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      Neuron-glia networks: integral gear of brain function

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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.

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          Most cited references63

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          Tripartite synapses: glia, the unacknowledged partner.

          According to the classical view of the nervous system, the numerically superior glial cells have inferior roles in that they provide an ideal environment for neuronal-cell function. However, there is a wave of new information suggesting that glia are intimately involved in the active control of neuronal activity and synaptic neurotransmission. Recent evidence shows that glia respond to neuronal activity with an elevation of their internal Ca2+ concentration, which triggers the release of chemical transmitters from glia themselves and, in turn, causes feedback regulation of neuronal activity and synaptic strength. In view of these new insights, this article suggests that perisynaptic Schwann cells and synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses.
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            The role of acetylcholine in learning and memory.

            Pharmacological data clearly indicate that both muscarinic and nicotinic acetylcholine receptors have a role in the encoding of new memories. Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within these regions. Acetylcholine has been shown to increase the strength of afferent input relative to feedback, to contribute to theta rhythm oscillations, activate intrinsic mechanisms for persistent spiking, and increase the modification of synapses. These effects might enhance different types of encoding in different cortical structures. In particular, the effects in entorhinal and perirhinal cortex and hippocampus might be important for encoding new episodic memories.
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              Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior.

              Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity, and coordinates firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here, we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss consequences of this signaling on behaviors related to drug abuse, attention, food intake, and affect. The diverse effects of acetylcholine depend on site of release, receptor subtypes, and target neuronal population; however, a common theme is that acetylcholine potentiates behaviors that are adaptive to environmental stimuli and decreases responses to ongoing stimuli that do not require immediate action. The ability of acetylcholine to coordinate the response of neuronal networks in many brain areas makes cholinergic modulation an essential mechanism underlying complex behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                28 September 2014
                06 November 2014
                2014
                : 8
                : 378
                Affiliations
                [1] 1Functional and System Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas Madrid, Spain
                [2] 2Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology Cambridge, MA, USA
                [3] 3Department of Neuroscience, University of Minnesota, Minneapolis MN, USA
                Author notes

                Edited by: Vladimir Parpura, University of Alabama, USA

                Reviewed by: Dmitri A. Rusakov, University College London, UK; Jean-pierre Mothet, CNRS - Aix Marseille University, France

                *Correspondence: Gertrudis Perea, Functional and System Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Av. Doctor Arce, 37, Madrid 28002, Spain e-mail: gperea@ 123456cajal.csic.es ; Alfonso Araque, Department Neuroscience, University of Minnesota, 4-110 Wallin Medical Biosciences Building, 2101 6th Street, Minneapolis, 55455 MN, USA e-mail: araque@ 123456umn.edu

                This article was submitted to the journal Frontiers in Cellular Neuroscience.

                Article
                10.3389/fncel.2014.00378
                4222327
                25414643
                03d07330-ca35-47fd-a166-7055ea88daac
                Copyright © 2014 Perea, Sur and Araque.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 September 2014
                : 22 October 2014
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 93, Pages: 8, Words: 6673
                Categories
                Neuroscience
                Review Article

                Neurosciences
                astrocytes,neuron-glia network,synaptic plasticity,gliotransmission,information coding

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