Contribution of astrocytes to NMDA receptor-mediated activity and plasticity

Orateur : Stéphane OLIET (Neurocentre Magendie, INSERM U1215, Bordeaux)

Astrocytes represent the major type of glial cells in the central nervous system. They are tightly associated to neurons, synapses and blood vessels. Astroglial cells are considered as the housekeepers of the brain since they ensure the clearance of toxic substance that accumulate during neuronal activity, like K+ or glutamate, and provide neurons with the appropriate energy supply and trophic factors. Beside these well-known functions, a new role has emerged for astrocytes within the last 20 years in the transfer and storage of information in the brain. Astrocytes not only detect synaptic activity through the activation of receptors located on their membrane, but also respond to it through intracellular Ca2+ signaling, thereby triggering the release of active substances that have been termed gliotransmitters by analogy to neurotransmitters. Such gliotransmitters that include glutamate, ATP and D-serine, act in a seconds to minutes time scale on neighboring neurons to modulate and/or contribute to synaptic functions and plasticity. These findings have fueled the concept of the tripartite synapse that considers astrocytes as active protagonists of information transfer between neurons. During this seminar, I would review the work carried out in my group on astroglial D-serine, an endogenous co-agonist of NMDA receptors (NMDAR). Through the supply of this D-amino acid, astrocytes regulate NMDAR activity including the most common forms of long-term synaptic plasticity in the brain. Such a regulation highlights the importance of astrocytes for physiological processes like learning and memory but also for neurodegenerative diseases and psychiatric disorders in which NMDAR have been shown to play a key role.

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