The effects of Eph-ephrin mutations on pre-pulse inhibition in mice

Abstract Eph–ephrin signaling is known to be important in directing topographic projections in the afferent auditory pathway, including connections to various subdivisions of the inferior colliculus (IC). The acoustic startle-response (ASR) is a reliable reflexive behavioral response in mammals elicited by an unexpected intense acoustic startle-eliciting stimulus (ES). It is mediated by a sub-cortical pathway that includes the IC. The ASR amplitude can be measured with an accelerometer under the subject and can be decreased in amplitude by presenting a less intense, non-startling stimulus 5–300 ms before the ES. This reflexive decrement in ASR is called pre-pulse inhibition (PPI) and indicates that the relatively soft pre-pulse was heard. PPI is a general trait among mammals. Mice have been used recently to study this response and to reveal how genetic mutations affect neural circuits and hence the ASR and PPI. In this experiment, we measured the effect of Eph–ephrin mutations using control mice (C57BL/6 J), mice with compromised EphA4 signaling (EphA4 lacZ /+ , EphA4 lacZ / lacZ ), and knockout ephrin-B3 mice (ephrin-B3 +/−, −/− ). Control and EphA4 lacZ /+  s trains showed robust PPI (up to 75% decrement in ASR) to an offset of a 70 dB SPL background noise at 50 ms before the ES. Ephrin-B3 knockout mice and EphA4 homozygous mutants were only marginally significant in PPI (