Molecular Logic of Synaptic Diversity Between Drosophila Tonic and Phasic Motoneurons

Although neuronal subtypes often display unique synaptic organization and function, the underlying transcriptional differences necessary to establish these features is poorly understood. To identify molecular pathways that establish synaptic diversity, single neuron PatchSeq RNA profiling was performed on Drosophila tonic and phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while phasic motoneurons form stronger depressing synapses onto multiple muscles. Super-resolution microscopy and in vivo imaging demonstrated synaptic active zones in phasic motoneurons are more compact and display enhanced Ca2+ influx compared to their tonic counterparts. Genetic analysis identified unique synaptic properties that mapped onto gene expression differences in several cellular pathways, including distinct signaling ligands, post-translational modifications and intracellular Ca2+ buffers. These findings provide insights into how unique transcriptomes can drive functional and morphological differences between two closely related neuronal subgroups. PatchSeq RNA profiling of 105 1B motor neurons, 101 1S motor neurons, 17 M1 muscle cells and 26 M4 muscle cells.