Table 1:

Summary of Dopamine Sensing Modalities

Modality	Description	Spatial Resolution / Level of Analysis	Temporal Resolution	Advantages	Limitations
Microdialysis	A small dialysis probe is surgically implanted into the brain and analytes are collected over time	mm-cm / brain regions (e.g. dorsal lateral striatum)	seconds - minutes	HPLC separation allows complete analysis of small molecules within dialysate; can be used in an awake, behaving, free moving animal	Poor spatiotemporal resolution
FSCV	A redox electrode is inserted into slice or surgically implanted and the concentration of dopamine is electrochemically measured	mm / brain region; specific circuits if coupled with electro- or optogenetic stimulation	milliseconds	High temporal resolution; can be used in acute brain slice or behaving animals	Poor spatial resolution; difficult to implement in vivo
Fluorescent Microscopy	Small molecule- or protein-based sensors are used to indirectly monitor or measure dopamine release in slice or culture	μm - mm / synapses (e.g. release sites, cell bodies and projections)	milliseconds - seconds	High spatiotemporal resolution; diverse set of fluorescent dyes and protein sensors	Low biopenetrance and small wavelengths can be phototoxic; limited use in vivo
2P Microscopy	Fluorescent sensors are imaged using two-photon excitation, typically at twice the wavelength	μm - mm / synapses	milliseconds - seconds	Longer wavelengths used in 2P allow higher biopenetrance and less phototoxicity; in vivo imaging is possible	Expensive and complicated to implement; biopenetrance is still limited to 10s – 100s of μm; incompatible with FRET sensors
Fiber Photometry	A fiberglass fluorescence probe is surgically implanted into the brain; changes in fluorescence intensity of genetic probes are measured over time	mm / brain region; specific circuits	milliseconds - seconds	Protein sensors can be used in vivo in behaving animals; widely adaptable in labs already measuring GCaMP	Limited spatial resolution
PET	Positron-emitting ligands can target specific receptors in order to monitor dopaminergic activity	mm / brain region	minutes	High sensitivity (i.e. small amount of ligand needed) with a diverse set of ligands; can be used in humans and coupled with behavior	Ligands are expensive, difficult to synthesize, and can have short half-lives; poor spatiotemporal resolution, impossible to resolve ligand signal from its metabolite signal
MRI	Magnetic resonance is used to image endogenous dopamine metabolites or exogenous MR-active ligands	sub-mm - mm	milliseconds - seconds	Potentially non-invasive, can be used in humans and coupled with behavior; ligands can be used to increase spatiotemporal resolution or highlight specific structures	Information is largely structural and not functional
MRS	Magnetic resonance is used to generate spectra that can identify specific metabolites and their relative concentrations	mm-cm	seconds - minutes	Can identify and resolve multiple molecules and their relative concentrations within the same voxel, including ligands from their respective metabolites	Highly specialized technique, lower spatiotemporal resolution than MRI and PET; certain nuclides (13C, 15N, and 31P) can have very long scan times