Dynamics and function of the neurexin-neuroligin adhesion complex in synapse assembly and plasticity
Centre Broca Nouvelle-Aquitaine
Understanding the complex map of neural connectivity in the mammalian brain has become one of the major goals of modern neuroscience. Fundamental to such efforts is the elucidation of the mechanisms that wire up, sculpt and maintain synaptic connections. Cell adhesion proteins including pre-synaptic neurexins and their post-synaptic partners neuroligins play important roles in these mechanisms. Moreover, genetic mutations in these molecules have been related to autism spectrum disorders in humans. By combining super-resolution microscopy, electrophysiology and optogenetic approaches, we are investigating the dynamic organization of these molecules and how they contribute to the recruitment of scaffolding proteins and glutamate receptors in front of appropriate presynaptic terminals. We recently discovered a phosphorylation signaling targeting neuroligin-1 which controls the recruitment of glutamatergic receptors at synapses upon binding to presynaptic neurexin and which occludes LTP. Importantly, this signaling can be triggered optogenetically and allows for an acute control of endogenous neuroligin-1 function. Besides clarifying the role of neuroligin-1 at excitatory synapses, our optogenetic approach provides the exciting opportunity to control in time and space synaptic connectivity and function, and therefore paves the way for investigating the possible contribution of neuroligins to neuropsychiatric behaviors.
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