Acoustic Startle Reflex and Prepulse Inhibition

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Abstract
Table of Contents
Materials
Figures
Literature Cited

Abstract

The completion of genome sequencing in humans and mice has opened new opportunities to study the relationship between gene expression and behavior and for development of novel therapeutic approaches for brain diseases. Recently, several international programs for large?scale production and phenotyping of genetically modified mice have been launched (e.g., EUCOMM, EUMODIC, IMPC), and comprehensive high?throughput behavioral phenotyping strategies have been developed (EUMORPHIA). In this context, startle reflex represents an important research tool for studying the impact of genetic manipulations not only on sensory processes but also on complex brain functions such as cognition, emotions, and movement control. In this unit, step?by?step protocols for measurement of acoustic startle reactivity and prepulse inhibition of startle in mice are described, and supporting experimental data presented. Curr. Protoc. Mouse Biol. 2:25?35 © 2012 by John Wiley & Sons, Inc.

Keywords: startle reactivity; prepulse inhibition; anxiety; auditory function; neuropsychiatric diseases

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Introduction
Basic Protocol 1: Acoustic Startle Reactivity
Basic Protocol 2: Acoustic Prepulse Inhibition
Support Protocol 1: Calibration Procedure for SR Lab System
Commentary
Literature Cited
Figures

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Materials

Basic Protocol 1: Acoustic Startle Reactivity

Materials

Mice of desired strain, gender and genotype, depending on the objective of the study
50% ethanol in tap water

SR Lab system (San Diego Instruments, http://www.sandiegoinstruments.com/ also see protocol 3 ).
Sound pressure level meter
Movement calibration unit

NOTE: The calibration of the stimuli used and the movement sensors are fundamental in obtaining accurate test results. These parameters must be calibrated before each experiment. Since both largely depend on the type of equipment used, the manufacturer's instructions for calibration must be followed rigorously (see protocol 3 for an example using the SR Lab System).

Basic Protocol 2: Acoustic Prepulse Inhibition

Materials

Mice of desired strain, gender and genotype, depending on the objective of the study
50% ethanol in tap water

Startle device (see above and see Basic Protocol)
Sound pressure level meter
Movement calibration unit
Lux‐meter in case of evaluation of visual PPI

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Figures

Figure 1. Pre‐exposure to social stress (social crowding), increased anxiety, and acoustic startle reactivity in C57BL/6J (B6), but not in Balb/cBYJ (CBy) mice. Left panels: Acoustic startle reactivity of mice housed individually (IH) or in crowded conditions (SolCr: 7 mice per cage) to 40‐msec‐long white‐noise bursts of increasing intensities (75 to 120 dB). BN: background noise (65‐dB). Right panels: Anxiety‐related behavior was measured in the elevated plus maze, where mice are confronted with a threatening environment composed of open arms and a safe enclosure. Percentage of time in the open arms is used as index of anxiety; lower percentage reflects increased anxiety. Results are expressed as mean ±SEM * p < 0.05 versus individually housed counterparts (Fisher's PLSD test). Redrawn from Reiss et al. () with permission.

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Figure 2. Startle reactivity and auditory brain stem (ABR) threshold in C57BL/6J (B6), 129S2/SvPas (129), and F1‐hybrids with age. Left panels: Startle reflex responses of mice to acoustic pulses (75 to 120 dB) at: 6 weeks, 41 weeks, and 94 weeks of age ( n = 8 to 11 mice per strain). Acoustic stimuli were 40 msec long and presented 10 times in random order. BN: activity during 65‐dB background noise. Right panels: ABR thresholds were measured at 6 weeks, 41 weeks, and 94 weeks of age. At 6 weeks, differences in the high‐frequency region of the ABR threshold curve are already visible between the three mouse strains. The differences become more and more obvious in older mice and extend to all frequencies. The hybrids present relatively stable ABR thresholds with age, whereas C57 mice show the most important ABR threshold shift followed by 129 mice. The dashed line represents the maximum output of our set up. Data are expressed as mean ± SEM. Redrawn from Ouagazzal et al. () with permission.

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Figure 3. Across‐laboratory evaluation of prepulse inhibition of the acoustic startle in four inbred strains: C57BL/6J, C3HeB/FeJ, Balb/cBYJ, and 129S2/SvPas. Inter‐strain differences in PPI (C57=BALB<C3H<129) were consistent between laboratories. Data are expressed as mean ±SEM; * p < 0.05 versus B6 and Balb, ^# p <0.05, versus all strains (Fischer's PLSD test). Redrawn from Mandillo et al. () with permission.

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Literature Cited

Literature Cited
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