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Astrocytes are required for the oscillatory activity in cultured hippocampal neurons

Authors

  • Claudia Verderio,

    1. CNR Cellular and Molecular Pharmacology and ‘B. Ceccarelli’ Centers, Department of Medical Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
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  • Alberto Bacci,

    1. CNR Cellular and Molecular Pharmacology and ‘B. Ceccarelli’ Centers, Department of Medical Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
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  • Silvia Coco,

    1. CNR Cellular and Molecular Pharmacology and ‘B. Ceccarelli’ Centers, Department of Medical Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
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  • Elena Pravettoni,

    1. CNR Cellular and Molecular Pharmacology and ‘B. Ceccarelli’ Centers, Department of Medical Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
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  • Guido Fumagalli,

    1. Institute of Pharmacology, University of Verona, Italy
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  • Michela Matteoli

    1. CNR Cellular and Molecular Pharmacology and ‘B. Ceccarelli’ Centers, Department of Medical Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
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: Dr Michela Matteoli, as above.
E-mail: MichelaM@Farma.csfic.mi.cnr.it

Abstract

Synchronous oscillations of intracellular calcium concentration ([Ca2+]i) and of membrane potential occurred in a limited population of glutamatergic hippocampal neurons grown in primary cultures. The oscillatory activity occurred in synaptically connected cells only when they were in the presence of astrocytes. Microcultures containing only one or a few neurons also displayed oscillatory activity, provided that glial cells participated in the network. The glutamate-transporter inhibitors L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) and dihydrokainate, which produce an accumulation of glutamate in the synaptic microenvironment, impaired the oscillatory activity. Moreover, in neurons not spontaneously oscillating, though in the presence of astrocytes, oscillations were induced by exogenous l-glutamate, but not by the stereoisomer d-glutamate, which is not taken up by glutamate transporters. These data demonstrate that astrocytes are essential for neuronal oscillatory activity and provide evidence that removal of glutamate from the synaptic environment is one of the major mechanisms by which glial cells allow the repetitive excitation of the postsynaptic cell.

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