neuroimaging tools have demonstrated that functional components of hippocampal circuits are very similar between animal models and humans.

PREPULSE INHIBITION

Neal Swerdlow, professor in the department of psychiatry at the University of California, San Diego, used the prepulse inhibition assay as a discussion case for the role of corresponding endpoints. Prepulse inhibition is defined as the automatic inhibition of the startle reflex, the contraction of the facial and skeletal musculature in response to an intense, abrupt stimulus, when the startling stimulus is preceded by a weak lead stimulus or prepulse. A primary measure of the startle reflex is movement of the orbicularis oculi muscle, or eye blink, often determined using surface electrodes attached to the muscles around the eye. In the laboratory, prepulse inhibition is an operational measure of sensorimotor inhibition, the inhibition of a motor response by a weak sensory event.

Prepulse inhibition is markedly diminished in a number of different neuropsychiatric disorders, including schizophrenia, Huntington’s disease, Tourette’s syndrome, Asperger’s syndrome, fragile X syndrome, and obsessive-compulsive disorder (reviewed in Braff et al., 2001). In schizophrenia, for example, patients show deficits in prepulse inhibition regardless of whether the startling stimulus is a tactile (e.g., an air puff) or acoustic stimulus. Although this phenotype is not specific to schizophrenia, it is robust and replicable.

Commonalities and Differences

From an experimental perspective, the stimulus delivery and response acquisition hardware and software that are used for prepulse inhibition testing are very similar across species. The most obvious difference in testing is physical restraint; human subjects voluntarily sit in a chair during testing while mice are enclosed in a tube.

The response characteristics are strikingly similar across species, including sensitivity to stimulus parameters (e.g., prepulse, intensity, and interval), cross-modal inhibition, habituation, and latency facilitation. That is primarily because the startle reflex involves neural circuitry that is common across all mammalian species, Swerdlow explained (Swerdlow et al., 1999, 2008). There are some obvious, although rela-



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement