Strychnine analysis with neuronal networks in vitro: extracellular array recording of network responses

Neurons, by virtue of intrinsic electrophysiological mechanisms, represent transducers that report the dynamics of cell death, receptor-ligand interactions, alterations in metabolism and generic membrane perforation processes. In cell culture, mammalian neurons form fault-tolerant, spontaneously active systems with great sensitivity to their chemical environment and generate response profiles that are often concentration- and substance-specific. Changes in action potential patterns are usually detected before morphological changes and cell damage occur. This provides sensitivity and reversibility. Such biological systems may be used to screen rapidly for novel pharmacological substances, toxic agents and certain odorants. This paper reports on substance-dependent major changes in spontaneous native activity patterns by the synaptically active (glycine receptor blocker) strychnine. Via 64-channel array recordings of spontaneously active murine spinal cord cell cultures, increased multichannel bursting at 5-20 nM strychnine and regular, coordinated bursting above 5 microM could be reliably generated. By artificial neural network analysis a quantitative correlation of network signals and strychnine concentration could be evaluated for small concentrations of strychnine. The results indicate that cultured neuronal networks already represent reliable and practical systems which can be used for the detection of chemical substances and the characterization of their biological influences.