caa a22 4500 606203176 CHVBK 20210128100956.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00429-014-0829-2 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0829-2 Genetic ablation of VIAAT in glycinergic neurons causes a severe respiratory phenotype and perinatal death [Elektronische Daten] [Jamilur Rahman, Stefanie Besser, Christian Schnell, Volker Eulenburg, Johannes Hirrlinger, Sonja Wojcik, Swen Hülsmann] Both glycinergic and GABAergic neurons require the vesicular inhibitory amino acid transporter (VIAAT) for synaptic vesicle filling. Presynaptic GABA concentrations are determined by the GABA-synthesizing enzymes glutamate decarboxylase (GAD)65 and GAD67, whereas the presynaptic glycine content depends on the plasma membrane glycine transporter 2 (GlyT2). Although severely impaired, glycinergic transmission is not completely absent in GlyT2-knockout mice, suggesting that other routes of glycine uptake or de novo synthesis of glycine exist in presynaptic terminals. To investigate the consequences of a complete loss of glycinergic transmission, we generated a mouse line with a conditional ablation of VIAAT in glycinergic neurons by crossing mice with loxP-flanked VIAAT alleles with a GlyT2-Cre transgenic mouse line. Interestingly, conditional VIAAT knockout (VIAAT cKO) mice were not viable at birth. In addition to the dominant respiratory failure, VIAAT cKO showed an umbilical hernia and a cleft palate. Immunohistochemistry revealed an almost complete depletion of VIAAT in the brainstem. Electrophysiology revealed the absence of both spontaneous glycinergic and GABAergic inhibitory postsynaptic currents from hypoglossal motoneurons. Our results demonstrate that the deletion of VIAAT in GlyT2-Cre expressing neurons also strongly affects GABAergic transmission and suggest a large overlap of the glycinergic and the GABAergic neuron population during early development in the caudal parts of the brain. Springer-Verlag Berlin Heidelberg, 2014 Embryonic development nationallicence Transmitter release nationallicence Vesicular filling nationallicence Electrophysiology nationallicence Brainstem nationallicence Rahman Jamilur Institute for Neurophysiology and Cellular Biophysics, Georg-August-University Göttingen, Humboldtallee 23, 37073, Göttingen, Germany aut Besser Stefanie Carl-Ludwig-Institute for Physiology, University of Leipzig, Liebigstrasse 27, 04103, Leipzig, Germany aut Schnell Christian Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany aut Eulenburg Volker Institute for Biochemistry and Molecular Medicine, University of Erlangen, Fahrstrasse 17, 91054, Erlangen, Germany aut Hirrlinger Johannes Carl-Ludwig-Institute for Physiology, University of Leipzig, Liebigstrasse 27, 04103, Leipzig, Germany aut Wojcik Sonja Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075, Göttingen, Germany aut Hülsmann Swen Clinic for Anesthesiology, Laboratory for Experimental Neuroanesthesiology, University Hospital Göttingen, Humboldtallee 23, 37073, Göttingen, Germany aut Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 2835-2849 1863-2653 220:5<2835 2015 220 429 https://doi.org/10.1007/s00429-014-0829-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0829-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rahman Jamilur Institute for Neurophysiology and Cellular Biophysics, Georg-August-University Göttingen, Humboldtallee 23, 37073, Göttingen, Germany aut NATIONALLICENCE 700 1- Besser Stefanie Carl-Ludwig-Institute for Physiology, University of Leipzig, Liebigstrasse 27, 04103, Leipzig, Germany aut NATIONALLICENCE 700 1- Schnell Christian Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany aut NATIONALLICENCE 700 1- Eulenburg Volker Institute for Biochemistry and Molecular Medicine, University of Erlangen, Fahrstrasse 17, 91054, Erlangen, Germany aut NATIONALLICENCE 700 1- Hirrlinger Johannes Carl-Ludwig-Institute for Physiology, University of Leipzig, Liebigstrasse 27, 04103, Leipzig, Germany aut NATIONALLICENCE 700 1- Wojcik Sonja Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075, Göttingen, Germany aut NATIONALLICENCE 700 1- Hülsmann Swen Clinic for Anesthesiology, Laboratory for Experimental Neuroanesthesiology, University Hospital Göttingen, Humboldtallee 23, 37073, Göttingen, Germany aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 2835-2849 1863-2653 220:5<2835 2015 220 429