Photoconductive stimulation of neurons cultured on silicon wafers

Photoconductive stimulation allows the noninvasive depolarization of neurons cultured on a silicon wafer. This technique relies on a beam of light to target a cell of interest while applying a voltage bias across the silicon wafer. The targeted cell is excited with minimal physiological manipulation, and, therefore, long-term modulation of activity patterns and investigations of biochemical mechanisms sensitive to physiological perturbations are possible. Ideologically similar to transistor-based neuronal interfaces, the photoconductive-stimulation method has the advantage of being able to extracellularly excite any neuron in a network regardless of its spatial position on the silicon substrate. This protocol can be easily implemented on a conventional reflected-light fluorescence microscope using materials and resources that are readily available. Time requirements are comparable to standard cell-culture and electrophysiology techniques. When combined with fluorescence imaging of various molecular probes, activity-dependent cellular processes can be dynamically monitored.