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The Journal of Neuroscience, September 1, 1998, 18(17):6822-6829
Calcium Elevation in Astrocytes Causes an NMDA Receptor-Dependent
Increase in the Frequency of Miniature Synaptic Currents in Cultured
Hippocampal Neurons
Alfonso
Araque,
Rita P.
Sanzgiri,
Vladimir
Parpura, and
Philip G.
Haydon
Laboratory of Cellular Signaling, Department of Zoology and
Genetics, Iowa State University, Ames, Iowa 50011
Astrocytes exhibit a form of excitability and communication on the
basis of intracellular Ca2+ variations (; ) that can be initiated by neuronal
activity (; ). A
Ca2+ elevation in astrocytes induces the release of
glutamate (; ; ; ), which evokes a slow inward current in
neurons and modulates action potential-evoked synaptic transmission
between cultured hippocampal cells (), suggesting
that astrocytes and neurons may function as a network with
bidirectional communication. Here we show that a
Ca2+ elevation in astrocytes increases the frequency
of excitatory as well as inhibitory miniature postsynaptic currents
(mPSCs), without modifying their amplitudes. Thapsigargin incubation,
microinjection of the Ca2+ chelator BAPTA, and
photolysis of the Ca2+ cage NP-EGTA demonstrate that
a Ca2+ elevation in astrocytes is both necessary and
sufficient to modulate spontaneous transmitter release. This
Ca2+-dependent release of glutamate from astrocytes
enhances mPSC frequency by acting on NMDA glutamate receptors,
because it is antagonized by D-2-amino-5-phosphonopentanoic
acid (AP5) or extracellular Mg2+. These NMDA
receptors are located extrasynaptically, because blockage specifically
of synaptic NMDA receptors by synaptic activation in the presence of
the open channel blocker MK-801 did not impair the AP5-sensitive
astrocyte-induced increase of mPSC frequency. Therefore, astrocytes
modulate spontaneous excitatory and inhibitory synaptic transmission by
increasing the probability of transmitter release via the activation of
NMDA receptors.
Key words:
astrocyte-neuron signaling; NMDA glutamate receptors; calcium cage photolysis; calcium waves; miniature synaptic currents; hippocampal synaptic transmission
Copyright © 1998 Society for Neuroscience 0270-6474/98/18176822-08$05.00/0
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