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Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation

Abstract

Astrocytes respond to chemical, electrical and mechanical stimuli with transient increases in intracellular calcium concentration ([Ca2+]i). We now show that astrocytes in situ display intrinsic [Ca2+]i oscillations that are not driven by neuronal activity. These spontaneous astrocytic oscillations can propagate as waves to neighboring astrocytes and trigger slowly decaying NMDA receptor-mediated inward currents in neurons located along the wave path. These findings show that astrocytes in situ can act as a primary source for generating neuronal activity in the mammalian central nervous system.

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Figure 1: Spontaneous astrocyte activity in the VB thalamus.
Figure 2: Effects of pharmacological agents on spontaneous [Ca2+]i transients.
Figure 3: Spontaneous [Ca2+]i transients in the VB thalamus are localized to astrocytes.
Figure 4: Propagation of spontaneous [Ca2+]i waves within and between astrocytes.
Figure 5: Localized astrocytic activity underlies signaling to neurons.
Figure 6: Astrocyte–neuron signaling is observed under physiological conditions and occurs via NMDA receptors.
Figure 7: Astrocyte–neuron signaling causes a neuronal [Ca2+]i rise.

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Acknowledgements

The authors wish to thank S.W. Hughes and T.I. Tóth for data analysis and the development of specialized statistical analysis software, and V.H. Perry for assistance with the immunocytochemistry analysis. The work was supported by the Wellcome Trust (grant 37089–98).

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Correspondence to Vincenzo Crunelli.

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Parri, H., Gould, T. & Crunelli, V. Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat Neurosci 4, 803–812 (2001). https://doi.org/10.1038/90507

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