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Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission

  • QING-SONG LIU (a1), QIWU XU (a1), JIAN KANG (a1) and MAIKEN NEDERGAARD (a1)

Abstract

In the CNS, fine processes of astrocytes often wrap around dendrites, axons and synapses, which provides an interface where neurons and astrocytes might interact. We have reported previously that selective Ca2+ elevation in astrocytes, by photolysis of caged Ca2+ by o-nitrophenyl-EGTA (NP-EGTA), causes a kainite receptor-dependent increase in the frequency of spontaneous inhibitory post-synaptic potentials (sIPSCs) in neighboring interneurons in hippocampal slices. However, tetrodotoxin (TTX), which blocks action potentials, reduces the frequency of miniature IPSCs (mIPSCs) in interneurons during Ca2+ uncaging by an unknown presynaptic mechanism. In this study we investigate the mechanism underlying the presynaptic inhibition. We show that Ca2+ uncaging in astrocytes is accompanied by a decrease in the amplitude of evoked IPSCs (eIPSCs) in neighboring interneurons. The decreases in eIPSC amplitude and mIPSC frequency are prevented by CPPG, a group II/III metabotropic glutamate receptor (mGluR) antagonist, but not by the AMPA/kainate and NMDA receptor antagonists CNQX/CPP. Application of either the group II mGluR agonist DCG IV or the group III mGluR agonist L-AP4 decreased the amplitude of eIPSCs by a presynaptic mechanism, and both effects are blocked by CPPG. Thus, activation of mGluRs mediates the effects of Ca2+ uncaging on mIPSCs and eIPSCs. Our results indicate that Ca2+-dependent release of glutamate from astrocytes can activate distinct classes of glutamate receptors and differentially modulate inhibitory synaptic transmission in hippocampal interneurons.

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Corresponding author

Dr. Maiken Nedergaard, Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, KMRB1.9915 Rochester, New York 14642, USA. phone: +1 585 2732868; fax: +1 585 2735561. email: nedergaard@urmc.rochester.edu

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Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission

  • QING-SONG LIU (a1), QIWU XU (a1), JIAN KANG (a1) and MAIKEN NEDERGAARD (a1)

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