Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors.
Fast excitatory neurotransmission is mediated by activation of synaptic ionotropic glutamate receptors. In hippocampal slices, we report that stimulation of Schaffer collaterals evokes in CA1 neurons delayed inward currents with slow kinetics, in addition to fast excitatory postsynaptic currents. Similar slow events also occur spontaneously, can still be observed when neuronal activity and synaptic glutamate release are blocked, and are found to be mediated by glutamate released from astrocytes acting preferentially on extrasynaptic NMDA receptors. The slow currents can be triggered by stimuli that evoke Ca2+ oscillations in astrocytes, including photolysis of caged Ca2+ in single astrocytes. As revealed by paired recording and Ca2+ imaging, a striking feature of this NMDA receptor response is that it occurs synchronously in multiple CA1 neurons. Our results reveal a distinct mechanism for neuronal excitation and synchrony and highlight a functional link between astrocytic glutamate and extrasynaptic NMDA receptors.
Fellin
Tommaso
T
Istituto CNR di Neuroscienze, Università di Padova, viale G. Colombo 3, 35121, Italy.
Pascual
Olivier
O
Gobbo
Sara
S
Pozzan
Tullio
T
Haydon
Philip G
PG
Carmignoto
Giorgio
G
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D003344:Cortical Synchronization; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid