2026-09-20T07:57:22Zhttps://dspace.mit.edu/server/oai/request

oai:dspace.mit.edu:1721.1/791602022-01-13T07:53:55Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022

J. Troy Littleton. Melom, Jan E. (Jan Elizabeth) Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology 2013-06-17T19:04:17Z 2013-06-17T19:04:17Z 2013 2013 http://hdl.handle.net/1721.1/79160 844348732 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013. This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. Cataloged from student-submitted PDF version of thesis. Includes bibliographical references. Glial cells exhibit spontaneous and activity-dependent fluctuations in intracellular Ca²+, yet it is unclear whether glial Ca²+ oscillations are required during neuronal signaling. Somatic glial Ca²+ waves are primarily mediated by the release of intracellular Ca²+ stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca²+ 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 Ca²+ oscillations in Drosophila cortex glia of the central nervous system. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na+/Ca²+, K+ exchanger (zydeco) that is required for microdomain Ca²+ oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to several environmental stressors, 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 Ca²+/calmodulin-dependent glial signaling pathway is involved in acute glial-neuronal communication. These studies demonstrate that microdomain glial Ca²+ oscillations require NCKX-mediated plasma membrane Ca²+ flux, and are essential for normal neuronal excitability. by Jan E. Melom. Ph.D. 160 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Biology. Microdomain calcium oscillations in Drosophila glia regulate seizure susceptibility and require NCKX Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="b2db85ff-17c4-4c67-80b2-e8c8b5f34d16"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Microdomain calcium oscillations in Drosophila glia regulate seizure susceptibility and require NCKX</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2013</PublicationDate> <Authors> <Author> <DisplayName>Melom, Jan E. (Jan Elizabeth)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <Abstract>Glial cells exhibit spontaneous and activity-dependent fluctuations in intracellular Ca²+, yet it is unclear whether glial Ca²+ oscillations are required during neuronal signaling. Somatic glial Ca²+ waves are primarily mediated by the release of intracellular Ca²+ stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca²+ 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 Ca²+ oscillations in Drosophila cortex glia of the central nervous system. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na+/Ca²+, K+ exchanger (zydeco) that is required for microdomain Ca²+ oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to several environmental stressors, 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 Ca²+/calmodulin-dependent glial signaling pathway is involved in acute glial-neuronal communication. These studies demonstrate that microdomain glial Ca²+ oscillations require NCKX-mediated plasma membrane Ca²+ flux, and are essential for normal neuronal excitability.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>