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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

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