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dc.contributor.authorMelom, Jan Elizabeth
dc.contributor.authorLittleton, J. Troy
dc.date.accessioned2013-08-29T20:04:25Z
dc.date.available2013-08-29T20:04:25Z
dc.date.issued2013-01
dc.date.submitted2012-10
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.urihttp://hdl.handle.net/1721.1/80313
dc.description.abstractGlia exhibit spontaneous and activity-dependent fluctuations in intracellular Ca[superscript 2+], yet it is unclear whether glial Ca[superscript 2+] oscillations are required during neuronal signaling. Somatic glial Ca[superscript 2+] waves are primarily mediated by the release of intracellular Ca[superscript 2+] stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca[superscript 2+] transients were identified in fine astrocytic processes and found to arise via an intracellular store-independent process. Here, we describe the identification of rapid, near-membrane Ca[superscript 2+] oscillations in Drosophila cortex glia of the CNS. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na[superscript +]/Ca[superscript 2+], K[superscript +] exchanger (zydeco) that is required for microdomain Ca[superscript 2+] oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to a variety of environmental stimuli, and that zydeco is required acutely in cortex glia to regulate seizure susceptibility. We also found that glial expression of calmodulin is required for stress-induced seizures in zydeco mutants, suggesting a Ca[superscript 2+]/calmodulin-dependent glial signaling pathway underlies glial–neuronal communication. These studies demonstrate that microdomain glial Ca[superscript 2+] oscillations require NCKX-mediated plasma membrane Ca[superscript 2+] flux, and that acute dysregulation of glial Ca[superscript 2+] signaling triggers seizures.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant NS43244)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant F31NS076024)en_US
dc.language.isoen_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1523/jneurosci.3920-12.2013en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceSFNen_US
dc.titleMutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibilityen_US
dc.typeArticleen_US
dc.identifier.citationMelom, J. E., and J. T. Littleton. “Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility.” Journal of Neuroscience 33, no. 3 (January 16, 2013): 1169-1178.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorMelom, Jan Elizabethen_US
dc.contributor.mitauthorLittleton, J. Troyen_US
dc.relation.journalJournal of Neuroscienceen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsMelom, J. E.; Littleton, J. T.en_US
dc.identifier.orcidhttps://orcid.org/0000-0001-5576-2887
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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