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Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo

Nature Neuroscience volume 9, pages 816–823 (2006)Cite this article

Abstract

Although astrocytes are the most abundant cell type in the brain, evidence for their activation during physiological sensory activity is lacking. Here we show that whisker stimulation evokes increases in astrocytic cytosolic calcium (Ca2+) within the barrel cortex of adult mice. Increases in astrocytic Ca2+ were a function of the frequency of stimulation, occurred within several seconds and were inhibited by metabotropic glutamate receptor antagonists. To distinguish between synaptic input and output, local synaptic activity in cortical layer 2 was silenced by iontophoresis of AMPA and NMDA receptor antagonists. The antagonists did not reduce astrocytic Ca2+ responses despite a marked reduction in excitatory postsynaptic currents in response to whisker stimulation. These findings indicate that astrocytes respond to synaptic input, by means of spillover or ectopic release of glutamate, and that increases in astrocytic Ca2+ occur independently of postsynaptic excitatory activity.

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Figure 1: Whisker stimulation evokes astrocytic Ca2+ increases in barrel cortex.
Figure 2: Temporal relationship between LFP signals and increases in astrocytic Ca2+ in response to whisker stimulation.
Figure 3: Astrocytic responses to whisker stimulation do not require activation of postsynaptic AMPA and NMDA receptors.
Figure 4: Increases in astrocytic Ca2+ in response to whisker stimulation are mediated by mGluRs.
Figure 5: Dependence of astrocytic Ca2+ responses on frequency of whisker stimulation.

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Acknowledgements

We thank S. Goldman, K. Kasischke, E. Vates, L. Bekar and N. Oberheim for their comments on the manuscript and D. Pinto for discussion. This work was supported in part by grants NS30007 and NS38073 from the US National Institutes of Health and the National Institute of Neurological Disorders and Stroke (to M.N.) and the Phillip Morris External Research Program.

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Authors and Affiliations

  1. Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, 14642, New York, USA

    Xiaohai Wang, Nanhong Lou, Qiwu Xu, Guo-Feng Tian, Wei Guo Peng, Xiaoning Han, Takahiro Takano & Maiken Nedergaard

  2. Department of Cell Biology and Anatomy, New York Medical College, 30 Sunshine Cottage Road, Valhalla, 10595, New York, USA

    Jian Kang

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Supplementary information

Supplementary Fig. 1

Spontaneous astrocytic Ca2+ activity in anesthetized mice. (PDF 414 kb)

Supplementary Fig. 2

The frequency of astrocytic Ca2+ oscillations was artificially increased with increased 2-photon laser power. (PDF 455 kb)

Supplementary Fig. 3

Astrocytic Ca2+ responses to whisker stimulation are not modulated by 2-photon excitation when laser power is low. (PDF 502 kb)

Supplementary Fig. 4

1 Hz whisker stimulation failed to induce astrocytic Ca2+ increase. (PDF 287 kb)

Supplementary Video 1

Z step imaging of adult FVB mouse loaded with fluo-4/am. (MOV 1913 kb)

Supplementary Video 2

Spontaneous astrocytic Ca2+ signaling in barrel cortex layer 2. (MOV 2393 kb)

Supplementary Video 3

Whisker stimulation repeatedly triggered astrocytic Ca2+ increases in barrel cortex layer 2. (MOV 2386 kb)

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Wang, X., Lou, N., Xu, Q. et al. Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo. Nat Neurosci 9, 816–823 (2006). https://doi.org/10.1038/nn1703

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