Carole Levenes Research associate (CR1) at the CNRS [1]

Technical skills:

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

Postdocs positions available

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.