Astrocyte Ca[superscript 2+] Influx Negatively Regulates Neuronal Activity
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ENEURO.0340-16.2017.full.pdf
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Author(s)
Zhang, Yao
Ormerod, Kiel G
Littleton, J. Troy
Date Issued
March 2017
Journal
eneuro
Publisher
Society for Neuroscience
Citation
Zhang, Yao V., et al. “Astrocyte Ca[superscript 2+] Influx Negatively Regulates Neuronal Activity.” Eneuro, vol. 4, no. 2, 2017, p. ENEURO.0340-16.2017. © 2017 Zhang et al.
Version
Final published version
Abstract
Maintenance of neural circuit activity requires appropriate regulation of excitatory and inhibitory synaptic transmission. Recently, glia have emerged as key partners in the modulation of neuronal excitability; however, the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca[superscript 2+] signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca[superscript 2+] oscillatory activity manifested by fast, recurrent microdomain Ca[superscript 2+] fluctuations within processes that infiltrate the synaptic neuropil. Unlike the enhanced neuronal activity and behavioral seizures that were previously observed during manipulations that trigger Ca[superscript 2+] influx into Drosophila cortex glia, we find that acute induction of astrocyte Ca[superscript 2+] influx leads to a rapid onset of behavioral paralysis and a suppression of neuronal activity. We observe that Ca[superscript 2+] influx triggers rapid endocytosis of the GABA transporter (GAT) from astrocyte plasma membranes, suggesting that increased synaptic GABA levels contribute to the neuronal silencing and paralysis. We identify Rab11 as a novel regulator of GAT trafficking that is required for this form of activity regulation. Suppression of Rab11 function strongly offsets the reduction of neuronal activity caused by acute astrocyte Ca[superscript 2+] influx, likely by inhibiting GAT endocytosis. Our data provide new insights into astrocyte Ca[superscript 2+] signaling and indicate that distinct glial subtypes in the Drosophila brain can mediate opposing effects on neuronal excitability. Keywords: astrocyte; Ca[superscript 2+]; Drosophila; GABA; GAT; Rab11
MIT Department
Massachusetts Institute of Technology. Department of Biology
Picower Institute for Learning and Memory
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1523/ENEURO.0340-16.2017
