Background

Sensorimotor gating refers to the ability of a sensory event to suppress a motor response (Cryan and Reif, 2012). One form of sensorimotor gating that has been widely studied in humans and rodents is the prepulse inhibition (PPI) of startle. The startle reflex consists of involuntary contractions of whole-body musculature elicited by sufficiently sudden and intense stimuli. Specifically, the acoustic startle response is characterized by an exaggerated flinching response to an unexpected strong auditory stimulus. PPI is a form of startle plasticity and it is characterized by a normal reduction in startle magnitude that occurs when an intense startling stimulus (or pulse) is preceded by a brief, low intensity prestimulus (or prepulse) (Graham, 1975; Hoffman and Ison, 1980). The PPI paradigm is commonly used to evaluate sensorimotor gating and it has been described in numerous species, including humans (Schwarzkopf et al., 1993) and mice (Carter et al., 1999; Frankland et al., 2004). Impaired PPI is observed in schizophrenia (Braff et al., 2001; Swerdlow et al., 2008), as well as other neuropsychiatric disorders including obsessive-compulsive disorder (Ahmari et al., 2012), Tourette’s syndrome (Swerdlow et al., 2001), Huntington’s disease (Swerdlow et al., 1995) and bipolar disorder (Perry et al., 2001). In patients with psychotic disorders, deficits in sensorimotor gating are associated with cognitive fragmentation and psychotic symptoms (Kapur, 2003). As these deficits have been found both in psychotic patients as well as in animal models (Swerdlow and Light, 2016), the PPI paradigm is largely used in the study of neuropsychiatric diseases and has proven a useful tool for studying and characterizing the effects of several anti-psychotics (Xue et al., 2012), and for exploring the mechanisms underlying psychotic-like behaviors (Geyer, 1999; Ouagazzal et al., 2001).