New technologies for imaging synaptic partners

Understanding the brain will require unraveling its synaptic circuitry, but methods that can reliably identify connected neurons are often excruciatingly slow. Although light microscopy can provide much higher throughput, synapses are smaller than the diffraction limit and cannot readily be assigned to particular presynaptic and postsynaptic cells without specialized labeling methods. Here we review the ongoing development of techniques that allow direct imaging of neural networks by specifically marking connected cells or their synapses.

► Wiring diagrams are essential but difficult to obtain. ► Light microscopy cannot resolve synaptic connections with conventional labeling methods. ► New molecular methods increase labeling resolution. ► Monosynaptic tracing labels directly connected cells using transcomplemented viruses. ► GRASP labels specific synapses between genetically defined cells in vivo.