Animal models of deficient sensorimotor gating: what we know, what we think we know, and what we hope to know soon

Sensorimotor gating of the startle reflex can be studied in humans and labo ratory animals using measures of prepulse inhibition (PPI) of the startle r eflex. PPI is reduced in patients with specific neuropsychiatric disorders and in rats after manipulation of the limbic cortex, striatum, pallidum or pontine tegmentum. Studies are rapidly identifying the neurochemical and ne uroanatomical substrates regulating PPI in laboratory animals; this detaile d circuit information has been used as a 'blueprint' to identify possible c andidate substrates responsible for PPI deficits in psychiatrically disorde red humans. In parallel, studies have also begun to assess the homology of pharmacological effects on PPI across species, as an initial step towards t ranslating detailed neural circuit information from rats to humans. Despite this rapid progress, there is an increasing danger of overlooking importan t methodological and interpretative issues that could impact either positiv ely or negatively on the ultimate utility of models based on measures of PP I. Some of these issues ranging from the cross-species methods for quantify ing specific variables to the relevance of genetic drift to animal and huma n studies of PPI - and their implications for future studies are the focus of this review. (C) 2000 Lippincott Williams & Wilkins.