Genetically-Encoded Neurotransmitter Sensor

These are protein sensors, expressed from a transgene, that report the concentration of a specific neurochemical by changing fluorescence — opening a window onto the chemical rather than the electrical dimension of signalling. Most are built by inserting a circularly-permuted fluorescent protein into a binding protein for the target: a native G-protein-coupled receptor for dopamine, acetylcholine, noradrenaline or serotonin (the GPCR-activation-based sensor family), or a periplasmic binding protein for glutamate. When the ligand binds, the fluorophore brightens.

Because they inherit the receptor's affinity and specificity and can be targeted to defined cell types and sites, they resolve neurotransmitter transients with subsecond timing and cellular spatial resolution in behaving animals — a capability that electrode-based electrochemistry cannot match for most modulators. They are distinct from the genetically-encoded calcium and voltage indicators of the graduate curriculum: those report a cell's own activity, while these report the chemical messages passing between cells.