Increased membrane Ca<sup>2+</sup> permeability drives astrocytic Ca<sup>2+</sup> dynamics during neuronal stimulation at excitatory synapses
Hjukse, Jarand Berg; Fernández de la Puebla, Mario; Vindedal, Gry Fluge; Sprengel, Rolf; Jensen, Vidar; Nagelhus, Erlend Arnulf; Tang, Wannan
Peer reviewed, Journal article
Published version
Permanent lenke
https://hdl.handle.net/11250/3107936Utgivelsesdato
2023Metadata
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Originalversjon
10.1002/glia.24450Sammendrag
Astrocytes are intricately involved in the activity of neural circuits; however, their basic physiology of interacting with nearby neurons is not well established. Using two-photon imaging of neurons and astrocytes during higher frequency stimulation of hippocampal CA3-CA1 Schaffer collateral (Scc) excitatory synapses, we could show that increasing levels of released glutamate accelerated local astrocytic Ca2+ elevation. However, blockage of glutamate transporters did not abolish this astrocytic Ca2+ response, suggesting that astrocytic Ca2+ elevation is indirectly associated with an uptake of extracellular glutamate. However, during the astrocytic glutamate uptake, the Na+/Ca2+ exchanger (NCX) reverse mode was activated, and mediated extracellular Ca2+ entry, thereby triggering the internal release of Ca2+. In addition, extracellular Ca2+ entry via membrane P2X receptors further facilitated astrocytic Ca2+ elevation via ATP binding. These findings suggest a novel mechanism of activity induced Ca2+ permeability increases of astrocytic membranes, which drives astrocytic responses during neuronal stimulation of CA3-CA1 Scc excitatory synapses.