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dc.contributor.authorChaturvedi, Ratna
dc.contributor.authorStork, Tobias
dc.contributor.authorYuan, Chunyan
dc.contributor.authorFreeman, Marc R.
dc.contributor.authorEmery, Patrick
dc.date2022-08-11T08:08:34.000
dc.date.accessioned2022-08-23T15:59:40Z
dc.date.available2022-08-23T15:59:40Z
dc.date.issued2022-03-17
dc.date.submitted2022-05-05
dc.identifier.citation<p>Chaturvedi R, Stork T, Yuan C, Freeman MR, Emery P. Astrocytic GABA transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons. Curr Biol. 2022 Mar 14:S0960-9822(22)00336-0. doi: 10.1016/j.cub.2022.02.066. Epub ahead of print. PMID: 35303417. <a href="https://doi.org/10.1016/j.cub.2022.02.066">Link to article on publisher's site</a></p>
dc.identifier.issn0960-9822 (Linking)
dc.identifier.doi10.1016/j.cub.2022.02.066
dc.identifier.pmid35303417
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30722
dc.description.abstractA 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 transporter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat(33-1)) increased sleep amount, decreased sleep latency, and increased sleep consolidation at night. Interestingly, sleep defects were suppressed when gat(33-1) 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 gat(33-1) 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=35303417&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.cub.2022.02.066
dc.subjectGABA
dc.subjectGAT
dc.subjectastrocytes
dc.subjectlarge ventral lateral neurons
dc.subjectsleep
dc.subjectNeuroscience and Neurobiology
dc.titleAstrocytic GABA transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons
dc.typeArticle
dc.source.journaltitleCurrent biology : CB
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2193
dc.identifier.contextkey29018200
html.description.abstract<p>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 transporter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat(33-1)) increased sleep amount, decreased sleep latency, and increased sleep consolidation at night. Interestingly, sleep defects were suppressed when gat(33-1) 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 gat(33-1) 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.</p>
dc.identifier.submissionpathfaculty_pubs/2193
dc.contributor.departmentEmery Lab
dc.contributor.departmentDepartment of Neurobiology
dc.contributor.departmentFreeman Lab


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