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

Laurie M. Robin, José F. Oliveira da Cruz, Valentin C. Langlais, Mario Martin-Fernandez, Mathilde Metna-Laurent, Arnau Busquets-Garcia, Luigi Bellocchio, Edgar Soria-Gomez, Thomas Papouin, Marjorie Varilh, Mark W. Sherwood, Ilaria Belluomo, Georgina Balcells, Isabelle Matias, Barbara Bosier, Filippo Drago, Ann Van Eeckhaut, Ilse Smolders, Francois Georges, Alfonso Araque, Aude Panatier, Stéphane H.R. Oliet, Giovanni Marsicano
Neuron. 2018-06-01; 98(5): 935-944.e5
DOI: 10.1016/j.neuron.2018.04.034

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1. Neuron. 2018 Jun 6;98(5):935-944.e5. doi: 10.1016/j.neuron.2018.04.034. Epub 2018
May 17.

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

Robin LM(1), Oliveira da Cruz JF(2), Langlais VC(1), Martin-Fernandez M(3),
Metna-Laurent M(4), Busquets-Garcia A(1), Bellocchio L(1), Soria-Gomez E(5),
Papouin T(1), Varilh M(1), Sherwood MW(1), Belluomo I(1), Balcells G(1), Matias
I(1), Bosier B(1), Drago F(6), Van Eeckhaut A(7), Smolders I(7), Georges F(8),
Araque A(3), Panatier A(1), Oliet SHR(1), Marsicano G(9).

Author information:
(1)INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of
Bordeaux, 33077 Bordeaux, France.
(2)INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of
Bordeaux, 33077 Bordeaux, France; Department of Biomedical and Biotechnological
Sciences, Section of Pharmacology, University of Catania, 95123 Catania, Italy.
(3)Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455,
USA.
(4)INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of
Bordeaux, 33077 Bordeaux, France; Aelis Farma, 33077 Bordeaux, France.
(5)INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of
Bordeaux, 33077 Bordeaux, France; Department of Neurosciences, University of the
Basque Country UPV/EHU, 48940 Leioa, Spain; IKERBASQUE, Basque Foundation for
Science, 48013 Bilbao, Spain.
(6)Department of Biomedical and Biotechnological Sciences, Section of
Pharmacology, University of Catania, 95123 Catania, Italy.
(7)Vrije Universiteit Brussel, Department of Pharmaceutical Chemistry, Drug
Analysis and Drug Information (FASC), Research group Experimental Pharmacology,
Center for Neurosciences (C4N), Laarbeeklaan 103, 1090 Brussels, Belgium.
(8)University of Bordeaux, 33077 Bordeaux, France; Centre National de la
Recherche Scientifique, Neurodegenerative Diseases Institute, UMR 5293, 33076
Bordeaux, France.
(9)INSERM U1215, NeuroCentre Magendie, 33077 Bordeaux, France; University of
Bordeaux, 33077 Bordeaux, France. Electronic address:
.

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.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuron.2018.04.034
PMID: 29779943

Auteurs Bordeaux Neurocampus