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Glia

From kiss-and-run to crosstalk

Astrocytes can respond to neuronal activity and actively modulate neurotransmission by releasing glial transmitters such as glutamate, ATP and D-serine. Two recent studies have taken important steps in understanding the mechanisms of glial transmitter release and the role of gliotransmission in regulating synaptic strength and plasticity.

The calcium-dependent vesicular release of gliotransmitters in response to membrane receptor activation is thought to depend on SNARE proteins, but many questions remain about the mode of gliotransmitter exocytosis.

Chen et al. used electrochemical amperometry and frequency-modulated (fluorescent) single-vesicle imaging to look at the kinetics of stimulus-evoked vesicular release from cultured and freshly isolated rat hippocampal astrocytes. In response to strong, non-physiological stimulation, astrocytes adopted a permanent fusion mode, in which most of the vesicle contents were secreted. As expected, stimulus-induced quantal secretion was SNARE dependent in these glial cells. To their surprise, the researchers found that physiological stimulation caused astrocytes to release their contents by a kiss-and-run mechanism, in which only 10% of the vesicle contents were released during a brief opening of the 'fusion pore' — a channel that connects and spans the vesicle and plasma membranes. In neurons, the fusion pore can switch on and off many times in a process known as 'flickering'; however, kiss-and-run in astrocytes appeared to involve just a single 'kiss' or 'flicker'.

Pascual and colleagues exploited the SNARE dependence of glial transmitter release to investigate the role of gliotransmission in synaptic networks. To block gliotransmitter release, the researchers generated transgenic mice that expressed a dominant-negative (dn)SNARE domain in astrocytes. They studied synaptic transmission and long-term potentiation (LTP) in acutely isolated hippocampal slices from these animals. By releasing ATP, which is rapidly hydrolysed to adenosine, Pascual et al. found that astrocytes can tonically suppress excitatory synaptic transmission by activating A1 adenosine receptors. And by regulating the strength of basal synaptic transmission, it seems that these glial cells can enhance the available range for synaptic plasticity, the magnitude of LTP being significantly reduced in dnSNARE mice. Because ATP can diffuse to distant sites before adenosine begins to accumulate, the synaptic activation of astrocytes provides a mechanism for crosstalk to distant synapses.

These studies add to a burgeoning literature on the active roles of astrocytes in synaptic networks. It will be interesting to learn whether differences in the characteristics of kiss-and-run exocytosis in neurons and glia are related to differences in the fusion proteins expressed by these cell types. We look forward with interest to the next steps in our understanding of the regulatory functions of astrocytes in synaptic transmission.

References

ORIGINAL RESEARCH PAPERS

  1. Chen, X. et al. “Kiss-and-run” glutamate secretion in cultured and freshly isolated rat hippocampal astrocytes. J. Neurosci. 25, 9236–9243 (2005)

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  2. Pascual, O. et al. Astrocytic purinergic signalling coordinates synaptic networks. Science 310, 113–116 (2005)

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FURTHER READING

  1. Volterra, A. & Meldolesi, J. Astrocytes, from brain glue to communication elements: the revolution continues. Nature Rev. Neurosci. 6, 626–640 (2005)

    CAS  Article  Google Scholar 

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Craven, R. From kiss-and-run to crosstalk. Nat Rev Neurosci 6, 914 (2005). https://doi.org/10.1038/nrn1815

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  • DOI: https://doi.org/10.1038/nrn1815

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