ABSTRACT

Studies of the neural basis of short lead interval startle modification have been one extension of the anatomical and behavioral “mapping” of the “primary startle circuit.” The neural substrates of prepulse inhibition (PPI) – an operational measure of sensorimotor gating – are studied partly because several neuropsychiatric disorders are characterized both by deficits in PPI and by clinical evidence of impaired inhibition of cognitive, sensory, or motor information. Brain regions implicated in the pathophysiology of these disorders – limbic cortex, ventral striatum, pallidum, and pontine tegmentum – critically regulate PPI. The neurochemistry of PPI includes neurotransmitters that subserve this circuitry, particularly dopamine, glutamate, serotonin, acetylcholine, and gamma-amino-butyric acid; specific neuropeptides also appear to regulate PPL These neural substrates have been studied via traditional neuropharmacological techniques in laboratory rats, via studies of PPI in specific patient populations, and via developmental and genetic manipulations. Collectively, these studies may identify perturbations of brain function in this circuitry that lead to deficits in PPI – such as those observed in schizophrenia and other disorders – and, conversely, what interventions might act at each level of the circuitry to enhance or restore normal levels of sensorimotor gating.