Insights into the release mechanism of astrocytic glutamate evoking in neurons NMDA receptor-mediated slow depolarizing inward currents

Glia
Marta Gomez-GonzaloGiorgio Carmignoto

Abstract

The gliotransmitter glutamate in different brain regions modulates neuronal excitability and synaptic transmission through a variety of mechanisms. Among the hallmarks of astrocytic glutamate release are the slow depolarizing inward currents (SICs) in neurons mediated by N-methyl-d-aspartate receptor activation. Different stimuli that evoke Ca2+ elevations in astrocytes induce neuronal SICs suggesting a Ca2+ -dependent exocytotic glutamate release mechanism of SIC generation. To gain new insights into this mechanism, we investigated the relationship between astrocytic Ca2+ elevations and neuronal SICs in mouse hippocampal slice preparations. Here we provide evidence that SICs, occurring either spontaneously or following a hypotonic challenge, are unchanged in the virtual absence of Ca2+ signal changes at astrocytic soma and processes, including spatially restricted Ca2+ microdomains. SICs are also unchanged in the presence of Bafilomycin A1 that after prolonged slice incubation depletes glutamate from astrocytic vesicles. We also found that hemichannels and TREK family channels-that recent studies proposed to mediate astrocytic glutamate release - are not involved in SIC generation. SICs are reduced by the volume-sensitive anio...Continue Reading

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Citations

Mar 3, 2019·International Journal of Molecular Sciences·Eiji ShigetomiSchuichi Koizumi
Dec 17, 2020·International Journal of Molecular Sciences·Daniele LanaMaria Grazia Giovannini
Apr 9, 2021·Frontiers in Neurology·Oscar B AlcorezaHarald Sontheimer
Jun 25, 2021·Frontiers in Cellular Neuroscience·Annamaria LiaGabriele Losi

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