Normal and pathological glutamatergic systems

Research center

9 Quai Saint-Bernard Université Pierre et Marie Curie, Campus Jussieu, Bâtiments A-B-C
75005 Paris
Michel Labouesse

Institution

Inserm
CNRS
Université Pierre et Marie Curie

Laboratory

Neuroscience Paris Seine
U1130 UMR8246 UMCR18

Mots clefs

brain
neurotransmission
Glutamate
Neurological psychiatric diseases
Vesicular glutamate transporter
Available to host a PhD student

publications

Siksou L., Silm K., Biesemann C., Nehring R.B., Wojcik S.M., Triller A., El Mestikawy S., Marty S. and Herzog, E. European J Neuroscience 12199. (2013)

El Mestikawy et al.From glutamate co-release to vesicular synergy: vesicular glutamate transporters.Nat Rev Neurosci. 2011 Apr;12(4): pp. 204-16

Herzog et al.In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice J Neurosci. (2011) Oct 26;31(43):15544-59

Bernard V. et al.Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction.Mol. Cell. Neurosci. 46: (2011); pp. 272-281

Dobbertin A. … et Bernard V. Targeting of Acetylcholinesterase in Neurons: a Dual Function for PRiMA and its AChE Recognition Domain in vivo. J. Neurosci. 29: (2009); pp. 4519 –4530.

Amilhon et al. VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of serotonergic transmission and anxiety J Neurosci (2010) 30: pp. 2198-210.

Fields of research

Neurophysiology / systems neuroscience

Research Theme

Glutamate is the major neurotransmitter of CNS. Before its exocytotic release in the synaptic cleft, glutamate is loaded into synaptic vesicles by three transporters named VGLUT1-3. In the rodent brain, VGLUT1-3 are distributed in three complementary glutamatergic systems showing little overlap. VGLUT1 is essentially cortical, VGLUT2 subcortical and VGLUT3 is present in neurons using other transmitters than glutamate (cholinergic interneurons from the striatum, GABAergic interneurons from the hippocampus and cortex and serotonergic neurons). The three VGLUTs are the first available specific markers of glutamatergic neurons and terminals. These proton-dependent carriers share a high degree of structural and functional homology.

The strength of synaptic transmission is controlled both at the pre- and post-synaptic levels. Vesicular glutamate transporters play an essential role in glutamatergic transmission. Indeed, recent studies have documented that the concentration of vesicular transporters directly impacts on the strength of synaptic transmission.

Lab rotation

Regulation of reward circuit and addiction by cholinergic interneurons of the nucleus accumbens

Chercheur responsable: 

ELMESTIKAWVY Salah

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

The striatum regulates motor control, habits, goal directed behaviors and reward behaviors. Striatal dysfunction underlies several diseases such as Parkinson disease, obsessive-compulsive disorder and addiction. Cholinergic interneurons are major modulators of striatal function. These neurons store and release two classical neurotransmitters: ACh and glutamate (Glu). The proposed project will investigate the implication of cholinergic interneurons and co-transmission in the normal and pathological striatum.

We will focus on reward  (relevant for addiction) and goal-directed behavior or habits (relevant for obsessive compulsive disorders or feeding behaviors). The project will combine mouse model and human studies (post-mortem, genetic). Technically the entire project will involve: anatomy, biochemistry, optogenetic, behavior and electrophysiology. The rotation will include: i) mutant mouse characterization, ii) in vivo electrophysiological recording and iii) human genetic. In vivo Electrophysiology will be done in collaboration with Philippe Faure Team and Human Genetic with the team of Stéphane Jamain.


Contact

Neuroscience Paris Seine - Bât B 4ème étage, pièce 418 - 9 quai Saint Bernard, case courrier 37, 75252 Paris cedex 05 - +33 1 44 27 61 23

Superviseur: 

ELMESTIKAWVY Salah & JAMAIN Stéphane