Technique,Advantages,Disadvantages
Electron Microscopy,Provides detailed wiring diagram of small volumes.,Time and labor-intensive. Impractical for long-range connections or for many samples.
Synaptic Tagging,Can monitor synapses in vivo.,For regions dense with synapses, super-resolution microscopy may be required. Need genetic drivers for putative synaptic partners.
GRASP,Can monitor synapses in vivo. With NSyb::GRASP, can specifically detect active synapses.,May be not sensitive enough for in vivo detection. Can induce irreversible binding at natively transient synapses.
PA-GFP,Can be used for unbiased identification of novel synapses.,Not conclusive by itself. Requires functional studies to confirm.
WGA,Only requires a single transgene. Simple to implement.,Can result in labeling of higher-order synapses. The signal can be difficult to detect because it gets diluted.
Tango-Trace,Can identify functional synapses. Allows genetic manipulation based on synaptic input.,Requires prior knowledge of neurotransmitters. Requires a way of artificially stimulating the presynaptic neuron of interest.
TRACT,Allows genetic manipulation based on cell-cell contact.,Requires optimization to trace neuron-neuron connections.