Статья

Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures

Schuichi KoizumiDivisions of Pharmacology and Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidasi, Higashi, Fukuoka 812-8582, Japan; and Programme in Brain and Behaviour, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8Kayoko FujishitaDivisions of Pharmacology and Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidasi, Higashi, Fukuoka 812-8582, Japan; and Programme in Brain and Behaviour, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8Makoto TsudaDivisions of Pharmacology and Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidasi, Higashi, Fukuoka 812-8582, Japan; and Programme in Brain and Behaviour, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8Yukari Shigemoto‐MogamiDivisions of Pharmacology and Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidasi, Higashi, Fukuoka 812-8582, Japan; and Programme in Brain and Behaviour, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8Kazuhide InoueDivisions of Pharmacology and Biosignaling, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidasi, Higashi, Fukuoka 812-8582, Japan; and Programme in Brain and Behaviour, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8

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ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1073/pnas.1834448100

Цитирования и источники

Цитирований: 2Использованных источников: 0

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