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Etienne Herzog " Learning from VGLUT1venus knock-in mice: watching boutons & sorting synapses. "

Abstract :


The neurotransmitter glutamate is loaded show approximately 70 % sequence identity and were found to possess virtually identical bioenergetics and pharmacology of neurotransmitter loading.
However, VGLUT1-3 display differential expression patterns throughout development and at adult stages and therefore define three glutamatergic systems, that may display differences in synaptic physiology and pathology. VGLUT1 is essentially used in cortical regions implicated in complex cognitive functions, which mature during post-natal development. VGLUT2 is expressed from early developmental stages, in deeper brain regions responsible for sensory motor functions as well as autonomic regulatory processes. Together, VGLUT1 and VGLUT2 mark all classical glutamatergic neurons.
In this context, tracking VGLUT specific synapses and identifying their functional specializations is at the center of our interest. To that end we developed a VGLUT1venus fluorescent knock in mouse. In this mouse model the VGLUT1venus protein is expressed in place of the wild type VGLUT1. The expression patterns and trafficking features of the chimera are extremely similar if not identical to the WT VGLUT1 protein.
We now take advantage of these mice to image VGLUT1 specific neurons and synapses in-vitro as well as in-vivo. Finally we are establishing a synaptosome purification approach using Fluorescence Activated Cell Sorting.

Selected publications

Herzog E., Takamori S., Jahn R., Brose N & Wojcik S.
Synaptic and Vesicular Co-localization of the Glutamate Transporters VGLUT1 and VGLUT2 in the Mouse Hippocampus.Journal of Neurochemistry, 2006 Nov;99(3):1011-8.

Vinatier J, Herzog E, Plamont MA, Wojcik SM, Schmidt A, Brose N, Daviet L, El Mestikawy S, Giros B.
Interaction between the vesicular glutamate transporter type 1 and endophilin A1, a protein essential for endocytosis. Journal of Neurochemistry, 2006 May;97(4):1111-25.

Wojcik S.M. *, Rhee J.S. *, Herzog E., Sigler A., Jahn R., Takamori S., Brose N., and Rosenmund C.
An essential role for VGLUT1 in postnatal development and control of quantal size.Proc. Natl. Acad. Sci. U.S.A., 2004, vol 101(18), 7158-7163.

Françoise Coussen