"Inserm Avenir" Team
Development of nerve cells circuits
Contact
- Team Leader: Jean Livet (CR1, Inserm)
- E-mail: jean.livet@inserm.fr
- Phone: + 33 1 53 46 25 18
Presentation
The aim of our research is to understand how neuronal circuits of the brain are organized, how they develop and how they can be affected in diseases. We use a combination of genetic engineering and imaging to observe in situ mouse neurons and their processes (axons and dendrites) and map neuronal networks.
In particular, we have developed a new method called “Brainbow” to visualize neuronal circuits by creating a multicolor labeling of the brain. Brainbow transgenic strategies drive expression of random combinations of fluorescent proteins of distinct colors in neurons: cyan, yellow, red… (fig. 1).
Fig. 1: In Brainbow transgenic mice, nerve cells randomly express fluorescent proteins of different colors. Combinations of these proteins label neurons with multiple distinct hues, as seen here in the hippocampus (confocal microscopy, dentate gyrus).
Each neuron makes a random “choice” among a multitude of color mixtures which can be used as identity tags, as the colors which label wires in an electric circuit, (fig 2).
Fig.2: Image from a Brainbow transgenic mouse, engineered to express random combinations of cyan, yellow and red fluorescent proteins in nerve cells. As a result, neurons and their processes are labeled with a multitude of distinct hues. On this confocal microscopy image from the brain stem, tube-like structures are axons (here cross-sectioned). This image has received the 2008 Bioscape prize.
Using these hues to distinguish neurons from their neighbors, we are developing a “connectomic” reconstruction approach aiming at tracing many – or even all – neurons in a given circuit. We will use this approach to describe the cellular architecture of visual and auditory system circuits, and to study how this architecture develops.
In parallel, we are also trying to improve the Brainbow approach, and to develop new techniques to label and study neuronal circuits. The tools that we generate for neuronal circuit analysis purposes should be broadly applicable to study cellular interactions in non neuronal systems. In this line, in collaboration with other teams, we are transposing the Brainbow strategies to other cell types, in particular the oligodendrocytes which myelinate axons in the brain.
Research themes
- Reconstruction and study of neuronal circuits using Brainbow mice; characterization of cellular interactions and molecules involved in the development of neuronal circuits.
- Genetic engineering for developing new tools to visualize and study neuronal circuits.
- In collaboration with other teams, study of cellular interactions in non-neuronal cell types with Brainbow.
Last publications
Lichtman JW, Livet J, Sanes JR. A technicolour approach to the connectome. Nat Rev Neurosci (2008) 9:417-22.
Livet J. Brainbow ou le cerveau en couleurs. Med Sci. 2007 23: 1173-6.
Livet J, Weissman TA, Kang H, Draft RW, Lu J, Bennis, RA, Sanes JR, Lichtman, JW. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature, (2007) 450:56-62.
Chauvet S, Cohen S, Yoshida Y, Fekrane L, Livet J, Gayet O, Segu L, Buhot M-C, Jessell TM, Henderson CE, Mann F. Gating of Sema3E/PlexinD1 signaling by Neuropilin-1 switches axonal repulsion to attraction during brain development. Neuron, (2007) 56:807-22.
Gu C, Yoshida Y, Livet J, Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science (2005) 307:265-8.
Livet J, Sigrist M, Stroebel S, da Paolo V, Price S, Henderson CE, Jessell TM, Arber S. ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron (2002) 35:877-92.
