefore, in this paper, we delve into the intricacies of commonly used information molecules, examining their fundamental physical characteristics, associated communication systems, and potential applications in a more realistic manner, focusing on the influence of their own properties. Through this comprehensive survey, we aim to offer a novel yet essential perspective on molecular communication, thereby bridging the current gap between theoretical research and real-world applications

Astrocytes in modulating subcellular, cellular and intercellular molecular neuronal communication

Astrocytes are one of the most abundant cell types in our brain. They modulate the brain homeostasis and play a role in the synaptic signalling and thus the molecular propagation inside the brain. Moreover, they form communication networks that co-localise with the neuronal networks with comparable topological complexity. There is an increasing piece of evidence that astrocytes are important in plasticity and learning from the level of the single synapse to the entire network. Moreover, several diseases are molecular communications on different scales from the synaptic to network level.acceptedVersionPeer reviewe

Dual Ionic Transport Using Ca²⁺and Na²⁺ Signaling for Molecular Communication Systems

Astrocytes have the ability to modulate neuronal communication by regulating various levels of ionic concentrations. The development of models for molecular communication ought to investigate the utilisation of various ionic transportation mechanisms, with the aim of enhancing performance and biocompatibility, thereby facilitating co-existence within cellular tissues. In this study, we suggest the utilisation of both Ca 2+ and Na + ions to investigate the non-linearities of propagation in cellular tissues for MC. In this study, we also investigated the impact of various ionic transport mechanisms, including the sodium-calcium exchanger, sodium-potassium pump, and calcium pump, to assess their impact on the intracellular propagation of Ca 2+. We analysed four communication metrics metrics, namely channel capacity, bit error rate (BER), communication gain, and signal-to-noise ratio, to evaluate the effects of the transport mechanisms on the communication channel

Microfluidic-based Bacterial Molecular Computing on a Chip

Biocomputing systems based on engineered bacteria can lead to novel tools for environmental monitoring and detection of metabolic diseases. In this paper, we propose a Bacterial Molecular Computing on a Chip (BMCoC) using microfluidic and electrochemical sensing technologies. The computing can be flexibly integrated into the chip, but we focus on engineered bacterial AND Boolean logic gate and ON-OFF switch sensors that produces secondary signals to change the pH and dissolved oxygen concentrations. We present a prototype with experimental results that shows the electrochemical sensors can detect small pH and dissolved oxygen concentration changes created by the engineered bacterial populations’ molecular signals. Additionally, we present a theoretical model analysis of the BMCoC computation reliability when subjected to unwanted effects, i.e., molecular signal delays and noise, and electrochemical sensors threshold settings that are based on either standard or blind detectors. Our numerical analysis found that the variations in the production delay and the molecular output signal concentration can impact on the computation reliability for the AND logic gate and ON-OFF switch. The molecular communications of synthetic engineered cells for logic gates integrated with sensing systems can lead to a new breed of biochips that can be used for numerous diagnostic applications

Parallel computing for brain simulation

[Abstract] Background: The human brain is the most complex system in the known universe, it is therefore one of the greatest mysteries. It provides human beings with extraordinary abilities. However, until now it has not been understood yet how and why most of these abilities are produced. Aims: For decades, researchers have been trying to make computers reproduce these abilities, focusing on both understanding the nervous system and, on processing data in a more efficient way than before. Their aim is to make computers process information similarly to the brain. Important technological developments and vast multidisciplinary projects have allowed creating the first simulation with a number of neurons similar to that of a human brain. Conclusion: This paper presents an up-to-date review about the main research projects that are trying to simulate and/or emulate the human brain. They employ different types of computational models using parallel computing: digital models, analog models and hybrid models. This review includes the current applications of these works, as well as future trends. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). Their most outstanding characteristics are summarized and the latest advances and future plans are presented. In addition, this review points out the importance of considering not only neurons: Computational models of the brain should also include glial cells, given the proven importance of astrocytes in information processing.Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; GRC2014/049Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; R2014/039Instituto de Salud Carlos III; PI13/0028

Principles for the design of multicellular engineered living systems

Remarkable progress in bioengineering over the past two decades has enabled the formulation of fundamental design principles for a variety of medical and non-medical applications. These advancements have laid the foundation for building multicellular engineered living systems (M-CELS) from biological parts, forming functional modules integrated into living machines. These cognizant design principles for living systems encompass novel genetic circuit manipulation, self-assembly, cell–cell/matrix communication, and artificial tissues/organs enabled through systems biology, bioinformatics, computational biology, genetic engineering, and microfluidics. Here, we introduce design principles and a blueprint for forward production of robust and standardized M-CELS, which may undergo variable reiterations through the classic design-build-test-debug cycle. This Review provides practical and theoretical frameworks to forward-design, control, and optimize novel M-CELS. Potential applications include biopharmaceuticals, bioreactor factories, biofuels, environmental bioremediation, cellular computing, biohybrid digital technology, and experimental investigations into mechanisms of multicellular organisms normally hidden inside the “black box” of living cells