Journal
NEURON
Volume 98, Issue 5, Pages 935-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2018.04.034
Keywords
-
Categories
Funding
- INSERM
- CNRS
- EU-Fp7 [HEALTH-603191]
- European Research Council [ERC-2010-StG-260515, ERC-2014-PoC-640923]
- Fondation pour la Recherche Modicale [DRM20101220445, DPP20151033974, FDT20160435664, DEQ 20130326519, FDT20150532252]
- Human Frontiers Science Program [RGP0036//2014]
- Region Aquitaine
- Agence Nationale de la Recherche (ANR Blanc NeuroNutriSens) [ANR-13-BSV4-0006, ANR-10-LABX-0043]
- Fyssen Foundation
- CONACyT
- EMBO post-doc fellowship
- FRM post-doc fellowship
- French Ministry of Higher Education and Research
Ask authors/readers for more resources
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 CA(3)CA(1) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available