Coordination of Synaptogenesis and Neurotransmitter Receptor usage – BuildSynapse

Neuronal circuit function is defined by synaptic wiring with subcellular precision, which is itself dependent on the distribution of Neurotransmitter Receptors (NTRs) onto postsynaptic dendritic arbors. However, little is known on the developmental mechanisms that establish synaptic subcellular distribution, and whether and how these processes are linked with the usage of specific NTRs in each synapse to receive input from the corresponding presynaptic neuron. We will address this question by exploring in vivo, the cellular interactions and molecular players that orchestrate synapse formation, and the post-transcriptional regulation events that recruit NTRs to post-synaptic terminals during synaptogenesis. As a paradigm, we will use the T4 neurons in the Drosophila Optic Lobe, the fly’s visual processing center. Each T4 receives input from different upstream neurons by clustering distinct NTRs to discrete dendritic areas. Our preliminary data shows that in T4s, mRNAs coding for NTRs subunits are expressed 3 days before their protein is produced and synapses are formed. We hypothesize that post-transcriptional events should synchronize mRNAs-translation and NTRs recruitment to the corresponding synapses during synaptogenesis. Single-cell approaches will be combined with genetic tools, endogenously tagged NTRs, single molecule RNA detection techniques, in vivo translation imaging and super-resolution microscopy to: 1) Define spatiotemporal patterns of synaptogenesis and NTRs expression in T4s dendrites, 2) Dissect the post transcriptional regulation of NTRs spatiotemporal expression, 3) Test the role of cellular contacts and synchronized neural activity between T4 and presynaptic neurons in regulating NTR expression in developing T4 dendrites. Our multi-level approach will identify cellular interactions and molecular players that orchestrate synapse formation, and provide seminal insights into the function of activity and mRNA regulation during neurodevelopment.