Development of photoconductive stimulation technology for long-term interfacing with living neurons.

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Traditionally, the study of cognitive brain function has been approached through the use of either human subjects or animal models. However, technological advances from the last few decades now allow us to use in vitro neuronal systems to investigate in high resolution the underlying mechanisms responsible for higher level brain functions. Understanding and developing technology to investigate neuronal activity patterns has many applications: from directly facilitating our understanding of complex dynamical systems through to the creation of drug screening devices and modeling of neuropathological conditions. Essential to this research has been the development of devices and systems that allow one to both stimulate and record from living neuronal networks. One such technology, photoconductive stimulation, was invented by my colleagues and I in the lab of Yukiko Goda at UCSD. Based on the principle that the conductivity of silicon will change when illuminated by visible light, neurons are first grown on the surface of specifically manufactured silicon wafers. Then, by optically targeting them with light, they can be individually triggered to fire at a user-defined frequency or in a specific non-random pattern. Combined with calcium- or voltage-sensitive dye imaging of the neuronal network's electrical activity, simultaneous two-way communication with hundreds of neurons has become a reality. This proposal seeks to extend the photoconductive stimulation technology in the following ways, for the following specific goals:******1) Development of a long-term neuronal-silicon interface chamber and stimulation methodology for extended or even permanent interfacing with living neuronal cultures.***2) Development of the in situ optical activity recording devices and protocols, to facilitate extended high resolution recording and analysis of neuronal activity.******Central Hypothesis: Through the use of an optically-based neuronal/silicon interface, we have established a non-invasive methodology to gain read/write capability with living neuronal networks. By developing a long-term controlled environment that maintains this functionality, we can pursue critical questions as to the effect of environmental and genetic manipulation of brain circuits, as well as obtain high spatial- and temporal-resolution data necessary to accurately analyze the complex system dynamics of living neuronal networks.******We believe the development of a viable long-term neuronal interface platform will not only bring immediate gains in our understanding of brain function and complex dynamical systems, but will also have numerous applications for integrating with other research and commercial goals.**