Photostimulation with caged neurotransmitters using fiber optic lightguides

'Caged' neurotransmitters are molecules that are transformed to a neuroactive state by exposure to light of an appropriate wavelength and intensity. Use of these substances has centered on in vitro bath application and subsequent activation using light from lasers or flashlamps that is delivered into the preparation through microscope optics. We have tested a new and simpler method, using finely tapered fiberoptic lightguides, that promises to expand the use of caged compounds for in vitro and in vivo experimentation. We demonstrated the feasibility and flexibility of this method for caged neurotransmitter delivery using a range of ex vitro, in vitro and in vivo approaches. The degree and timing of uncaging could be controlled by manipulating the wavelength, intensity and timing of the light projected into the optical fiber. Because of the small size of the light guide and the ability to control light exposure at the source, this new method promises greater control over the spatial and temporal delivery of neuroactive substances than simple bath or iontophoretic application, and enables delivery of conventional neurotransmitters with a spatial and temporal resolution closer to that of the natural neuronal circuitry. In addition, this new method allows the application of normally labile substances, such as the free radical gas nitric oxide, by the photoconversion of photosensitive precursors.