A Picture Worth a Thousand Molecules-Integrative Technologies for Mapping Subcellular Molecular Organization and Plasticity in Developing Circuits.

A key challenge in developmental neuroscience is identifying the local regulatory mechanisms that control neurite and synaptic refinement over large brain volumes. Innovative molecular techniques and high-resolution imaging tools are beginning to reshape our view of how local protein translation in subcellular compartments drives axonal, dendritic, and synaptic development and plasticity. Here we review recent progress in three areas of neurite and synaptic study in situ-compartment-specific transcriptomics/translatomics, targeted proteomics, and super-resolution imaging analysis of synaptic organization and development. We discuss synergies between sequencing and imaging techniques for the discovery and validation of local molecular signaling mechanisms regulating synaptic development, plasticity, and maintenance in circuits.