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HDR – Etienne Herzog

9 février 2016

« Vesicular glutamate transporters contribution to excitatory synapse biology in rodents. »

In the brain, neurons communicate with each other mainly through chemical synapses. Within nerve endings, classical neurotransmitters are loaded into synaptic vesicles by proton-dependent vesicular transporters before their exocytotic release. Glutamate, the major excitatory transmitter in the brain, is implicated in most neurophysiological functions. During my PhD Thesis I have contributed to the identification and characterization of three vesicular glutamate transporters (VGLUT) in the rat brain. In the present habilitation document, I draw a synthesis of the salient features of VGLUTs and explain how this contributes to our better understanding of glutamatergic neurotransmission.

This review of the literature shows the complexity of VGLUT function and raises open questions remaining to explore. 4 selected publications illustrate my recent contribution to the field using vglut1^venus and vglut1^-/- mice. Through these we contributed to the characterisation of a new pool of synaptic vesicles (named super-pool), we identified the role of VGLUT1 in the regulation of the super-pool of vesicles, questioned the presence of VGLUTs at astrocytes and paved the way toward the purification of subclasses of synaptosomes for proteomic studies. From the many perspectives to our work, I selected a few that are presented in the form of a project.

Publications récentes

Biesemann C, Grønborg M, Luquet E, Wichert SP, Bernard V, Bungers SR, Cooper B, Varoqueaux F, Li L, Byrne JA, Urlaub H, Jahn O, Brose N*, and Herzog E*. (2014) Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting The EMBO Journal, 33 : 157–170

Zhang, C.L., Houbaert, X., Lepleux, M., Deshors, M., Normand, E., Gambino, F., Herzog, E., Humeau, Y. (2014) Hippocampal projections to basolateral amygdala control contextual fear memory expression. Brain Structure and function, DOI: 10.1007/s00429-014-0882.

Houbaert X*, Zhang C-L*, Gambino F, Lepleux M, Deshors M, Normand E, Levet F, Ramos M, Billuart P, Chelly J, Herzog E & Humeau Y (2013)Target-specific vulnerability of excitatory synapses leads to deficits in associative memory in a model of intellectual disorder. The Journal of Neuroscience, 33: 13805–13819

Siksou L*, Silm K*, Biesemann C, Nehring RB, Wojcik SM, Triller A, El Mestikawy S, Marty S* & Herzog E* (2013) A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility. European Journal of Neuroscience, 37: 1631–1642

Li D,* Hérault K,* Silm K, Evrard A, Wojcik SM, Oheim M, Herzog E*, and Ropert N* (2013) Lack of Evidence for Vesicular Glutamate Transporter Expression in Mouse Astrocytes. The Journal of Neuroscience, 33: 4434-4455

Herzog E*, Nadrigny F*, Silm K*, Biesemann C, Helling I, Bersot T, Steffens H, Schwartzmann R, Nägerl UV, El Mestikawy S, Rhee JS, Kirchhoff F and Brose N. (2011) In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice. The Journal of Neuroscience, 31, 15544–15559.