Experimental Platform for the Study of Region Specific Excitation and Inhibition in Neural Tissue

Willfully controlling the focus of an extracellular stimulus remains a significant challenge in the development of neural prosthetics and therapeutic devices. In part, this is due to the fact that experimental validation of the evoked response to stimuli is an arduous and time-consuming task. The development of a high-throughput data acquisition and analysis tool would greatly facilitate the design of spatially selective stimulation protocols. We present an automated imaging system that can optically track and identify the action potentials of individual neurons evoked by coordinated stimulus waveforms applied at multiple electrodes. This system can simultaneously provide arbitrary current waveforms to four electrodes, and it is capable of automatically monitoring the cellular responses of every neuron in a cultured network within a 1.6 x 1.6 mm area. The purpose of this platform is to develop stimulus protocols that exploit the benefits of multi-polar field shaping and temporal ion-channel manipulation to localize cellular excitation beyond the vicinity of the electrode. Preliminary single electrode experiments demonstrate that spatially selective stimulus suppression may be achieved with cathodic, depolarizing pre-pulses that induce a sub-threshold refractory state in neighboring neurons. Coordinated, multi-site stimuli could potentially take advantage of this refractory state to direct the stimulus focus away from the surrounding area of the electrode and into the inter-electrode spaces.