Cross-species studies of sensorimotor gating of the startle reflex

Sensorimotor gating of the startle reflex can be assessed across species, using similar stimuli to elicit comparable response characteristics. As measured by prepulse inhibition (PPI), gating is reduced in patients with some neuropsychiatric disorders, and in rats after manipulations of limbic cortex, striatum, pallidum, or pontine tegmentum. This limbic "CSPP" circuitry can be studied in rats to reveal the neurochemical and neuroanatomical substrates regulating PPI at a high level of resolution. This detailed circuit information is used as a "blueprint" to identify substrates that may lead to PPI deficits in psychiatric-disordered humans. Some human disorders with identifiable, localized lesions in CSPP circuitry, for example, Huntington's disease, provide direct validation for this cross species model. Studies have begun to assess the pharmacological homology of PPI across species, as an initial step towards translating detailed neural circuit information from rats to humans. These initial studies suggest the possibility that the effects of dopaminergic (DAergic) drugs on PPI (reducing PPI) may be homologous across species; nicotinic drugs may also produce similar effects on PPI across species (increasing PPI). By contrast, the effects of glutamatergic and serotonergic drugs may exhibit disparate effects on PPI across species. The use of DAergic agonists in human studies is complicated by their significant side effects, but new studies demonstrate that several "human friendly" direct DA agonists disrupt PPI in rats and are thus good candidates for further studies of the cross species homology of the DAergic regulation of PPI. In this manner, PPI can be used to probe the sensitivity of DAergic systems, and perhaps other CSPP elements, across normal and neuropsychiatric disordered populations.