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(2+) signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca(2+) oscillatory activity manifested by fast, recurrent microdomain Ca(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(2+) influx into Drosophila cortex glia, we find that acute induction of astrocyte Ca(2+) influx leads to a rapid onset of behavioral paralysis and a suppression of neuronal activity. We observe that Ca(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(2+) influx, likely by inhibiting GAT endocytosis. Our data provide new insights into astrocyte Ca(2+) signaling and indicate that distinct glial subtypes in the Drosophila brain can mediate opposing effects on neuronal excitability.
