Table 2.

Summary of fluorescent dopamine sensors

Name	Category	Functionality / excitation wavelength	Target	Advantages	Limitations
Dopamine (self)		2P microscopy/540 nm		direct detection of dopamine	low biopenetrance, sensitivity
Acridine orange	small molecule	fluorescence microscopy/460 nm	acidic compartments (synaptic vesicles)	pH sensitive; can detect release	only reported in cell culture; not specific to dopamine
FM1–43	small molecule	fluorescence microscopy/472 nm	cell membrane (synaptic vesicles, post-stimulation)	labels recycling vesicle pool	not neurotransmitter specific
FM4–64	small molecule	fluorescence microscopy/515 nm	cell membrane (synaptic vesicles, post-stimulation)	red, can be used in conjunction with blue and green sensors	not neurotransmitter specific
NeuO	small molecule	fluorescence microscopy/468 nm	live neurons	can be used in vivo; reported in mice and zebrafish	not neurotransmitter specific
FFN511	small molecule	fluorescence microscopy/406 nm; 2P/760 nm	DAT and VMAT2	selective for dopamine axons	less specific than later FFNs; most FFNs are limited to practical use ex vivo
FFN102	small molecule	fluorescence microscopy/406 nm; 2P/760 nm	DAT and VMAT2	pH sensitive; can detect release	not as bright when stored in vesicles
FFN200	small molecule	fluorescence microscopy/406 nm; 2P/760 nm	VMAT2	DAT independent, can detect silent synapses	longer incubation period and wash than other FFNs
FFN270	small molecule	fluorescence microscopy/406 nm; 2P/760 nm	NET, DAT, and VMAT2	pH sensitive; can detect release; has been used in vivo	more potent at NET than DAT
FFN206	small molecule	fluorescence microscopy/406 nm; 2P/760 nm	DAT, VMAT1, and VMAT2	useful for high- throughput studies, and fly imaging	less effective in mice
APP+	small molecule	fluorescence microscopy/416 nm; 2P/800 nm	DAT, NET, SERT	good monoamine sensor/high-throughput studies	not DA specific; labels mitochondria
NS521	small molecule	fluorescence microscopy/488 nm	monoamines	survives fixation	not DA specific
ES517	small molecule	fluorescence microscopy/488 nm	monoamines	adds pH sensitivity to NS521, can image release	not DA specific
nIRCat	nanoparticle	fluorescence microscopy/785 nm; 2P/1600 nm	dopamine, norepinephrine	near-IR sensor allows high biopenetrance; DNA sequence is tunable	not widely available; requires intracranial injection
CNiFER	HEK cell/protein sensor	fluorescence microscopy and fiber photometry/436 nm (FRET)	dopamine	does not require genetic manipulation	requires exogenous cell implant
DopR-Tango	genetic protein sensor	Postmortem analysis	D1R activation	good spatial resolution for post-synaptic analysis	requires 48 h postexcitation analysis
Name	Category	Functionality/excitation wavelength	Target	Advantages	Limitations
dlight/GRABDA	genetic protein sensor	fluorescence microscopy and fiber photometry/488 nm	Dopamine	Easy to introduce into mice and analyze dopamine release during behavior; newer generations come in red	newer approach, less characterized
VoLDeMo	targeted voltage-sensing dye	2P microscopy/920 nm	DAT; changes in voltage	can sense changes in voltage in DAT-expressing membranes (axons)	targeted probes have less dynamic range than untargeted voltage-sensing dyes
Voltron	genetic voltage- sensing protein + small molecule	fluorescence microscopy (FRET)/variable	changes in voltage	allows for fine experimental control based on which halo-tag dye is used	FRET approach is not amenable to 2P microscopy