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 AraqueAude Panatier, Stéphane H.R. Oliet, Giovanni Marsicano

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


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. Robin et al. show that astroglial CB1 receptors in the hippocampus regulate D-serine supply to NMDA receptors, a process necessary for LTP induction and object recognition memory.

Original languageEnglish
Pages (from-to)935-944.e5
Issue number5
StatePublished - Jun 6 2018


  • D-serine
  • NMDA receptors
  • astrocytes
  • astroglial CB1 receptors
  • hippocampus
  • in vitro LTP
  • in vivo LTP
  • memory
  • object recognition
  • synapse


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