STRYCHNINE ANALYSIS WITH NEURONAL NETWORKS IN-VITRO - EXTRACELLULAR ARRAY RECORDING OF NETWORK RESPONSES

Neurons, by virtue of intrinsic electrophysiological mechanisms, repre sent transducers that report the dynamics of cell death, receptor-liga nd interactions, alterations in metabolism and generic membrane perfor ation processes. In cell culture, mammalian neurons form fault-toleran t, spontaneously active systems with great sensitivity to their chemic al environment and generate response profiles that are often concentra tion- 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 m ay be used to screen rapidly for novel pharmacological substances, tox ic agents and certain odorants. This paper reports on substance-depend ent major changes in spontaneous native activity patterns by the synap tically active (glycine receptor blocker) strychnine. Via 64-channel a rray recordings of spontaneously active murine spinal cord cell cultur es, increased multichannel bursting at 5-20 nM strychnine and regular, coordinated bursting above 5 mu M could be reliably generated. By art ificial neural network analysis a quantitative correlation of network signals and strychnine concentration could be evaluated for small conc entrations 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 characterizatio n of their biological influences. (C) 1997 Elsevier Science Limited.