The developmental history of the molecular synaptic code controlling excitatory connectivity, by Fekrije Selimi

Summary The developmental history of the molecular synaptic code controlling excitatory connectivity
The mature brain results from the formation of precise networks between functionally and morphologically distinct types of neurons. A given neuron forms synapses with a limited number of partners and on precise subcellular localizations. Understanding what controls this specificity is mandatory not only to understand brain functions but also the etiology of synaptopathies such as autism spectrum disorders or schizophrenia. Various molecules define the identity of each type of synapse. Furthermore, neuronal activity- dependent mechanisms sculpt and stabilize neuronal connectivity. Our team’s work aims at dissecting how neuronal activity controls the molecular identity of synapses with the postulate that this regulation occurs through mechanisms specific for each neuronal population, thereby regulating synapse specificity. We focus on the olivocerebellar network, which is involved in motor control and also in cognitive processes.

Short Biography
My research aims at dissecting the molecular basis of the development of a functional brain taking in account the diversity of neuronal types and synapses. My PhD in the laboratory of Pr. Jean Mariani (1995-2000, UPMC) consisted in looking at the specificity of neurodegeneration mechanisms in different neuronal populations in the mouse brain. During my training as a postdoctoral fellow in the laboratory of Pr. Heintz (2001-2007, Human Frontier Science Program, Rockefeller University, USA), I undertook a project aiming at identifying the protein composition of specific synapses in vivo in the mouse in order to unravel a potential “synaptic code”. I developed a new strategy, ‘the synapse protein profiling” approach, combining transgenesis, biochemistry and mass spectrometry. This work is the first example of the purification of a specific synapse type from a particular neuronal population. As a CNRS researcher (2007-present), I followed up on this work and went on to describe new molecular signaling pathways that control neuronal development. In 2011, I set up my own independent team at the CIRB, Collège de France with first an award from the ATIP-AVENIR, then from the Fondation pour la Recherche Médicale. We combined the synapse protein profiling strategy with the bacTRAP technology to perform the first comparison of the composition of two excitatory synapses made on the same target neuron to directly test the idea of a molecular synaptic code. These studies allowed us to decipher new synaptic signaling pathways that regulate brain development and might be involved in neurodevelopmental diseases. In 2016, I received a consolidator grant from the European Research Council to study how identify the molecular synaptic code in cerebellar Purkinje cells and how it is established during development.