Maternal and Genetic Effects on the Acoustic Startle Reflex and its Sensitization in C3H/HeN, DBA/2JHd and NMRI Mice Following Blastocyst Transfer

Abstract

In the present study, reciprocal embryo transfers were conducted to examine genetic and maternal effects on the baseline and fear-sensitized acoustic startle response (ASR) in the two inbred strains C3H/HeN and DBA/2JHd and the outbred strain NMRI. The largest differences in the ASR were found in untreated strains (effect size 0.6). The transfer procedure per se had a significant effect on the behavior of NMRI mice resulting in a reduction in the baseline, and an increase in the fear-sensitized ASR. In contrast, there were no significant effects of the transfer procedure in the two inbred strains. Autosomal genetic effects had a stronger impact on the amplitude of the ASR (effect sizes 0.5) than sex (effect sizes 0.06) as revealed by reciprocal embryo transfer. Nevertheless, the genetic effects on the fear-sensitized ASR were somewhat more variable and strain-dependent (effect sizes 0.1-0.2). Global maternal effects were detected after embryo transfer into NMRI mothers resulting in a larger reduction of the ASR in the offspring of DBA and NMRI donors than C3H donors (effect sizes 0.1-0.2). An additional fostering procedure was introduced to dissect uterine and postnatal maternal effects in NMRI offspring. Uterine factors changed the baseline ASR of the offspring in direction of the recipient mother strain. Surprisingly, postnatal maternal effects on the ASR were contrary to the behavior of the rearing mother. In conclusion, both genetic and prenatal/postnatal maternal factors persistently influenced the ASR of the offspring, whereas the fear-sensitized ASR was mainly influenced by genetic factors. Our study shows that uterine and postnatal maternal influences deserve more attention when determining the phenotype of genetically engineered mice at least in the first generation following embryo transfer.

Serotonin1A receptor deletion does not interact with maternal separation-induced increases in startle reactivity and prepulse inhibition deficits

“…This observation is in line with a study comparing maternal and genetic effects using different mouse strains. It was shown that foot shock sensitization is mainly influenced by genetic factors, whereas startle reactivity is affected both by genetic and prenatal and postnatal factors (Rose et al 2008). Accordingly, mouse strains may differ in the magnitude of the response and also in the time frame in which the shock sensitization occurs (Dirks et al 2001a), as was also found in the present study.…”

“…It is well known that mouse strains vary widely in their emotional reactivity (Bothe et al 2005; Crawley et al 1997; van Bogaert et al 2006), as well as in startle reactivity (Pietropaolo and Crusio 2009; Rose et al 2008) and PPI (Millstein et al 2006; Paylor and Crawley 1997). In the present study, comparable strain differences were observed.…”

Acoustic startle modification as a tool for evaluating auditory function of the mouse: Progress, pitfalls, and potential

“…If the prepulse is temporally coupled with an aversive stimulus for a number of times, increased ASR amplitude and reduced PPI have been observed (Davis et al 1993, Falls et al 1997, Heldt et al 2000; McCaughran et al 2000; Dirks et al 2001; Balogh et al 2002; Rose et al 2008; Li et al 2009). It is a common observation that ASR, PPI, and how the modification of the response changes over time differs between mouse strains and individuals of the same strain (e.g., Bullock et al 1997; Pilz et al 2004; Simons-Weidenmaier et al 2006; Typlt et al 2013a Yee et al 2005, and see section 4.1 Strain).…”

“…Variables such as maternal separation, rearing, and other social effects may influence the expression of ASR and PPI (Francis et al 2003; Millstein et al 2006; Rose et al 2008). Social isolation produces PPI deficits in at least four strains of mice (C57BL6/J and 129T2-Varty et al 2006; ddY-Sakaue et al 2003; C57BL/6-Pietropaolo et al 2008; C57BL6/J-Martin and Brown 2010).…”

Genetics and Cognition

“…Two methods have been used with mice: embryo transfers (Denenberg, Hopligh, & Mobraaten, 1998) and grafted ovaries (Carlier, Roubertoux, & Pastoret, 1991), both in conjunction with the adoption method. In short, many studies conducted on rodents concluded that genetic variation is linked to differences in a large range of behavioral traits, including learning, in conjunction or interaction with the maternal environment (Carlier et al, 1992, 1999 – see Rose, Röhl, Hanke, Schwegler, & Yilmazer-Hanke, 2008 for recent examples.…”