Glutamate exocytosis from astrocytes controls synaptic strength.
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.
Jourdain
Pascal
P
Department of Cell Biology and Morphology, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
Bergersen
Linda H
LH
Bhaukaurally
Khaleel
K
Bezzi
Paola
P
Santello
Mirko
M
Domercq
Maria
M
Matute
Carlos
C
Tonello
Fiorella
F
Gundersen
Vidar
V
Volterra
Andrea
A
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016253:Microscopy, Immunoelectron / Q000379:methods; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D019580:Perforant Pathway / Q000502:physiology / Q000528:radiation effects; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C010739:ifenprodil