Emery Lab – Current Biology Publication

Emery Lab – Current Biology Publication

Link- https://www.cell.com/current-biology/pdfExtended/S0960-9822(22)00336-0

Sleep is indispensable for normal brain function and overall health. Glia and neurons interact to control sleep and wake, but how glia exerts its influence on sleep is not yet well understood. Ratna Chaturvedi from the Emery Lab at UMass Chan Medical School and her collaborators at the Vollum Center (OHSU) recently published their findings in Current Biology showing that the astrocytic GABA transporter GAT controls sleep by regulating GABA tone on wake-promoting circadian neurons in Drosophila. Their work thus reveals a novel and important molecular mechanism that modulates sleep in fruit flies.

Authors Summary:

A precise balance between sleep and wakefulness is essential to sustain a good quality of life and optimal brain function. GABA is known to play a key and conserved role in sleep control, and GABAergic tone should, therefore, be tightly controlled in sleep circuits. Here, we examined the role of the astrocytic GABA trans- porter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat33-1) increased sleep amount, decreased sleep latency, and increased sleep consolidation at night. Interestingly, sleep defects were suppressed when gat33-1 was combined with a mutation disrupting wide- awake (wake), a gene that regulates the cell-surface levels of the GABAA receptor resistance to dieldrin (RDL) in the wake-promoting large ventral lateral neurons (l-LNvs). Moreover, RNAi knockdown of rdl and its modulators dnlg4 and wake in these circadian neurons also suppressed gat33-1 sleep phenotypes. Brain immunohistochemistry showed that GAT-expressing astrocytes were located near RDL-positive l-LNv cell bodies and dendritic processes. We concluded that astrocytic GAT decreases GABAergic tone and RDL activation in arousal- promoting LNvs, thus determining proper sleep amount and quality in Drosophila.