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, although the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca2+ signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca2+ oscillatory activity manifested by fast, recurrent microdomain Ca2+ fluctuations within processes that infiltrate the synaptic neuropil. Unlike the enhanced neuronal activity and behavioral seizures that were previously observed during manipulations that trigger Ca2+ influx into Drosophila cortex glia, we find that acute induction of astrocyte Ca2+ influx leads to a rapid onset of behavioral paralysis and a suppression of neuronal activity. We observe that Ca2+ influx triggers rapid endocytosis of the γ-amino butyric acid (GABA) transporter (GAT) from astrocyte plasma membranes, suggesting 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 Ca2+ influx, likely by inhibiting GAT endocytosis. Our data provide new insights into astrocyte Ca2+ signaling and indicate that distinct glial subtypes in the Drosophila brain can mediate opposing effects on neuronal excitability.
Significance Statement Complex brain functions require precise control of neuronal activity, which is often disrupted in neurologic disorders such as epilepsy. Here we show that Drosophila astrocytes exhibit endogenous spontaneous Ca2+ oscillatory activity. Acute elevation of astrocyte Ca2+ suppresses neuronal activity and causes rapid paralysis. This is accompanied by a rapid reduction in the levels of membrane GAT, a transporter for the inhibitory neurotransmitter GABA. We identify Rab11 as a novel regulator of GAT trafficking that is required for this form of Ca2+-dependent astrocyte regulation of neuronal activity. Our study provides new insight into the acute regulation of neuronal activity by glia.
Authors report no conflict of interest.
This work was supported by HHS/NIH grant NS40296.