Prepulse inhibition of the acoustic startle reflex and P50 gating in aging and alzheimer's disease

Inhibition plays a crucial role in many functional domains, such as cognition, emotion, and actions. Studies on cognitive aging demonstrate changes in inhibitory mechanisms are age- and pathology-related. Prepulse inhibition (PPI) is the suppression of an acoustic startle reflex (ASR) to an intense stimulus when a weak prepulse stimulus precedes the startle stimulus. A reduction of PPI is thought to reflect dysfunction of sensorimotor gating which normally suppresses excessive behavioral responses to disruptive stimuli. Both human and rodent studies show age-dependent alterations of PPI of the ASR that are further compromised in Alzheimer's disease (AD). The auditory P50 gating, an index of repetition suppression, also is characterized as a putative electrophysiological biomarker of prodromal AD. This review provides the latest evidence of age- and AD-associated impairment of sensorimotor gating based upon both human and rodent studies, as well as the AD-related disruption of P50 gating in humans. It begins with a concise review of neural networks underlying PPI regulation. Then, evidence of age- and AD-related dysfunction of both PPI and P50 gating is discussed. The attentional/ emotional aspects of sensorimotor gating and the neurotransmitter mechanisms underpinning PPI and P50 gating are also reviewed. The review ends with conclusions and research directions.