Parameters for Voltage- and Current-controlled Stimulation of Cortical Cultures Through Multi-electrode Arrays
33rd Annual Meeting of the Society for Neuroscience, New Orleans, LA, 2003
We electrically stimulate cultures of dissociated neurons from rat cortex growing on MEAs, with two goals: 1. We study the influence of patterned stimulation on the development of functional connectivity in living neural networks. 2. We use electrical stimuli to convey an animat’s or hybrot’s sensory input to the culture which is its brain. For both, detailed knowledge of the impact of different stimulation parameters is indispensible. We find that cathodic current pulses are effective stimuli. Both very short but strong (50 uA x 20 us), and very weak but prolonged (5 uA x 1 ms) stimuli elicited network response. No responses to any anodic pulses were observed. While current-controlled pulses are attractive, the required hardware is difficult to implement for many electrodes. Therefore, we also studied voltage-controlled pulses. Biphasic, anodic-first, square waveforms were most effective, due to the cathodic current spike accompanying the voltage transient between the two phases. The response patterns to these stimuli remain stable for several days in mature cultures. On the other hand, by sending in trains of stimuli at frequencies between 0.1 Hz and 100 Hz, we determined that responses are relatively suppressed at rates above 1 Hz. During continued high-frequency stimulation on one electrode, responses to stimulation on another electrode are not reduced, so we think this suppression is due to ionic or vesicle depletion in directly stimulated cells. These findings drive the design of our next generation of stimulators. Moreover, the parameter space of stimuli that retain their efficacy upon repeated presentation is an essential resource for studying the influence of continuous stimulation on development. It could also benefit animal studies involving extracellular stimulation, and have clinical implications for deep brain stimulation and control of epilepsy.