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Article Dans Une Revue Neuron Année : 2018

Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory

Arnau Busquets-Garcia
Ann van Eeckhaut
  • Fonction : Auteur
Ilse Smolders
  • Fonction : Auteur
Alfonso Araque
Aude Panatier
Stéphane H.R. Oliet
Giovanni Marsicano

Résumé

Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB1 receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB1 receptors from astroglial cells (GFAP-CB1-KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses. Activation of CB1 receptors increased intracellular astroglial Ca2+ levels and extracellular levels of D-serine in hippocampal slices. Accordingly, GFAP-CB1-KO displayed lower occupancy of the co-agonist binding site of synaptic hippocampal NMDARs. Finally, elevation of D-serine levels fully rescued LTP and memory impairments of GFAP-CB1-KO mice. These data reveal a novel mechanism of in vivo astroglial control of memory and synaptic plasticity via the D-serine-dependent control of NMDARs.

Domaines

Neurobiologie
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Dates et versions

hal-03139015 , version 1 (16-02-2021)

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Laurie M Robin, José F Oliveira da Cruz, Valentin C Langlais, Mario Martin-Fernandez, Mathilde Metna-Laurent, et al.. Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory. Neuron, 2018, 98 (5), pp.935 - 944.e5. ⟨10.1016/j.neuron.2018.04.034⟩. ⟨hal-03139015⟩

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