Computational Astrocyence: Astrocytes encode inhibitory activity into the frequency and spatial extent of their calcium elevations

Deciphering the complex interactions between neurotransmission and astrocytic $Ca^{2+}$ elevations is a target promising a comprehensive understanding of brain function. While the astrocytic response to excitatory synaptic activity has been extensively studied, how inhibitory activity results to intracellular $Ca^{2+}$ waves remains elusive. In this study, we developed a compartmental astrocytic model that exhibits distinct levels of responsiveness to inhibitory activity. Our model suggested that the astrocytic coverage of inhibitory terminals defines the spatial and temporal scale of their $Ca^{2+}$ elevations. Understanding the interplay between the synaptic pathways and the astrocytic responses will help us identify how astrocytes work independently and cooperatively with neurons, in health and disease.Comment: 4 pages, 3 figures, IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI '19

A Neural-Astrocytic Network Architecture: Astrocytic calcium waves modulate synchronous neuronal activity

Understanding the role of astrocytes in brain computation is a nascent challenge, promising immense rewards, in terms of new neurobiological knowledge that can be translated into artificial intelligence. In our ongoing effort to identify principles endow-ing the astrocyte with unique functions in brain computation, and translate them into neural-astrocytic networks (NANs), we propose a biophysically realistic model of an astrocyte that preserves the experimentally observed spatial allocation of its distinct subcellular compartments. We show how our model may encode, and modu-late, the extent of synchronous neural activity via calcium waves that propagate intracellularly across the astrocytic compartments. This relationship between neural activity and astrocytic calcium waves has long been speculated but it is still lacking a mechanistic explanation. Our model suggests an astrocytic "calcium cascade" mechanism for neuronal synchronization, which may empower NANs by imposing periodic neural modulation known to reduce coding errors. By expanding our notions of information processing in astrocytes, our work aims to solidify a computational role for non-neuronal cells and incorporate them into artificial networks.Comment: International Conference on Neuromorphic Systems (ICONS) 201

Introducing Astrocytes on a Neuromorphic Processor: Synchronization, Local Plasticity and Edge of Chaos

While there is still a lot to learn about astrocytes and their neuromodulatory role in the spatial and temporal integration of neuronal activity, their introduction to neuromorphic hardware is timely, facilitating their computational exploration in basic science questions as well as their exploitation in real-world applications. Here, we present an astrocytic module that enables the development of a spiking Neuronal-Astrocytic Network (SNAN) into Intel's Loihi neuromorphic chip. The basis of the Loihi module is an end-to-end biophysically plausible compartmental model of an astrocyte that simulates the intracellular activity in response to the synaptic activity in space and time. To demonstrate the functional role of astrocytes in SNAN, we describe how an astrocyte may sense and induce activity-dependent neuronal synchronization, switch on and off spike-time-dependent plasticity (STDP) to introduce single-shot learning, and monitor the transition between ordered and chaotic activity at the synaptic space. Our module may serve as an extension for neuromorphic hardware, by either replicating or exploring the distinct computational roles that astrocytes have in forming biological intelligence.Comment: 9 pages, 7 figure

A roadmap to integrate astrocytes into Systems Neuroscience.

Systems neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well-documented homeostatic and metabolic functions, perform computations implementing mathematical algorithms that sub-serve coding and higher-brain functions. First, we reviewed Systems-like studies that include astrocytes in order to identify computational operations that these cells may perform, using Ca2+ transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in a time scale of subseconds to seconds in sensory processing, neuromodulation, brain state, memory formation, fear, and complex homeostatic reflexes. Next, we propose a list of actions to gain insight into the outstanding question of which variables are encoded by such computations. The application of statistical analyses based on machine learning, such as dimensionality reduction and decoding in the context of complex behaviors, combined with connectomics of astrocyte-neuronal circuits, is, in our view, fundamental undertakings. We also discuss technical and analytical approaches to study neuronal and astrocytic populations simultaneously, and the inclusion of astrocytes in advanced modeling of neural circuits, as well as in theories currently under exploration such as predictive coding and energy-efficient coding. Clarifying the relationship between astrocytic Ca2+ and brain coding may represent a leap forward toward novel approaches in the study of astrocytes in health and disease

A roadmap to integrate astrocytes into Systems Neuroscience

Systems Neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well-documented homeostatic and metabolic functions, perform computations implementing mathematical algorithms that sub-serve coding and higher-brain functions. First, we reviewed Systems-like studies that include astrocytes in order to identify computational operations that these cells may perform, using Ca$^{2+}$ transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in time scales of sub-seconds to seconds in sensory processing, neuromodulation, brain state, memory formation, fear, and complex homeostatic reflexes. Next, we propose a list of actions to gain insight into the outstanding question of which variables are encoded by such computations. The application of statistical analyses based on machine learning, such as dimensionality reduction and decoding in the context of complex behaviors, combined with connectomics of astrocyte-neuronal circuits, are, in our view, fundamental undertakings. We also discuss technical and analytical approaches to study neuronal and astrocytic populations simultaneously, and the inclusion of astrocytes in advanced modeling of neural circuits, as well as in theories currently under exploration, such as predictive coding and energy-efficient coding. Clarifying the relationship between astrocytic Ca$^{2+}$ and brain coding may represent a leap forward towards novel approaches in the study of astrocytes in health and disease.Junior Leader Fellowhip Program by 'la Caixa' Banking Foundation, LCF/BQ/LI18/11630006 BFU2017-85936-P BFU2016-75107-P BFU2016-79735-P FLAGERA-PCIN-2015-162-C02-02 HHMI 55008742 FPU13/05377 NIH R01NS099254 NSF 1604544 Agència de Gestio d’Ajuts Universitaris i de Recerca, 2017 SGR54

The hemo-neural hypothesis : effects of vasodilation on astrocytes in mammalian neocortex

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011.Cataloged from PDF version of thesis.Includes bibliographical references.Astrocytes play an important role in regulating neuronal activity and local brain states, in part by serving as intermediaries between neurons and vasculature. We postulate that neurons and astrocytes are sensitive to biophysical conditions in their local environment, in addition to their participation in traditional signaling networks with other neurons. Mechanically sensitive astrocytic endfeet ensheathe cerebral blood vessels, which change size in order to regulate blood flow. We found that changes in local biophysical state caused by mechanical perturbations exerted through blood vessels can depolarize astrocytes and some neurons in slice. To test the hemoneural hypothesis in vivo, we developed a means of inducing dilation using the SUR2B receptor agonist pinacidil, which is specific to vascular smooth muscle. It was important to ascertain that pinacidil had no direct effect on astrocytes or neurons, and we confirmed this in whole cell recordings in cortical slices. We then used two-photon imaging to visualize astrocytic calcium dynamics in vivo while manipulating vasodilation in vivo. Pinacidil caused a 10-20% dilation in most vessels, a degree of dilation of similar magnitude to those naturally evoked by persistent sensory stimulation (e.g. in fMRI studies). We found that increases in pial arteriole diameter could occasionally evoke traveling calcium waves in astrocytes. We also saw consistently slow increases (which took tens of seconds to onset, and persisted for minutes) in astrocytic calcium levels at both endfeet and soma in cortical layer 1, corresponding to vessel dilation. When vessels partially reconstricted due to pinacidil washout, calcium levels also showed a relative decrease. At short time scales (from 0.5 - 5 seconds) we saw strong correlations (>0.5) between small fluctuations in astrocytic calcium levels (1-3%) and vessel diameter (1-3%). Fluctuations in vessel diameter predicted similar fluctuations in astrocytic calcium, as often and as strongly as the reverse, suggesting feedback regulation between vascular diameter and astrocytic calcium activation levels.by Rosa Cao.Ph.D

Deep Artificial Neural Networks and Neuromorphic Chips for Big Data Analysis: Pharmaceutical and Bioinformatics Applications

[Abstract] Over the past decade, Deep Artificial Neural Networks (DNNs) have become the state-of-the-art algorithms in Machine Learning (ML), speech recognition, computer vision, natural language processing and many other tasks. This was made possible by the advancement in Big Data, Deep Learning (DL) and drastically increased chip processing abilities, especially general-purpose graphical processing units (GPGPUs). All this has created a growing interest in making the most of the potential offered by DNNs in almost every field. An overview of the main architectures of DNNs, and their usefulness in Pharmacology and Bioinformatics are presented in this work. The featured applications are: drug design, virtual screening (VS), Quantitative Structure–Activity Relationship (QSAR) research, protein structure prediction and genomics (and other omics) data mining. The future need of neuromorphic hardware for DNNs is also discussed, and the two most advanced chips are reviewed: IBM TrueNorth and SpiNNaker. In addition, this review points out the importance of considering not only neurons, as DNNs and neuromorphic chips should also include glial cells, given the proven importance of astrocytes, a type of glial cell which contributes to information processing in the brain. The Deep Artificial Neuron–Astrocyte Networks (DANAN) could overcome the difficulties in architecture design, learning process and scalability of the current ML methods.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