Behavioral seizure correlates in animal models of epilepsy: A road map for assay selection, data interpretation, and the search for causal mechanisms

Abstract: A broad spectrum of learning/memory, social interaction, and affective behavioral measures serve as functional correlates for neurobiological changes in seizure-prone animals as well as in epileptic clinical populations. The utility of such measures is demonstrated by their ability to distinguish anomalous characteristics in developing organisms predisposed to seizure onset, as well as to discriminate prior seizure history in organisms with established pathology. For instance, typical findings that generalize across species suggest that seizure-experienced organisms exhibit a variety of deficits in cognitive function as well as inappropriate social neglect and aggression. Behavioral testing batteries have also proven useful in assessing neural mechanisms for seizure induction, subcortical neural circuits, and neuropeptide modulators, for example, as well as in identifying neural pathology resulting from prior seizure activity. However, the wanton application of behavioral tests can also produce false positives in the identification of seizure-related disorders unless alternative performance and motivational hypotheses are discounted effectively. Accordingly, the present review attempts to provide the reader interested in behavioral phenotyping and characterization of seizure-prone rats and mice with a roadmap for rational selection, implementation, and interpretation of data from behavior assays while highlighting potential successes and pitfalls inherent in employing functional correlates of brain activity using animal models of epilepsy. [Copyright &y& Elsevier]