EN | FR

Cen­tre de Neu­ro­physique, Phys­i­olo­gie et Patholo­gie — CNRS UMR 8119
Uni­ver­sité Paris Descartes
45 Rue des Saints Pères
75270 Paris Cedex 06
France

Fax : +33 (0) 1 42 86 20 80

Dr. Carole LEVENES

CNRS researcher, CR-CNRS
Cere­bral Dynam­ics, Plas­tic­i­ty, Learn­ing

carole.levenes@-Code to remove to avoid SPAM-parisdescartes.fr
+33 1 42 86 41 57, room H343

Student :

Alan MONTARRAS

Technical skills :

  • Elec­tro­phys­i­ol­o­gy (extra/in­tra-cel­lu­lar record­ings, Patch-clamp in acute slices)
  • Immuno-his­to­chem­istry
  • Sin­gle-cell RT-PCR, cell cul­ture

Physiology of the cerebellum :

Devel­op­ment, synap­tic trans­mis­sion and plas­tic­i­ty
The cere­bel­lum con­tains half of the neu­rons of the brain, but lit­tle is tru­ly under­stood of its role. Tra­di­tion­al­ly, the cere­bel­lum has been con­sid­ered a struc­ture devot­ed to motor con­trol (motor coor­di­na­tion, reflex­es adap­ta­tion, motor learn­ing…). In real­i­ty though, its con­tri­bu­tion to motric­i­ty is only the most stud­ied aspect of cere­bel­lar func­tions. Recent stud­ies per­formed on Humans, show that the cere­bel­lum con­tributes sig­nif­i­cant­ly to cog­ni­tive func­tions (such as atten­tion and lan­guage) and emo­tion.

I believe that the future devel­op­ment of func­tion­al imag­ing tech­niques and in vivo record­ing pro­ce­dures will reveal that this « lit­tle brain » plays key and unex­pect­ed roles in brain func­tion.

In the mean­time, the cere­bel­lum remains an incred­i­ble mod­el for under­stand­ing neu­ronal com­mu­ni­ca­tion and the com­pu­ta­tion­al capa­bil­i­ties of neu­ronal net­works. In our group, we study synap­tic trans­mis­sion, synap­tic plas­tic­i­ty and the devel­op­ment of this amaz­ing mod­u­lar struc­ture.

Current research:

Long-term synap­tic plas­tic­i­ty is a ubiq­ui­tous neu­ronal mech­a­nism that con­trols synap­tic strength over hours and pos­si­bly days. It is like­ly to con­tribute to the estab­lish­ment of mem­o­ry for­ma­tion in the adult brain. It has also been shown to under­lie activ­i­ty-depen­dent selec­tive wiring in the imma­ture devel­op­ing brain.

In order to dis­tin­guish between these two forms of long-term synap­tic plas­tic­i­ties, we study two dis­tinct peri­ods of life in the cere­bel­lar cor­tex of mice 1) dur­ing the first week after birth and 2) in the “true adult” (i.e. after puber­ty). In these two sce­nar­ios, we look at the role of glu­ta­mate and GABA-ergic sys­tems (release/receptors) as well as the role of cel­lu­lar actors that con­tribute to the ensem­ble activ­i­ty such as the con­nex­in-like pro­teins named Pan­nex­ins.

Biomedical perspective

It is wide­ly rec­og­nized that Autism and Schiz­o­phre­nia are often asso­ci­at­ed with cere­bel­lar defects and/or abnor­mal­i­ties. We are cur­rent­ly devel­op­ing col­lab­o­ra­tions with psy­chi­a­trists to study this asso­ci­a­tion that may allow us to bet­ter under­stand the nature, and per­haps the ori­gin of these devel­op­men­tal dis­eases. In this con­text, we will study synap­tic trans­mis­sion and plas­tic­i­ty in both adults and devel­op­ing ani­mal mod­els with ear­ly cere­bel­lar lesion as well as in mod­els of Autism and Schiz­o­phre­nia.

As an exam­ple of ongo­ing work at the lab, we recent­ly made the cov­er of The Jour­nal of Neu­ro­science, Novem­ber 10, 2010 with our descrip­tion of the role of NMDA recep­tors of adult Purk­in­je cells in long-term depres­sion.

Calcium imaging in a living cerebellar Purkinje cell loaded with the calcium-sensitive dye Oregon Green BAPTA-2 in a mouse cerebellar slice.     This picture shows in false colors the projection of the resting level of fluorescence acquired by a confocal laser microscope on multiple planes of the cell. Variations of calcium intensity can be detected in spines in response to climbing fiber stimulation. This calcium signaling is partly mediated by NMDA receptors in adult rodents and plays a key role in synaptic gain control. For more information, see the article by Piochon C*. , Levenes C*., Ostuki G. and Hansel C. in The Journal of Neuroscience, November 10, 2010 • 30(45):15330 –15335.

Cal­ci­um imag­ing in a liv­ing cere­bel­lar Purk­in­je cell loaded with the cal­ci­um-sen­si­tive dye Ore­gon Green BAPTA-2 in a mouse cere­bel­lar slice.
This pic­ture shows in false col­ors the pro­jec­tion of the rest­ing lev­el of flu­o­res­cence acquired by a con­fo­cal laser micro­scope on mul­ti­ple planes of the cell. Vari­a­tions of cal­ci­um inten­si­ty can be detect­ed in spines in response to climb­ing fiber stim­u­la­tion. This cal­ci­um sig­nal­ing is part­ly medi­at­ed by NMDA recep­tors in adult rodents and plays a key role in synap­tic gain con­trol. For more infor­ma­tion, see the arti­cle by Pio­chon C*. , Lev­enes C*., Ostu­ki G. and Hansel C. in The Jour­nal of Neu­ro­science, Novem­ber 10, 2010 • 30(45):15330 –15335.

Selected publications :

Type 1 metabotrop­ic glu­ta­mate recep­tors (mGlu1) trig­ger the gat­ing of GluD2 delta glu­ta­mate recep­tors. Ady V, Per­roy J, Tri­coire L, Pio­chon C, Dadak S, Chen X, Dusart I, Fag­ni L, Lam­bolez B, Lev­enes C. 2014.
EMBO Reports 15(1), 103–109. [Abstract]  [http://embor.embopress.org/content/15/1/103.long]

Nov­el pro­tec­tive effect of mifepri­s­tone on detri­men­tal GABAA recep­tor activ­i­ty to imma­ture Purk­in­je neu­rons. Rako­toma­mon­jy J, Lev­enes C, Baulieu EE, Schu­mach­er M, Ghoumari AM. 2011. The FASEB Jour­nal 25(11), 3999–4010. [Abstract]

NMDA recep­tor con­tri­bu­tion to the climb­ing fiber response in the adult mouse Purk­in­je cell. Pio­chon C, Irinopoulou T, Brus­ciano D, Bail­ly Y, Mar­i­ani J, Lev­enes C.
J Neu­rosci. 2007 Oct 3;27(40):10797–809. [http://www.jneurosci.org/content/27/40/10797.full]

Ret­ro­grade mod­u­la­tion of trans­mit­ter release by post­sy­nap­tic sub­type 1 metabotrop­ic glu­ta­mate recep­tors in the rat cere­bel­lum. Lev­enes C, Daniel H, Cre­pel F.
J Phys­i­ol. 2001 Nov 15;537(Pt 1):125–40. [http://jp.physoc.org/content/537/1/125.long]

Cannabi­noids decrease exci­ta­to­ry synap­tic trans­mis­sion and impair long-term depres­sion in rat cere­bel­lar Purk­in­je cells. Lev­enes C, Daniel H, Soubrié P, Crépel F.
J Phys­i­ol. 1998 Aug 1;510 ( Pt 3):867–79. [http://jp.physoc.org/content/510/3/867.long]

Long-term depres­sion of synap­tic trans­mis­sion in the cere­bel­lum: cel­lu­lar and mol­e­c­u­lar mech­a­nisms revis­it­ed. Lev­enes C, Daniel H, Crépel F.
Prog Neu­ro­bi­ol. 1998 May;55(1):79–91. Review.[http://www.sciencedirect.com.gate1.inist.fr/science/article/pii/S0301008297000968]

 

Alumni:

Visou ADY (as PhD stu­dent)

Visou Ady

Present­ly post­doc  at : Dr. Alan­na J Watt’s lab, Depart­ment of Biol­o­gy, McGill Uni­ver­si­ty, Mon­tre­al Cana­da.
http://biology.mcgill.ca/faculty/watt/photos.htm

 

Frédéric JARLIER (as Research Engi­neer)

Present­ly at  : Insti­tut Curie, Paris 75005, France.

 

Visou ADY (as PhD stu­dent)

Claire Piochon

Claire PIOCHON (as PhD stu­dent in J. Mariani’s lab)

Present­ly post­doc at  : Pr. Peg­gy Mason, Dpt of Neu­ro­bi­ol­o­gy, Uni­ver­si­ty of Chica­go, Chica­go Il USA.

 

Carine MALLE (as under­grad­u­ate stu­dent, M2)

Carine Malle

Present­ly post­doc at : Insti­tut de Recherche Bio­médi­cale des Armées, France.

 

Links :

Google Schol­ar

Carole Levenes Google Scholar

LinkedIn