Astrocyte Ca[superscript 2+] Influx Negatively Regulates Neuronal Activity
Author(s)Zhang, Yao; Ormerod, Kiel G; Littleton, J. Troy
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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
DepartmentMassachusetts Institute of Technology. Department of Biology; Picower Institute for Learning and Memory
Society for Neuroscience
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.
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