Prepulse Inhibition

Purpose

To explore genetic and neurobiological mechanisms underlying behaviours of relevance to psychosis

Description

This method is an acoustic startle model of sensorimotor gating where a weak acoustic stimulus (the pre-pulse) is used to decrease the reflex response (startle) produced by a second, more intense, stimulus (the pulse) in mice. Pre-pulse inhibition (PPI) provides an operational measure of sensorimotor gating which reflects the ability of an animal to inhibit sensory information. Schizophrenic patients have a reduced PPI. The lack of sufficient sensory gating mechanism is thought to lead to an overflow of sensory stimulation and disintegration of cognitive functions. Hence, PPI is largely used to assess the effects of antipsychotics and to explore genetic and neurobiological mechanisms underlying behaviours of relevance to psychosis.

Figure 1. PPI of the Acoustic Startle Response in Disc1 mutant mice. (a) Disc1-Q31L and Disc1-L100P mutants expressed PPI deficits at all three pre-pulses compared with their WT littermates (Clapcote et al. 2007. Neuron. "Behavioral phenotypes of Disc1 missense mutations in mice" 54(3):387-402).

Figure 2. (b) Disc1-L100P mutants with severly impaired PPI also showed lowered the Acoustic Startle Response in comparison with WT mice (Clapcote et al. 2007. Neuron. "Behavioral phenotypes of Disc1 missense mutations in mice" 54(3):387-402).

Figure 3. In spite of the lowered Acoustic Startle Response, Disc1-L100P mutants were able to distinguish wide range of sound intensities detected in Acoustic Startle Threshold (Clapcote et al. 2007. Neuron. "Behavioral phenotypes of Disc1 missense mutations in mice" 54(3):387-402).