title: Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures.
abstract: Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca2+ transients in astrocytes, and Ca2+ transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca2+ signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca2+ waves mediated by the release of ATP and the activation of P2 receptors. Mechanically evoked Ca2+ waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect postsynaptic glutamatergic responses but decreased presynaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca2+ waves mediated by extracellular ATP and that inhibition of these Ca2+ responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via presynaptic mechanisms.
authors.affiliation: Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. skoizumi@nihs.go.jp
authors.forename: Schuichi
authors.initials: S
authors.lastname: Koizumi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Fujishita
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuda
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shigemoto-Mogami
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D002118:Calcium