A Windows-programmable multi-channel stimulator for generating patterned input and inducing plasticity in cortical networks in vitro
Wilson, N.R. 1, Shi, B.1, Daitch, A.L.2 and Sur, M.1
1Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge MA, USA
2Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge MA, USA
The response properties of synapses, neurons and maps in cortical networks are believed to be specified at least in part by patterned activity from their inputs. To understand the mechanisms by which activity patterns are transduced into connectivity changes, we sought the ability to deliver programmable stimulation patterns across multiple sites of a network of cortical neurons cultured on a multi-electrode array (MEA). Such tools have recently been developed commercially and by research groups in the form of multi-channel stimulators, and we aimed to develop a version that made use of standard, readily available parts, and that was compatible with the most ubiquitous interface (USB), operating system (Windows) and programming environment (Matlab) to facilitate customization by researchers. We present a design that allows waveforms to be arbitrarily programmed in Matlab and then delivered to 64 channels in user-defined patterns, either in disparate sequences or in tandem. The timing of delivery is controlled by hardware and is not subject to operating system delays, and the “plug and play” nature of the system makes the interface apparent to the user only for the customization of stimuli. Most importantly, this system allows patterned stimulation to be arbitrarily integrated with other computer-controlled modules, such as patch clamp recording, to enable ‘feedback loops” between stimulation and recording. We present one application of this system in which patterned stimulation is used to drive multiple inputs converging on a single neuron, and the concurrent measurement of the strength of these inputs enables a computer-assisted search for patterns of activity that result in heterosynaptic changes of the cell’s response properties.