title: Relevance of exocytotic glutamate release from retinal glia.
abstract: Glial cells release molecules that influence brain development, function, and disease. Calcium-dependent exocytosis has been proposed as potential release mechanism in astroglia, but the physiological relevance of "gliotransmission" in vivo remains controversial. We focused on the impact of glial exocytosis on sensory transduction in the retina. To this end, we generated transgenic mice to block exocytosis by Cre recombinase-dependent expression of the clostridial botulinum neurotoxin serotype B light chain, which cleaves vesicle-associated membrane protein 1-3. Ubiquitous and neuronal toxin expression caused perinatal lethality and a reduction of synaptic transmission thus validating transgene function. Toxin expression in Müller cells inhibited vesicular glutamate release and impaired glial volume regulation but left retinal histology and visual processing unaffected. Our model to study gliotransmission in vivo reveals specific functions of exocytotic glutamate release in retinal glia.
authors.affiliation: CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences, 67084 Strasbourg, France.
authors.forename: Michal
authors.initials: M
authors.lastname: Slezak
authors.forename: Antje
authors.initials: A
authors.lastname: Grosche
authors.forename: Aurore
authors.initials: A
authors.lastname: Niemiec
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Münch
authors.forename: Britni
authors.initials: B
authors.lastname: Crocker
authors.forename: Philippe
authors.initials: P
authors.lastname: Isope
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Beck
authors.forename: Gesine
authors.initials: G
authors.lastname: Huber
authors.forename: Geraldine
authors.initials: G
authors.lastname: Ferracci
authors.forename: Martine
authors.initials: M
authors.lastname: Perraut
authors.forename: Michael
authors.initials: M
authors.lastname: Reber
authors.forename: Monique
authors.initials: M
authors.lastname: Miehe
authors.forename: Valérie
authors.initials: V
authors.lastname: Demais
authors.forename: Christian
authors.initials: C
authors.lastname: Lévêque
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Klaudia
authors.initials: K
authors.lastname: Szklarczyk
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Dominique
authors.initials: D
authors.lastname: Sage-Ciocca
authors.forename: Johannes
authors.initials: J
authors.lastname: Hirrlinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Sophie
authors.initials: S
authors.lastname: Reibel
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001905:Botulinum Toxins / Q000235:genetics / Q000378:metabolism; D019274:Botulinum Toxins, Type A; D002232:Carbocyanines / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008027:Light; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009457:Neuroglia / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D019887:Peanut Agglutinin / Q000378:metabolism; D010775:Photic Stimulation; D011930:Reaction Time / Q000235:genetics; D012160:Retina / Q000166:cytology*; D018709:Statistics, Nonparametric; D013629:Tamoxifen / Q000494:pharmacology; D041623:Tomography, Optical Coherence; D014466:Ultraviolet Rays; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: C020932:11-cis-retinal-binding protein; D002232:Carbocyanines; D002352:Carrier Proteins; D004965:Estrogen Antagonists; D019887:Peanut Agglutinin; C098830:TO-PRO-3; D050988:Vesicle-Associated Membrane Protein 2; D050598:Vesicular Glutamate Transport Protein 1; C485184:enhanced green fluorescent protein; D013629:Tamoxifen; C096323:rimabotulinumtoxinB; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; C045073:Cre recombinase; D019426:Integrases; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A