Stimulation with a low-amplitude, digitized synaptic signal to invoke robust activity within neuronal networks on multielectrode arrays.

Multielectrode arrays (MEAs) are used for analysis of neuronal activity. Here we report two variations on commonly accepted techniques that increase the precision of extracellular electrical stimulation: (i) the use of a low-amplitude recorded spontaneous synaptic signal as a stimulus waveform and (ii) the use of a specific electrode within the array adjacent to the stimulus electrode as a hard-grounded stimulus signal return path. Both modifications remained compatible with manipulation of neuronal networks. In addition, localized stimulation with the low-amplitude synaptic signal allowed selective stimulation or inhibition of otherwise spontaneous signals. These findings indicate that minimizing the area of the culture impacted by external stimulation allows modulation of signaling patterns within subpopulations of neurons in culture. The simple modifications described herein may be useful for precise monitoring and manipulation of neuronal networks.