A new device is described, called the Photoliberator, that delivers pharmacological agents to the central nervous system from """"""""caged"""""""" compounds. These compounds conserve their biological activity until released by light energy of the appropriate wavelength. Because neuroactive molecules are generated in proportion to light intensity, the Photoliberator provides better control of timing and dosage of neurotransmitters than microiontophoresis and pressure injection. It also enables the controlled deliver of volatile species. such as the free radical gas Nitric oxide (NO). NO has been implicated in many important physiological roles. including blood pressure regulation and memory formation, but the direct application of NO to in vitro and in vivo neuronal preparations is limited by its short half life (about 5 sec). Using the Photoliberator, the caged fond of NO can be applied and activated in separate steps. Other caged compounds can be delivered and activated by this device, including caged glutamate and caged Ca--, which enhances its utility as a general purpose neurophysiological tool. A three-stage experimental approach. ranging from ex vitro to in vivo preparations is proposed to test a series of more powerful prototypes. The Phase Il research effort will culminate in the commercialization of this device.
An economical, fast and quantitative method for delivery of nitric oxide in living animal models with intact neuronal and vascular circuitry will find a growing market with physiological researchers worldwide. The Photoliberator can also deliver other caged compounds, and exceeds the performance of conventional technologies for neuronal stimulation.
