Abstract for NSF proposal: IBN - 9723871 A significant problem for biomedical research of nerve tissue is the local stimulation of dendrites with bioactive substances such as neurotransmitters. The methods for electrical stimulation that are commonly used can only reach electrically excitable membranes and cannot directly activate the receptors of neurotransmitters. There exist chemically inactivated and photolabile substances that allow for adequate chemical stimulation. These so called caged compounds can be activated by disruption of their molecular cage with a flash of ultra-violet light. However, current photolysis systems used for this purpose lack speed and/or spatial accuracy. Multisite photolysis with high spatio temporal resolution of caged compounds would permit experiments in isolated nerve tissue that closely resemble the situation in the intact nervous system. This capability would add a new dimension to neuroscience and related biomedical fields. It is proposed to develop an optical stimulation system to locally release caged bioactive compounds by means of a pulsed, scanning UV laser beam. This novel system will make use of a scanning principle that allows for ultrafast, accurate, and computer-controlled random-positioning of laser beams. The proposed solution will exceed the capability of previous photolysis systems in its flexibility and spatio-temporal resolution by using acousto-optical effects to control position and intensity of the laser beam. With such devices, positioning and modulation times are in the microsecond range, permitting simultaneous multi-site release of caged compounds and thus multi-site stimulation.
