Relevance of Exocytotic Glutamate Release from Retinal Glia

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. ► Generation of transgenic mice for inducible block of glial exocytosis ► Direct evidence for calcium-dependent vesicular glutamate release from Müller cells ► Impaired volume regulation in Müller cells after elimination of VAMP1-3 ► No effect on retinal morphology or visual processing after glial block of exocytosis Slezak et al. generate a mouse model that allows Cre- and toxin-dependent blockade of exocytosis to probe physiological roles for “gliotransmission.” Surprisingly, while exocytosis blockade in retinal glial cells impairs vesicular glutamate release and glial volume regulation, it does not affect visual function.