PHOTOSTIMULATION WITH CAGED NEUROTRANSMITTERS USING FIBER OPTIC LIGHTGUIDES

'Caged' neurotransmitters are molecules that are transformed to a neur oactive state by exposure to light of an appropriate wavelength and in tensity. Use of these substances has centered on in vitro bath applica tion and subsequent activation using light from lasers or flashlamps t hat is delivered into the preparation through microscope optics. We ha ve tested a new and simpler method, using finely tapered fiberoptic li ghtguides, that promises to expand the use of caged compounds for in v itro 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 ti ming of uncaging could be controlled by manipulating the wavelength, i ntensity and tinting of the light projected into the optical fiber. Be cause 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 con ventional neurotransmitters with a spatial and temporal resolution clo ser to that of the natural neuronal circuitry. In addition, this new m ethod allows the application of normally labile substances. such as th e free radical gas nitric oxide, by the photoconversion of photosensit ive precursors. (C) 1997 Elsevier Science B.V.