Article abstract
Nature Neuroscience 10, 331 - 339 (2007)
Published online: 18 February 2007 | doi:10.1038/nn1849
Glutamate exocytosis from astrocytes controls synaptic strength
Pascal Jourdain1,6, Linda H Bergersen2,6, Khaleel Bhaukaurally1,6, Paola Bezzi1, Mirko Santello1, Maria Domercq3, Carlos Matute3, Fiorella Tonello4, Vidar Gundersen2,5 & Andrea Volterra1
Abstract
The release of transmitters from glia influences synaptic functions. The modalities and physiological functions of glial release are poorly understood. Here we show that glutamate exocytosis from astrocytes of the rat hippocampal dentate molecular layer enhances synaptic strength at excitatory synapses between perforant path afferents and granule cells. The effect is mediated by ifenprodil-sensitive NMDA ionotropic glutamate receptors and involves an increase of transmitter release at the synapse. Correspondingly, we identify NMDA receptor 2B subunits on the extrasynaptic portion of excitatory nerve terminals. The receptor distribution is spatially related to glutamate-containing synaptic-like microvesicles in the apposed astrocytic processes. This glial regulatory pathway is endogenously activated by neuronal activity–dependent stimulation of purinergic P2Y1 receptors on the astrocytes. Thus, we provide the first combined functional and ultrastructural evidence for a physiological control of synaptic activity via exocytosis of glutamate from astrocytes.
- Department of Cell Biology and Morphology, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
- Department of Anatomy and the Centre of Molecular Biology and Neuroscience, University of Oslo, POB 1105 Blindern, 0317 Oslo, Norway.
- Department of Neurosciences, University of the Basque Country, 48640 Leioa, Vizcaya, Spain.
- Department of Biomedical Sciences, University of Padova, Viale Colombo, 3, 35121 Padova, Italy.
- Department of Neurology, Rikshospitalet University Hospital, 0023 Oslo, Norway.
- These authors contributed equally to this work.
Correspondence to: Andrea Volterra1 e-mail: andrea.volterra@unil.ch
Correspondence to: Vidar Gundersen2,5 e-mail: vidar.gundersen@medisin.uio.no
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