Richard Weir, Associate Research Professor in the Department of Bioengineering, and colleagues receive funding to develop an Optical Probe capable of Activating/Reporting on axon activity in nerves of parasympathetic nervous system. Current neuro-modulation approaches for the vagus nerve (aka parasympathetic nervous system) are generally all or nothing events that cause simultaneous changes in heart rate, for example, along with changes in pancreatic function. Our goal for this project is to develop a novel compact Optogenetic based Optical Probe capable of optically neuromodulating individual afferent and/or efferent axons within nerves of the parasympathetic, or peripheral, nervous system. We seek to read-in or read-out from these nerves with the goal of modulating the organs or brain circuits innervated by them.
Our central premise is that we can use optics to communicate with axons in a nerve. For optical approaches to work we need to convert action potentials into an optical signal. This can be done using reporter proteins or by some other means that is ancillary to action potential generation. Because nerves do not naturally express optical proteins, we will work with transgenic mice that express these proteins and use these mice to refine our system before making it available for other researchers to use. We are proposing to couple an optical fiber with an electrowetting lens head to allow remote interrogation of the vagus nerve with a bench top (i.e. portable) laser system. Integration of miniature (1mm diameter) scale electrowetting electrically tunable optics with an optical fiber-based imaging system will enable two-photon fluorescence imaging of neuron activity by readout of a fluorescent indicator.
We will work with collaborators in the field of pancreatic research to test, refine and demonstrate our ability to activate/report from in-vitro mouse vagus nerves and to see if we can control and/or sense pancreatic responses in the absence of other responses, such as a change in heart rate, using targeted neuro-modulation of specific axons in the vagus in in-vivo transgenic mice experiments.