The mature nervous system is an intricate network in which neurons are connected to specific partners. The choice of these partners is crucial for the correct behavior of the network (meaning the nervous system) and is determined at early stages of development. Abnormal development of neuronal connections is responsible for a large range of neuronal pathologies, some of them affecting vision. Research carried on by our team focuses on a better understanding of the development of sensory maps including the connection between the retina and the brain.
We aim at identifying the codes of intracellular signals guiding retinal axons to the brain and shaping their arbors in their targets. We focus on signals required for axons to detect and interpret attractive and repulsive cues of axonal environment or involved in axonal and synaptic competition. Cyclic nucleotides and calcium are crucial for axons to integrate extracellular signals required for axon pathfinding and to modulate axonal and synaptic competition. They are involved in a wide range of other signaling pathways. We aim to decrypt the codes used by axons and synapses to identify such cellular messenger signals as specific regulators of neuronal connectivity. We use a combination of anatomical, imaging and optogenetic techniques to investigate the role of second messengers in the development of sensory maps. FRET imaging enables following cellular messenger concentration in living cells. Other techniques including subcellular targeting of cAMP, cGMP and calcium signaling blockers, and the use of light sensitive tools (optogenetics) make possible precise manipulations of these signals in time and space. Using these tools we are able to test the importance of local and temporal coding of cellular signals during the development of neuronal networks.
Second messengers modulate a wide range of cellular processes. We investigate the spatial and temporal features of cyclic nucleotide and calcium signals shaping neuronal connectivity to understand how second messengers achieve selectivity for their myriad of downstream pathways in developing axons.
Once axonal arbors are coarsely organized in their targets, complex and activity-dependent interactions between axons lead to the elimination of misplaced branches and synapses. This process requires interactions between neighboring axons. We aim to better understand these interactions between populations of axons.