In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice

The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many synapses in the mammalian brain. Due to its function and selective localization, VGLUT1 is one of the most specific markers for glutamatergic synapt...

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Published in:The Journal of neuroscience Vol. 31; no. 43; pp. 15544 - 15559
Main Authors: Herzog, Etienne, Nadrigny, Fabien, Silm, Katlin, Biesemann, Christoph, Helling, Imke, Bersot, Tiphaine, Steffens, Heinz, Schwartzmann, Richard, Nägerl, U. Valentin, El Mestikawy, Salah, Rhee, JeongSeop, Kirchhoff, Frank, Brose, Nils
Format: Journal Article
Language:English
Published: Society for Neuroscience 26-10-2011
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Abstract The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many synapses in the mammalian brain. Due to its function and selective localization, VGLUT1 is one of the most specific markers for glutamatergic synaptic vesicles. It has been used widely to identify glutamatergic synapses, and its expression levels are tightly correlated with changes in quantal size, modulations of synaptic plasticity, and corresponding behaviors. We generated a fluorescent VGLUT1 Venus knock-in mouse for the analysis of VGLUT1 and glutamatergic synaptic vesicle trafficking. The mutation does not affect glutamatergic synapse function, and thus the new mouse model represents a universal tool for the analysis of glutamatergic transmitter systems in the forebrain. Previous studies demonstrated synaptic vesicle exchange between terminals in vitro . Using the VGLUT1 Venus knock-in, we show that synaptic vesicles are dynamically shared among boutons in the cortex of mice in vivo . We provide a detailed analysis of synaptic vesicle sharing in vitro , and show that network homeostasis leads to dynamic scaling of synaptic VGLUT1 levels.
AbstractList The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many synapses in the mammalian brain. Due to its function and selective localization, VGLUT1 is one of the most specific markers for glutamatergic synaptic vesicles. It has been used widely to identify glutamatergic synapses, and its expression levels are tightly correlated with changes in quantal size, modulations of synaptic plasticity, and corresponding behaviors. We generated a fluorescent VGLUT1 Venus knock-in mouse for the analysis of VGLUT1 and glutamatergic synaptic vesicle trafficking. The mutation does not affect glutamatergic synapse function, and thus the new mouse model represents a universal tool for the analysis of glutamatergic transmitter systems in the forebrain. Previous studies demonstrated synaptic vesicle exchange between terminals in vitro . Using the VGLUT1 Venus knock-in, we show that synaptic vesicles are dynamically shared among boutons in the cortex of mice in vivo . We provide a detailed analysis of synaptic vesicle sharing in vitro , and show that network homeostasis leads to dynamic scaling of synaptic VGLUT1 levels.
Author Helling, Imke
Nadrigny, Fabien
Herzog, Etienne
Biesemann, Christoph
Steffens, Heinz
Nägerl, U. Valentin
Kirchhoff, Frank
Schwartzmann, Richard
El Mestikawy, Salah
Silm, Katlin
Rhee, JeongSeop
Brose, Nils
Bersot, Tiphaine
Author_xml – sequence: 1
  givenname: Etienne
  surname: Herzog
  fullname: Herzog, Etienne
  organization: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany, Institut National de la Santé et de la Recherche Médicale, U952, 75005 Paris, France, Centre National de la Recherche Scientifique (CNRS) UMR 7224, 75005 Paris, France, Université Pierre et Marie Curie (UPMC), Pathophysiology of Central Nervous System Disorders, 75005 Paris, France
– sequence: 2
  givenname: Fabien
  surname: Nadrigny
  fullname: Nadrigny, Fabien
  organization: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany, Université de Bordeaux, 33076 Bordeaux, France, CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33076 Bordeaux, France
– sequence: 3
  givenname: Katlin
  surname: Silm
  fullname: Silm, Katlin
  organization: Institut National de la Santé et de la Recherche Médicale, U952, 75005 Paris, France, Centre National de la Recherche Scientifique (CNRS) UMR 7224, 75005 Paris, France, Université Pierre et Marie Curie (UPMC), Pathophysiology of Central Nervous System Disorders, 75005 Paris, France
– sequence: 4
  givenname: Christoph
  surname: Biesemann
  fullname: Biesemann, Christoph
  organization: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
– sequence: 5
  givenname: Imke
  surname: Helling
  fullname: Helling, Imke
  organization: Department of Cellular and Systems Neurobiology, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany
– sequence: 6
  givenname: Tiphaine
  surname: Bersot
  fullname: Bersot, Tiphaine
  organization: Institut National de la Santé et de la Recherche Médicale, U952, 75005 Paris, France, Centre National de la Recherche Scientifique (CNRS) UMR 7224, 75005 Paris, France, Université Pierre et Marie Curie (UPMC), Pathophysiology of Central Nervous System Disorders, 75005 Paris, France
– sequence: 7
  givenname: Heinz
  surname: Steffens
  fullname: Steffens, Heinz
  organization: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany, Institute of Physiology, Georg August University of Göttingen, 37073 Göttingen, Germany, and Department of NanoBiophotonics, Max Planck Institute of Biophysical Chemistry, 37077 Göttingen, Germany
– sequence: 8
  givenname: Richard
  surname: Schwartzmann
  fullname: Schwartzmann, Richard
  organization: UPMC, Service d'Imagerie Cellulaire et Cytométrie en Flux, IFR83, 75005 Paris, France
– sequence: 9
  givenname: U. Valentin
  surname: Nägerl
  fullname: Nägerl, U. Valentin
  organization: Université de Bordeaux, 33076 Bordeaux, France, CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33076 Bordeaux, France, Department of Cellular and Systems Neurobiology, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany
– sequence: 10
  givenname: Salah
  surname: El Mestikawy
  fullname: El Mestikawy, Salah
  organization: Institut National de la Santé et de la Recherche Médicale, U952, 75005 Paris, France, Centre National de la Recherche Scientifique (CNRS) UMR 7224, 75005 Paris, France, Université Pierre et Marie Curie (UPMC), Pathophysiology of Central Nervous System Disorders, 75005 Paris, France
– sequence: 11
  givenname: JeongSeop
  surname: Rhee
  fullname: Rhee, JeongSeop
  organization: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
– sequence: 12
  givenname: Frank
  surname: Kirchhoff
  fullname: Kirchhoff, Frank
  organization: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany, Department of Physiology, University of Saarland, D-66421 Homburg, Germany
– sequence: 13
  givenname: Nils
  surname: Brose
  fullname: Brose, Nils
  organization: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
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Notes Author contributions: E.H., F.N., U.V.N., S.E.M., JS.R., and N.B. designed research; E.H., F.N., K.S., C.B., I.H., T.B., H.S., R.S., U.V.N., and JS.R. performed research; F.K. and N.B. contributed unpublished reagents/analytic tools; E.H., F.N., K.S., C.B., I.H., T.B., U.V.N., S.E.M., JS.R., and N.B. analyzed data; E.H. and N.B. wrote the paper.
E.H., F.N., and K.S. contributed equally to this work.
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Snippet The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many...
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Title In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice
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