TY - JOUR
T1 - Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory
AU - Robin, Laurie M.
AU - Oliveira da Cruz, José F.
AU - Langlais, Valentin C.
AU - Martin-Fernandez, Mario
AU - Metna-Laurent, Mathilde
AU - Busquets-Garcia, Arnau
AU - Bellocchio, Luigi
AU - Soria-Gomez, Edgar
AU - Papouin, Thomas
AU - Varilh, Marjorie
AU - Sherwood, Mark W.
AU - Belluomo, Ilaria
AU - Balcells, Georgina
AU - Matias, Isabelle
AU - Bosier, Barbara
AU - Drago, Filippo
AU - Van Eeckhaut, Ann
AU - Smolders, Ilse
AU - Georges, Francois
AU - Araque, Alfonso
AU - Panatier, Aude
AU - Oliet, Stéphane H.R.
AU - Marsicano, Giovanni
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/6/6
Y1 - 2018/6/6
N2 - 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.
AB - 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.
KW - D-serine
KW - NMDA receptors
KW - astrocytes
KW - astroglial CB1 receptors
KW - hippocampus
KW - in vitro LTP
KW - in vivo LTP
KW - memory
KW - object recognition
KW - synapse
UR - http://www.scopus.com/inward/record.url?scp=85047214610&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2018.04.034
DO - 10.1016/j.neuron.2018.04.034
M3 - Article
C2 - 29779943
AN - SCOPUS:85047214610
SN - 0896-6273
VL - 98
SP - 935-944.e5
JO - Neuron
JF - Neuron
IS - 5
ER -