dc.contributor.author | Melom, Jan Elizabeth | |
dc.contributor.author | Littleton, J. Troy | |
dc.date.accessioned | 2013-08-29T20:04:25Z | |
dc.date.available | 2013-08-29T20:04:25Z | |
dc.date.issued | 2013-01 | |
dc.date.submitted | 2012-10 | |
dc.identifier.issn | 0270-6474 | |
dc.identifier.issn | 1529-2401 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/80313 | |
dc.description.abstract | Glia 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.sponsorship | National Institutes of Health (U.S.) (NIH Grant NS43244) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (NIH grant F31NS076024) | en_US |
dc.language.iso | en_US | |
dc.publisher | Society for Neuroscience | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1523/jneurosci.3920-12.2013 | en_US |
dc.rights | Article 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.source | SFN | en_US |
dc.title | Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Melom, 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.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences | en_US |
dc.contributor.department | Picower Institute for Learning and Memory | en_US |
dc.contributor.mitauthor | Melom, Jan Elizabeth | en_US |
dc.contributor.mitauthor | Littleton, J. Troy | en_US |
dc.relation.journal | Journal of Neuroscience | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Melom, J. E.; Littleton, J. T. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-5576-2887 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |