Neuron-astrocyte Interaction Research Articles

Astrocytes as a mechanism for contextually-guided network dynamics and function.

Astrocytes are a ubiquitous and enigmatic type of non-neuronal cell and are found in the brain of all vertebrates. While traditionally viewed as being supportive of neurons, it is increasingly recognized that astrocytes play a more direct and active role in brain function and neural computation. On account of their sensitivity to a host of physiological covariates and ability to modulate neuronal activity and connectivity on slower time scales, astrocytes may be particularly well poised to modulate the dynamics of neural circuits in functionally salient ways. In the current paper, we seek to capture these features via actionable abstractions within computational models of neuron-astrocyte interaction. Specifically, we engage how nested feedback loops of neuron-astrocyte interaction, acting over separated time-scales, may endow astrocytes with the capability to enable learning in context-dependent settings, where fluctuations in task parameters may occur much more slowly than within-task requirements. We pose a general model of neuron-synapse-astrocyte interaction and use formal analysis to characterize how astrocytic modulation may constitute a form of meta-plasticity, altering the ways in which synapses and neurons adapt as a function of time. We then embed this model in a bandit-based reinforcement learning task environment, and show how the presence of time-scale separated astrocytic modulation enables learning over multiple fluctuating contexts. Indeed, these networks learn far more reliably compared to dynamically homogeneous networks and conventional non-network-based bandit algorithms. Our results fuel the notion that neuron-astrocyte interactions in the brain benefit learning over different time-scales and the conveyance of task-relevant contextual information onto circuit dynamics.

Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease.

The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer's disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3×Tg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD.

A 3D human co-culture to model neuron-astrocyte interactions in tauopathies

BackgroundIntraneuronal tau aggregation is the major pathological hallmark of neurodegenerative tauopathies. It is now generally acknowledged that tau aggregation also affects astrocytes in a cell non-autonomous manner. However, mechanisms involved are unclear, partly because of the lack of models that reflect the situation in the human tauopathy brain. To accurately model neuron-astrocyte interaction in tauopathies, there is a need for a model that contains both human neurons and human astrocytes, intraneuronal tau pathology and mimics the three-dimensional architecture of the brain.ResultsHere we established a novel 100–200 µm thick 3D human neuron/astrocyte co-culture model of tau pathology, comprising homogenous populations of hiPSC-derived neurons and primary human astrocytes in microwell format. Using confocal, electron and live microscopy, we validate the procedures by showing that neurons in the 3D co-culture form pre- and postsynapses and display spontaneous calcium transients within 4 weeks. Astrocytes in the 3D co-culture display bipolar and stellate morphologies with extensive processes that ensheath neuronal somas, spatially align with axons and dendrites and can be found perisynaptically. The complex morphology of astrocytes and the interaction with neurons in the 3D co-culture mirrors that in the human brain, indicating the model’s potential to study physiological and pathological neuron-astrocyte interaction in vitro. Finally, we successfully implemented a methodology to introduce seed-independent intraneuronal tau aggregation in the 3D co-culture, enabling study of neuron-astrocyte interaction in early tau pathogenesis.ConclusionsAltogether, these data provide proof-of-concept for the utility of this rapid, miniaturized, and standardized 3D model for cell type-specific manipulations, such as the intraneuronal pathology that is associated with neurodegenerative disorders.

Cover Image, Volume 71, Issue 4

Cover Illustration: The 3D reconstruction of super-resolution immunofluorescent confocal image shows that glutamate transporter 1 (GLT1; green)-labeled astrocytic processes enwrap neurons labeled by microtubule-associated protein 2 (MAP2, red; nuclei, blue) in primary mouse cortical glia-neuron mix culture. The close proximity of MAP2-GLT1 indicates the neuron-astrocyte interaction for maintaining glutamate homeostasis and neuronal activity. (See Huang Y-J, et al. https://doi.org/10.1002/glia.24326)

Astrocytic aryl hydrocarbon receptor mediates chronic kidney disease-associated mental disorders involving GLT1 hypofunction and neuronal activity enhancement in the mouse brain.

Chronic kidney disease (CKD)-associated mental disorders have been attributed to the excessive accumulation of hemodialysis-resistant indoxyl-3-sulfate (I3S) in the brain. I3S not only induces oxidative stress but is also a potent endogenous agonist of the aryl hydrocarbon receptor (AhR). Here, we investigated the role of AhR in CKD-induced brain disorders using a 5/6 nephrectomy-induced CKD mouse model, which showed increased I3S concentration in both blood and brain, anxiety and impaired novelty recognition, and AhR activation in the anterior cortex. GFAP+ reactive astrocytes were increased accompanied with the reduction of glutamate transporter 1 (GLT1) on perineuronal astrocytic processes (PAPs) in the anterior cingulate cortex (ACC) in CKD mice, and these alterations were attenuated in both neural lineage-specific and astrocyte-specific Ahr conditional knockout mice (nAhrCKO and aAhrCKO). By using chronic I3S treatment in primary astrocytes and glia-neuron (GN) mix cultures to mimic the CKD brain microenvironment, we also found significant reduction of GLT1 expression and activity in an AhR-dependent manner. Chronic I3S treatment induced AhR-dependent pro-oxidant Nox1 and AhR-independent anti-oxidant HO-1 expressions. Notably, AhR mediates chronic I3S-induced neuronal activity enhancement and synaptotoxicity in GN mix, not neuron-enriched cortical culture. In CKD mice, neuronal activity enhancement was observed in ACC and hippocampal CA1, and these responses were abrogated by both nAhrCKO and aAhrCKO. Finally, intranasal AhR antagonist CH-223191 administration significantly ameliorated the GLT1/PAPs reduction, increase in c-Fos+ neurons, and memory impairment in the CKD mice. Thus, astrocytic AhR plays a crucial role in the CKD-induced disturbance of neuron-astrocyte interaction and mental disorders.

Co-culture platform for neuron-astrocyte interaction using optogenetic modulation.

For decades, the role of glial cells has attracted attention in the neuroscience field. Particularly, although the astrocyte is the most abundant glial cell type, it was believed to function as a passive support cell. However, recent evidence suggests that astrocytes actively release various gliotransmitters and signaling entities that regulate the excitability of pre-and post-synaptic neurons in the brain. In this study, we optimized the ratio of astrocytes and neurons to investigate the interaction between astrocytes and neurons. To this end, postnatal day 0-1 rodent hippocampi were dissociated and cultured. The neuron-astrocyte ratio was monitored for up to 3weeks after treating the cultures with 0, 1, and 5µM of cytosine arabinoside (Ara-C) at DIV 2. Subsequently, from postnatal transgenic (TG) mouse expressing ChR2 on astrocytes, hippocampi were cultured on the microelectrode array (MEA) with the desired neuron-astrocyte ratio. The astrocyte was irradiated using a 473nm blue laser for 30s in a cycle of 10Hz and electrophysiological recording was performed to verify the activities of neurons induced by the stimulated astrocytes. Astrocytes and neurons in both co-cultures increased at an identical ratio when treated with 1µM Ara-C, whereas they decreased significantly when treated with 5µM Ara-C. Particularly, the laser-stimulated astrocytes induced an increase in the frequency of neuronal activities and lasted after illumination. The proposed co-culture platform is expected to be used in experiments to investigate the network between astrocytes and neurons in vitro.

A Digital Realization of Neuroglial Interaction Model and Its Network Structure

Astrocyte cells, the most existing abundant cells in central nervous system, play an essential role in modulating the neuronal activities, information processing, and regulating the synaptic plasticity through calcium (Ca2+) fluctuations of ions hemostasis by using a feedback mechanism. The pathophysiological and hypersynchronous neuronal activity can lead to the epileptic seizures, which is known as one of the neurodegenerative disorders in the field of neuroscience. This paper presents a modified neuron-astrocyte interaction (tripartite synapse) model based on leaky and integrate fire neuron and the astrocyte-synapse models using an area-efficient hardware approach called stochastic computing paradigm. The proposed model is synthesized physically on field-programmable gate array as a proof of concept. The implementation results of the presented model can mimic the bidirectional communication in biological minimal network of pre-postsynaptic and Ca2+-based model for astrocyte with considerably lower hardware cost. The influence of astrocytes on neural network behavioral has been investigated by providing a proper feedback mechanism and considering the role of gap junction coupling and the various coefficients on desynchronizing the impaired synchronization of the coupled neurons.

Neuron-Astrocyte Interactions in Parkinson's Disease.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future.

Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow

Cell-to-cell communications are critical determinants of pathophysiological phenotypes, but methodologies for their systematic elucidation are lacking. Herein, we propose an approach for the Systematic Elucidation and Assessment of Regulatory Cell-to-cell Interaction Networks (SEARCHIN) to identify ligand-mediated interactions between distinct cellular compartments. To test this approach, we selected a model of amyotrophic lateral sclerosis (ALS), in which astrocytes expressing mutant superoxide dismutase-1 (mutSOD1) kill wild-type motor neurons (MNs) by an unknown mechanism. Our integrative analysis that combines proteomics and regulatory network analysis infers the interaction between astrocyte-released amyloid precursor protein (APP) and death receptor-6 (DR6) on MNs as the top predicted ligand-receptor pair. The inferred deleterious role of APP and DR6 is confirmed in vitro in models of ALS. Moreover, the DR6 knockdown in MNs of transgenic mutSOD1 mice attenuates the ALS-like phenotype. Our results support the usefulness of integrative, systems biology approach to gain insights into complex neurobiological disease processes as in ALS and posit that the proposed methodology is not restricted to this biological context and could be used in a variety of other non-cell-autonomous communication mechanisms.

An investigation on neuron–astrocyte interaction system: network behavior and synchronization

Astrocytes, also described as astroglia, are characteristic star-shaped glial cells in the brain. The important roles of astrocyte such as extracellular regulation, synaptic information regulation, neuronal synchronization and feedback to neural activity, makes the astrocytes play a vital role in the brain disease. This paper investigates the neuron–astrocyte interaction system for evaluating the network behaviors. In this approach, two basic systems are presented for considering the astrocyte controlling effects on desynchronization of the neurons spiking activity. Simulation results proved that by proper selection of the astrocyte coupling parameters in the proposed network, the networking behaviors can be modulated. As a result, when these coupling parameters have suitable values, the neurons behavior in the sample system will be controlled.

Lauric acid promotes neuronal maturation mediated by astrocytes in primary cortical cultures

Previous studies have suggested the potential efficacy of middle chain fatty acids (MCFAs) in the treatment of mood disorders and cognitive dysfunction. MCFAs are metabolized to ketone bodies in astrocytes; however, their effects on neuronal development including neurotrophic factor level are not well-understood. In the present study, we examined the effect of MCFAs on the mRNA expression of growth factors and cytokines in primary cultures of cortical astrocytes. The effect of MCFAs on neuron-astrocyte interaction in neuronal maturation was also determined using co-culture and astrocyte-conditioned medium. Lauric acid (LA) typically increased the mRNA expression of glial-derived neurotrophic factor (Gdnf), interleukin-6 (Il6), and C–C motif chemokine 2 (Ccl2) in astrocytes. LA-induced phosphorylation of extracellular signal-regulated kinase contributed to these changes. In primary cultures of cortical neurons containing astrocytes, LA enhanced the presynaptic protein levels. Astrocyte-conditioned medium after LA treatment also enhanced the presynaptic protein levels in the cortical neuron cultures. These results suggest that LA increase the mRNA expression of GDNF and cytokines in astrocytes, and thereby, enhances the presynaptic maturation.

Astrocyte Expression of Synapse Promoting Genes is Developmentally Regulated by Neuronal and Astrocyte Activity

Astrocytes are crucial regulators of neuronal synapse development and function. In the rodent cortex neurons are arranged in layers, each with stereotyped synaptic connectivity. Cortical astrocytes produce several synapse promoting factors, however, whether they differentially regulate formation of synapses in different layers is unknown. Furthermore, the developmental expression pattern of astrocyte synaptogenic cues, and whether expression is regulated by neuronal or astrocyte activity, is unknown. Here we use genetic mouse models, immunohistochemistry and in situ hybridization to quantify the developmental expression changes of astrocyte-derived synapse promoting genes, such as glypicans and chordin like1, in the mouse visual cortex. The observed expression changes occurred mainly between post-natal days (P) 7 and 14, a time between synapse initiation and maturation, and showed layer specific regulation. For example, glypican4 expression is strongly reduced at P14 in layer (L) 1, while glypican6 expression is increased in deeper layers. Next, perturbing glutamate release from thalamic neurons by knocking out VGlut2 resulted in significant increase in glypican4 expression in L1, while expression of glypican6 decreased in deep layers. Moreover, perturbing astrocyte activity by knocking out IP3R2 resulted in a significant decrease in glypican4 expression, but had no effect on glypican6 expression. Remarkably, neuronal GluA1 AMPAR protein levels in L1 showed correlated expression changes to glypican4 in both neuronal, and astrocyte activity perturbed mice models. To determine the underlying mechanism of astrocyte gene regulation by neuronal and astrocyte activity I have conducted single cell transcriptomic profiling of astrocytes in each of the models. These findings provide insight into neuron-astrocyte interaction as it occurs at the level of the distinct cortical connections, and constitute an important frame work for future studies of astrocyte and synapse development in the cortex.

Neuronal synchronization enhanced by neuron–astrocyte interaction

In this study, we consider the problem of signal processing in neuron–astrocyte networks where the intercellular communication is described on the basis of a tripartite synapse concept. This type of communication involves combined contributions of pre- and postsynaptic neuronal compartments and components of the surrounding astrocyte to the processes of information transmission. Astrocyte-mediated regulation of neuronal activity is considered through the analysis of the response changes in the classical Hodgkin–Huxley model driven by excitatory synaptic current. It is shown that the complicated astrocyte-dependent dynamics of this current can lead to non-trivial changes in individual postsynaptic neuronal activity and, hence, in the cooperative activation of neuronal groups linked by the “astrocyte-mediated bridge”.

Astrocytic modulation of glutamatergic synaptic transmission is reduced in NTS of rats submitted to short-term sustained hypoxia.

Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O2 back to the physiological range. We evaluated the effect of SH (fraction of inspired O2 = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) [-183 ± 122 pA (n = 10) vs. -353 ± 101 pA (n = 10)] and N-methyl-d-aspartate (NMDA) current amplitude [61 ± 10 pA (n = 7) vs. 102 ± 37 pA (n = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA [artificial cerebrospinal fluid (aCSF): -353 ± 101 pA vs. aCSF + FAC: -369 ± 76 pA (n = 10)] and NMDA currents [aCSF: 102 ± 37 pA vs. aCSF + FAC: 108 ± 32 pA (n = 10)]. SH increased AMPA current density [control: -6 ± 3.5 pA/pF (n = 6) vs. SH: -20 ± 12 pA/pF (n = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats. NEW & NOTEWORTHY Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to 1) a reduction in the astrocytic modulation and 2) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats.

Complete Neuron-Astrocyte Interaction Model: Digital Multiplierless Design and Networking Mechanism.

Glial cells, also known as neuroglia or glia, are non-neuronal cells providing support and protection for neurons in the central nervous system (CNS). They also act as supportive cells in the brain. Among a variety of glial cells, the star-shaped glial cells, i.e., astrocytes, are the largest cell population in the brain. The important role of astrocyte such as neuronal synchronization, synaptic information regulation, feedback to neural activity and extracellular regulation make the astrocytes play a vital role in brain disease. This paper presents a modified complete neuron-astrocyte interaction model that is more suitable for efficient and large scale biological neural network realization on digital platforms. Simulation results show that the modified complete interaction model can reproduce biological-like behavior of the original neuron-astrocyte mechanism. The modified interaction model is investigated in terms of digital realization feasibility and cost targeting a low cost hardware implementation. Networking behavior of this interaction is investigated and compared between two cases: i) the neuron spiking mechanism without astrocyte effects, and ii) the effect of astrocyte in regulating the neurons behavior and synaptic transmission via controlling the LTP and LTD processes. Hardware implementation on FPGA shows that the modified model mimics the main mechanism of neuron-astrocyte communication with higher performance and considerably lower hardware overhead cost compared with the original interaction model.

Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron–astrocyte interaction in the dentate gyrus

Childhood trauma is a well-described risk factor for the development of stress-related psychopathology such as posttraumatic stress disorder or depression later in life. Childhood adversity can be modeled in rodents by juvenile stress (JS) protocols, resulting in impaired coping with stressful challenges in adulthood. In the current study, we investigated the long-lasting impact of JS on the expression of molecular factors for glutamate and γ-aminobutyric acid (GABA) uptake and turnover in sublayers of the dentate gyrus (DG) using laser microdissection and quantitative real-time polymerase chain reaction. We observed reduced mRNA expression levels after JS for factors mediating astrocytic glutamate and GABA uptake and degradation. These alterations were prominently observed in the dorsal but not ventral DG granule cell layer, indicating a lasting change in astrocytic GABA and glutamate metabolism that may affect dorsal DG network activity. Indeed, we observed increased inhibition and a lack of facilitation in response to paired-pulse stimulation at short interstimulus intervals in the dorsal DG after JS, while no alterations were evident in basal synaptic transmission or forms of long-term plasticity. The shift in paired-pulse response was mimicked by pharmacologically blocking the astrocytic GABA transporter GAT-3 in naïve animals. Accordingly, reduced expression levels of GAT-3 were confirmed at the protein level in the dorsal granule cell layer of rats stressed in juvenility. Together, these data demonstrate a lasting shift in the excitatory/inhibitory balance of dorsal DG network activity by JS that appears to be mediated by decreased GABA uptake into astrocytes.

Analog implementation of neuron–astrocyte interaction in tripartite synapse

Neural synchronization is considered as an important mechanism for information processing. In addition, recent neurophysiological findings approve that astrocytes adjust the synaptic transmission of neural networks. Motivated by these observations, we develop an analog neuromorphic circuit to implement the tripartite synapse. To model the dynamics of the intracellular calcium waves produced by the astrocytes, we utilize a simplified model which considers the key physiological pathways of neuron---astrocyte communication. Next, using an astrocyte analog circuit, a tripartite synapse circuit is constructed by connecting two modified differential pair integrator neurons and one astrocyte circuits. It is designed and simulated using HSPICE simulator in $$0.35\,\upmu \hbox {m}$$0.35μm standard CMOS technology. The simulation results of the tripartite synapse circuit, demonstrate that astrocyte circuit plays a crucial role in neuronal firing synchronicity from hardware point of view. In this way, astrocyte---neuron collaboration leads to the emergence of synchronous/asynchronous patterns in neural responses. Therefore, it makes possible to have a new circuit in which astrocyte actively contributes in neural information processing.

Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes

Gamma aminobutric acid (GABA) is the major inhibitory neurotransmitter in the adult brain and mechanisms of GABAergic inhibition have been intensely investigated in the past decades. Recent studies provided evidence for an important role of astrocytes in shaping GABAergic currents. One of the most obvious, but yet poorly understood, mechanisms of the cross-talk between GABAergic currents and astrocytes is metabolism including neurotransmitter homeostasis. In particular, how modulation of GABAergic currents by astrocytes depends on key enzymes involved in cellular metabolism remains largely unknown. To address this issue, we have considered two simple models of neuronal culture (NC): nominally astrocyte-free NC and neuronal-astrocytic co-cultures (ANCC). Miniature Inhibitory Postsynaptic Currents (mIPSCs) were recorded in control conditions and in the presence of different enzyme blockers. We report that enrichment of NC with astrocytes results in a marked increase in mIPSC frequency. This enhancement of GABAergic activity was accompanied by increased number of GAD65 and vGAT puncta, indicating that at least a part of the frequency enhancement was due to increased number of synaptic contacts. Inhibition of glutamine synthetase (Glns) (with MSO) strongly reduced mIPSC frequency in ANCC but had no effect in NC. Moreover, treatment of ANCC with inhibitor of glycogen phosphorylase (Gys) (BAYU6751) or with selective inhibitor of astrocytic Krebs cycle, fluoroacetate, resulted in a marked reduction of mIPSC frequency in ANCC having no effect in NC. We conclude that GABAergic synaptic transmission strongly depends on neuron-astrocyte interaction in a manner dependent on key metabolic enzymes as well as on the Krebs cycle.

Multiplier-less digital implementation of neuron–astrocyte signalling on FPGA

Experimental observations have shown that astrocytes are active partner in neural information processing which are mainly carried out by neurons. In this research, we investigate this issue and provide a computationally efficient digital circuit for neuron–astrocyte interactions. The firing dynamics of the neuron is described by Izhikevich model (spiking and bursting activities) and the calcium dynamics of a single astrocyte explained by a proposed model adapted from a functional model introduced by Postnov and colleagues. The new linear model makes it possible to design an efficient multiplier-less hardware architecture for digital implementation of neuron–astrocyte interaction on field-programmable gate array (FPGA). Using the proposed neuron–astrocyte circuit and based on the results of MATLAB simulation, hardware synthesis and FPGA implementation, it is demonstrated that the proposed digital astrocyte is able to change the neuron spiking frequency through bidirectional signaling. This circuit may represent a fundamental computational unit for the development of artificial neuron–astrocyte networks, opening new perspectives in pattern recognition tasks.

A digital implementation of neuron–astrocyte interaction for neuromorphic applications

Recent neurophysiologic findings have shown that astrocytes play important roles in information processing and modulation of neuronal activity. Motivated by these findings, in the present research, a digital neuromorphic circuit to study neuron–astrocyte interaction is proposed. In this digital circuit, the firing dynamics of the neuron is described by Izhikevich model and the calcium dynamics of a single astrocyte is explained by a functional model introduced by Postnov and colleagues. For digital implementation of the neuron–astrocyte signaling, Single Constant Multiply (SCM) technique and several linear approximations are used for efficient low-cost hardware implementation on digital platforms. Using the proposed neuron–astrocyte circuit and based on the results of MATLAB simulations, hardware synthesis and FPGA implementation, it is demonstrated that the proposed digital astrocyte is able to change the firing patterns of the neuron through bidirectional communication. Utilizing the proposed digital circuit, it will be illustrated that information processing in synaptic clefts is strongly regulated by astrocyte. Moreover, our results suggest that the digital circuit of neuron–astrocyte crosstalk produces diverse neural responses and therefore enhances the information processing capabilities of the neuromorphic circuits. This is suitable for applications in reconfigurable neuromorphic devices which implement biologically brain circuits.