Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G. Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43: 729-743

Istituto CNR di Neuroscienze, Università di Padova, viale G. Colombo 3, 35121, Italy.
Neuron (Impact Factor: 15.05). 10/2004; 43(5):729-43. DOI: 10.1016/j.neuron.2004.08.011
Source: PubMed


Fast excitatory neurotransmission is mediated by activation of synaptic ionotropic glutamate receptors. In hippocampal slices, we report that stimulation of Schaffer collaterals evokes in CA1 neurons delayed inward currents with slow kinetics, in addition to fast excitatory postsynaptic currents. Similar slow events also occur spontaneously, can still be observed when neuronal activity and synaptic glutamate release are blocked, and are found to be mediated by glutamate released from astrocytes acting preferentially on extrasynaptic NMDA receptors. The slow currents can be triggered by stimuli that evoke Ca2+ oscillations in astrocytes, including photolysis of caged Ca2+ in single astrocytes. As revealed by paired recording and Ca2+ imaging, a striking feature of this NMDA receptor response is that it occurs synchronously in multiple CA1 neurons. Our results reveal a distinct mechanism for neuronal excitation and synchrony and highlight a functional link between astrocytic glutamate and extrasynaptic NMDA receptors.

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Available from: Olivier Pascual, Oct 04, 2015
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    • "On the other hand, single-and two-photon un-caging stimulation has been important to demonstrate the Ca2+-dependent release of gliotransmitters by astrocytes in acute brain slices (Fellin et al., 2004; Gordon et al., 2009; Liu et al., 2004; Perea and Araque, 2007) as well as permitting neuronal activation and inhibition in freely moving animals (Aravanis et al., 2007; Gradinaru et al., 2009; Wyart et al., 2009). In conjunction with spatiotemporally resolved photo-stimulation techniques, these photo-sensible tools represent the most promising alternative to electrical stimulation devices to control the activity of specific types of brain cells in time and space with sufficient precision. "
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    ABSTRACT: Present neurobiological concepts regarding superior cognitive functions are based on synaptic neurotransmission and neuronal plasticity. However, the diversity and complexity of neuro-cortical connections, circuits, maps and their relationships with memory, learning and other superior cognitive functions are not fully explained by the present neurobiological paradigms. Recent discoveries concerning the ability of neuronal cells to perceive and process very-weak electromagnetic information suggest a possible role of bio-photons generated as consequence of neuronal and astroglial metabolisms in a wide diversity of cognitive representations. Moreover, the finding that human brain has magnetite nanoparticles opens new possibilities about the role of these nano-crystals in information processing and memory. In the present chapter, a previously advanced model (Neuron-Astroglial Communication in Short-Term Memory: Bio-Electric, Bio-Magnetic and Bio-Photonic Signals?) is developed. Based in the ability of neurons and astrocytes to generate bio-photons as consequence of their metabolic activities, I propose the generation of innumerable bio-phonic-mediated nano-holograms, which are produced and modulated by magnetite nano-crystals associated to neuronal and astroglial membranes in the cerebral neocortex. Specifically, it is suggested that bio-photons generated by neuronal and astroglial cells may produce multichannel holographic pictures through their interaction with single domain and/or superparamagnetic magnetite nanoparticles, explaining retrieval of short-term and long-term memories as well as other neuro- cognitive representations such as the ―images‖ generated in dreams. Bio-chemic, bio- electric, bio-magnetic and bio-photonic activities in the cerebral cortex are not independent bio-physical phenomena, suggesting that interactions among these signals may contribute to information exchange and processing in the neocortex. This hypothesis proposes that the interactions among bio-chemic, bio-electric, bio-magnetic and bio- photonic activities in neurons and astrocytes in the human cerebral neocortex are not epiphenomena of the cerebral activity but they play important roles in cognitive functions, providing new perspectives for better understand complex cognitive functions.
    Horizons in Neuroscience Research. Volume 20, Edited by Andres Costa and Eugenio Villalba, 07/2015: chapter Holographic Memory: Magnetite Nano-Devices for Bio-Photonic Representations in the Human Brain Neocortex: pages 1-40; Nova Science Publishers., ISBN: 978-1-63482-817-8
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    • "Because a single astrocyte can contact thousands of synapses and hundreds of dendrites (Bushong et al., 2002; Halassa et al., 2007), one may hypothesize that the astrocytic networks can activate multiple neurons via the discharge of chemical transmitters. This assumption has been corroborated by experimental evidence in hippocampal slices, where astrocytic [Ca 2+ ] i rises and Ca 2+ -dependent glutamate release were described to synchronize pyramidal neurons (Angulo et al., 2004; Fellin et al., 2004; Henneberger et al., 2010; Jourdain et al., 2007). In turn, the occurrence of coordinated [Ca 2+ ] i elevations in vast astrocytic populations has been recently shown in vivo, in the visual cortex, in response to visual stimuli (Schummers et al., 2008). "
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    ABSTRACT: Recent breakthroughs in neuroscience have led to the awareness that we should revise our traditional mode of thinking and studying the CNS, i.e. by isolating the privileged network of "intelligent" synaptic contacts. We may instead need to contemplate all the variegate communications occurring between the different neural cell types, and centrally involving the astrocytes. Basically, it appears that a single astrocyte should be considered as a core that receives and integrates information from thousands of synapses, other glial cells and the blood vessels. In turn, it generates complex outputs that control the neural circuitry and coordinate it with the local microcirculation. Astrocytes thus emerge as the possible fulcrum of the functional homeostasis of the healthy CNS. Yet, evidence indicates that the bridging properties of the astrocytes can change in parallel with, or as a result of, the morphological, biochemical and functional alterations these cells undergo upon injury or disease. As a consequence, they have the potential to transform from supportive friends and interactive partners for neurons into noxious foes. In this review, we summarize the currently available knowledge on the contribution of astrocytes to the functioning of the CNS and what goes wrong in various pathological conditions, with a particular focus on amyotrophic lateral sclerosis, Alzheimer's disease and ischemia. The observations described convincingly demonstrate that the development and progression of several neurological disorders involve the de-regulation of a finely tuned interplay between multiple cell populations. Thus, it seems that a better understanding of the mechanisms governing the integrated communication and detrimental responses of the astrocytes as well as their impact towards the homeostasis and performance of the CNS is fundamental to open novel therapeutic perspectives. Copyright © 2015. Published by Elsevier Ltd.
    Progress in Neurobiology 04/2015; 29. DOI:10.1016/j.pneurobio.2015.04.003 · 9.99 Impact Factor
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    • "For example, a single gliotransmitter may exert multiple effects on the neuronal network depending on the receptor subtype and its subcellular membrane location. Indeed, glutamate released by astrocytes increases neuronal excitability by inducing slow inward currents (SICs) in excitatory neurons through activation of postsynaptic NMDA receptors (Parri et al., 2001; Angulo et al., 2004; Fellin et al., 2004; Perea and Araque, 2005; Navarrete and Araque, 2008; Shigetomi et al., 2008; Chen et al., 2012); but it also enhances synaptic transmission through activation of presynaptic metabotropic glutamate receptors (mGluRs) group I (Fiacco and McCarthy, 2004; Perea and Araque, 2007; Navarrete and Araque, 2010; Bonansco et al., 2011; Perea et al., 2014); and stimulates synaptic transmission by activation of presynaptic NMDA receptors in dentate granule cells (Jourdain et al., 2007). "
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    ABSTRACT: Astrocytes, the most abundant glial cell in the brain, play critical roles in metabolic and homeostatic functions of the Nervous System; however, their participation in coding information and cognitive processes has been largely ignored. The strategic position of astrocyte processes facing synapses and the astrocyte ability to uptake neurotransmitters and release neuroactive substances, so-called "gliotransmitters", provide the scenario for prolific neuron-astrocyte signaling. From studies at single-cell level to animal behavior, recent advances in technology and genetics have revealed the impact of astrocyte activity in brain function from cellular and synaptic physiology, neuronal circuits to behavior. The present review critically discusses the consequences of astrocyte signaling on synapses and networks, as well as its impact on neuronal information processing, showing that some crucial brain functions arise from the coordinated activity of neuron-glia networks.
    Frontiers in Cellular Neuroscience 11/2014; 8:378. DOI:10.3389/fncel.2014.00378 · 4.29 Impact Factor
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