Use of neurophysiological challenges for the detection of toxicity

The concept that a challenge to a system may overcome compensatory mechanisms and thereby reveal otherwise hidden neurotoxicant-induced damage is reviewed from a neurophysiological perspective. Two broad classes of neuronal challenges, poststimulation neuronal recovery processes and epileptogenesis, are discussed in terms of their potential value for detection and characterization of neurotoxicity. Neuronal recovery studies have typically involved presentation of pairs or trains of stimuli with various interstimulus intervals. Studies involving simple (e.g., monosynaptic) systems may allow mechanistic interpretation of alterations. Paired-pulse studies involving more complex (e.g., polysynaptic sensory) systems have detected alterations more readily than other electrophysiological methods, but interpretation may not be as straightforward as the monosynaptic case. The properties of elicited seizures, as well as the threshold for production of seizures, have been used with some success for detection of neurotoxicity. Several seizure models are discussed. It is concluded that both classes of neuronal challenge hold promise for future studies of neurotoxicity.