Vesicular glutamate transporters in cognition – VGLUT-IQ

Our project is based on the use of a custom made mouse model expressing fluorescence at a large population of excitatory synapses (see: www.inb.u- bordeaux2.fr/siteneuro2/pages/archiindex/Herzog/glutamate.php).
To better understand the rôle of intersynaptic sharing of synaptic vesicles we use a combination of genetics, optic and electrophysiologic approaches.
To characterize the synaptic proteome in physiology and pathology, we use a novel method allowing to purify synapses that are fluorescent.

Our first results in this project, allow us to identify the role of vesicular glutamate transporters in the regulation of synaptic vesicle sharing among terminals of a same neuron.
To know more see: www.neuroscience.univ- bordeauxsegalen.fr/en/miscellaneous/interviews/etienne-herzog.html

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A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility. Léa Siksou, Kätlin Silm, Christoph Biesemann, Ralf B. Nehring, Sonja M. Wojcik, Antoine Triller, Salah El Mestikawy, Serge Marty, and Etienne Herzog.
European Journal of Neuroscience, 37, 10, p1631–1642, May 2013

VGLUT-IQ project is developed in continuity of a decade of research of Etienne Herzog in the field of excitatory pre-synapses using glutamate as their main neurotransmitter. Vesicular GLUtamate Transporters represent the main molecular markers of glutamatergic presynapses. Their main function is to translocate glutamate from the cytoplasm into synaptic vesicles (SV) thereby contributing significantly to the pace of neurotransmission. VGLUTs are therefore a subject of research per se and important tools to gain knowledge on excitatory synapse formation, maintenance and physiology.
As a focus, VGLUTs are currently the subject of investigations for additional functions secondary to the main transport of glutamate. VGLUT-IQ proposes to unravel possible interesting molecular properties of VGLUT1 and possibly -2 and -3 in SV mobility at synapses.
Concomitantly, our goal is to understand the effect of inter-synaptic SV mobility on neurotransmission and synapse plasticity in physiological and mental retardation conditions. Our physiological model to study synapse plasticity is the VGLUT1 cortical projection to lateral amygdala dissected in acute slices. To reach specificity we will benefit from the use of our recently published VGLUT1venus fluorescent mouse line.
Our last ambition is to provide a comparative synaptic proteome of the VGLUT1 type of excitatory synapses from lateral amygdala between Wild type and Il1rapl1 deficient mice, an “archetypal” mouse model of non-syndromic mental retardation. To that end we developed the most advanced to date purification of synaptic particles (synaptosomes) from central tissue (Biesemann et al., under review, see appendix).
Altogether thanks to the ANR funding of VGLUT-IQ, we will provide major datasets on excitatory presynaptic function and plasticity at the cortico-lateral amygdala connection in physiology and intellectual disability.