An evaluation of extracellular MEA versus optogenetic stimulation of cortical neurons

Abstract

Objective. The importance of extracellular neural stimulation has driven the development of multiple technologies. Of growing importance is accurately stimulating single neurons in dense networks. It is unlikely that one approach is best for all applications, however comparisons between methods are lacking. We aim to show the strengths and suitable applications for two tools; micro-electrode array (MEA) stimulation and optogenetics. Approach. We compare MEA-based electrical stimulation to Channelrhodopsin 2 based optogenetic stimulation of dissociated cortical neurons in vitro. Effectivity is compared based on stimulation success rate, spatial and temporal accuracy, and reproducibility. We discuss how necessities of each method may limit performance in each category. Main Results. MEA stimulation outperformed optogenetic stimulation in the speed with which an action potential could be generated. The relation between the size of the stimulating point (electrode or illumination spot) and the area of stimulated tissue was similar in both methods. However, technical difficulties in maintaining low impedance from very small electrodes allows higher spatial specificity in optogenetic stimulation. If simultaneous recording and stimulation are desired, MEA stimulation artifacts were far more impairing than light induce artifacts on MEA recordings. Significance. The like versus like comparison of stimulation technologies provides an incomplete evaluation tool for researchers desiring to apply these technologies. This comparison highlights advantages for specific applications and should promote more cross-topic evaluations.