Real-time Bidirectional Communication with Neuronal Cultures
Substrate-Integrated Micro-Electrode Arrays, Reutlingen, Germany, July 2004
Multi-electrode arrays (MEAs) enable researchers to electrically communicate with large numbers of cells in a neuronal culture. Technology to record from 60 electrodes simultaneously has been commercially available for many years. By contrast, stimulation studies have mostly been limited to small numbers of electrodes. In this talk I will describe a device that allows stimulation of any of 60 electrodes with real-time software control over channel selection. The device can be directly plugged into MultiChannel Systems MEA preamplifiers, is inexpensive to produce, and can easily be modified for use with other recording hardware.
Using this device to stimulate high-density cultures of cortical neurons, we found that any electrode that is in sufficiently close contact with the culture to record activity, can also be used to evoke activity. We quantified the efficacy of a range of stimulus pulse shapes, both under voltage- and current-control, and found that voltage-controlled, biphasic, positive-phase-first pulses are the most effective stimuli for any given peak-voltage quotum. This is good news, because voltage-controlled stimuli have the added advantage that electrochemistry can be explicitly controlled, make their use considerably safer than current-controlled stimuli.
By connecting this stimulator to our freely available data acquisition software, MeaBench, we close the feedback loop between cell culture and computer. The system can generate stimuli in response to recorded action potentials within 15 ms, a timescale that corresponds to only a few typical cortical neuron-to-neuron propagation delays, and similar to the time constant of NMDA channels. Thus, we can now communicate bidirectionally through a 60-channel-wide channel with cortical cultures, at a tempo that matches the neurons’ own.