Photolytic uncaging of neurotransmitters as a control and stimulation device for neural tissues

Methods are available that can 'cage' neurotransmitters, precluding them from binding with receptors in the nervous system. They are thus rendered biologically inert until photolytic uncaging cleaves their 'cage'. We explored uncaging of MNI-glutamate with implanted fiber optics as a stimulation technology. The spinal cord was bathed in the caged glutamate at different concentrations, and a flash photolysis unit projected brief, spatially concentrated bursts of light into the lumbar spinal cord through a fiberoptic light guide. Forces generated at the ankle were measured in 3 dimensions. Responses were tested at discrete depths in the lumbar cord, with the strongest responses located in the 900 to 1100 μm range. Our results indicate feasibility of this approach for engineering a neuroprosthesis. The advantage of this technology is that in principle excitation, inhibition, and modulation state of neural circuits can all be controlled.