Key Points
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Over the past two decades, our understanding of the role of brain glial cells, in particular astrocytes, has fundamentally changed. Indeed, dynamic interactions between astrocytes, neurons and the vasculature have been in the spotlight of neuroscience.
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It has emerged that not only neurons but also astrocytes are organized into networks and communicate through specialized intercellular channels made by connexins, the so-called gap junction channels. Therefore, neuroglial and gliovascular interactions should also be considered at a multicellular and more integrated level — that is, beyond a dialogue between single cells.
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The widespread expression of connexins and the extensive intercellular communication between astrocytes initially led to the notion that astrocytes were organized as a syncytium. However, accumulating evidence shows that astrocytes form networks of communicating cells that, like neurons, are governed by rules.
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In specific brain regions that are characterized by a compartmentalized organization of functional neuronal units, the communication between astrocytes is favoured within these compartments.
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Gap junction communication is controlled by endogenous compounds, including neurotransmitters, and is therefore dependent on neuronal activity defining a certain degree of plasticity.
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The existence of astroglial networks may extend neuroglial dialogue by allowing information processing and integration by a large number of neurons. Also, astroglial networks might have a role in providing energetic metabolites to remote sites during high neuronal demand.
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Changes in the expression of astroglial connexins have been reported in diverse pathological situations that may also affect the extent and shape of astroglial networks. However, it remains unknown whether these changes are the cause or the consequence of neuronal dysfunction and death.
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In the future, new pharmacological and genetic approaches will be required to understand how and why the expression and function of astroglial connexin channels are controlled. Identification of the molecules that can permeate through gap junction channels is another important challenge that must be overcome to fully understand the physiology of astrocyte networks. Indeed, the level of connexin expression is unique and certainly has a crucial role in the contribution of astrocytes to brain metabolism and processing.
Abstract
Dynamic aspects of interactions between astrocytes, neurons and the vasculature have recently been in the neuroscience spotlight. It has emerged that not only neurons but also astrocytes are organized into networks. Whereas neuronal networks exchange information through electrical and chemical synapses, astrocytes are interconnected through gap junction channels that are regulated by extra- and intracellular signals and allow exchange of information. This intercellular communication between glia has implications for neuroglial and gliovascular interactions and hence has added another level of complexity to our understanding of brain function.
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Acknowledgements
The authors wish to thank C. Genoud and E. Welker (University of Lausanne) for providing EM illustrations and J. Glowinski (Collège de France, Paris) for his support and interest for our work.
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Supplementary information
Supplementary information S1 (table)
Changes in Cx expression associated with pathological situations in the central nervous sytem (PDF 311 kb)
Supplementary information S2 (table)
Consequences of Cx molecular block on neuronal activity or survival in pathological situations (PDF 223 kb)
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Glossary
- Tripartite synapse
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A concept in synaptic physiology based on the existence of communication between the pre- and postsynaptic terminal and a surrounding astrocyte.
- Neurovascular coupling
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The link between neuronal activity and energy supply from blood flow, in which astrocytes participate.
- Astrocyte–neuron lactate shuttle
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Activity-dependent fuelling of neuronal energy demand, consisting of glucose uptake at astrocyte endfeet, its glycolysis and the delivery of lactate to neurons by astrocytes.
- Reactive astrocytes
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Astroglia that, after brain injuries or during pathology, are characterized by functional and morphological changes that can be associated with cell migration and proliferation.
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Giaume, C., Koulakoff, A., Roux, L. et al. Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat Rev Neurosci 11, 87–99 (2010). https://doi.org/10.1038/nrn2757
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DOI: https://doi.org/10.1038/nrn2757
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