Mice lacking paternal expression of imprintedGrb10are risk-takers

Abstract

22The imprinted genes Grb10 and Nesp influence impulsive behavior on a delay discounting 23 task in an opposite manner. A recently developed theory suggests that this pattern of 24 behavior may be representative of predicted effects of imprinted genes on tolerance to risk. 25Here we examine whether mice lacking paternal expression of Grb10 show abnormal 26 behavior across a number of measures indicative of risk-taking. Although Grb10 +/p mice 27 show no difference from wild type littermates in their willingness to explore a novel 28 environment, their behavior on an explicit test of risk-taking, namely the Predator Odour 29Risk-Taking task, is indicative of an increased willingness to take risks. Follow-up tests 30 suggest that this risk-taking is not simply due to a general decrease in fear, or a general 31 increase in motivation for a food reward, but reflects a change in the trade-off between cost 32 and reward. These data, coupled with previous work on the impulsive behaviour of Grb10 +/p 33 mice in the delayed reinforcement task, and taken together with our work on mice lacking 34 maternal Nesp, suggest that maternally and paternally expressed imprinted genes oppositely 35 influence risk-taking behaviour as predicted. 36

Mice carrying paternal knockout of imprintedGrb10do not show compulsive behaviour

“…However, behaviour on the EPM was altered, with Grb10 +/p mice being more willing to enter, spending more time on, and making more head-dips on the open arm than wild-type litter mates. Taken together with previous findings (Dent et al, 2020; Dent et al, 2018), we suggest these data provide further support for the idea that Grb10 +/p mice are more willing to take risks.…”

“…Grb10 +/p mice showed no evidence of abnormal compulsive behaviours, discounting this explanation of altered allogrooming behaviour. However, auxiliary measures on the EPM support previous evidence suggesting Grb10 +/p mice are more willing to take risk (Dent et al, 2020). The increased whisker barbering phenotype seen in Grb10 +/p mice has been suggested to indicate an increased compulsive behavioural phenotype rather than being indicative of altered social behaviour (Curley, 2011;Haig & Úbeda, 2011;and comment online on Garfield et al, 2011).…”

“…Grb10 +/p mice showed increased total arm, closed arm, and middle zone entries, as well as increased velocity compared to wildtype cage mates (entries to the open arm were not different (Rienecker et al, 2019)). This behaviour is curious because Grb10 +/p mice showed no differences in long (1-3 days) or short (5 min bins over 120 min) duration locomotor activity assessments, nor any differences in the novel place preference (NPP) test (Dent et al, 2020). Increased zone entries and velocity in the EPM may not be explained by generally increased locomotion, nor enhanced exploration of a novel environment.…”

“…We have previously shown that Grb10 +/p mice are more tolerant of risk in the delayed reinforcement task (DRT) and the predator odour risk-taking (PORT) task (Dent et al, 2018(Dent et al, , 2020, matching theoretical predictions that imprinted genes regulate risk tolerance (Wilkins & Bhattacharya, 2018). Unlike in the DRT and PORT, where risk-taking is related to a loss of opportunity and/or risk of predation while waiting for or pursuing a food reward, head dipping on the EPM is a risk related to directed exploration of an novel environment with no prior expectation of reward.…”

“…Imprinted genes, defined by their parent-of-origin specific epigenetic marks and monoallelic expression, are highly expressed in the brain and linked to behaviour. Paternal expression of imprinted Grb10 is prominent in monoaminergic regions of the midbrain and influences a range of behaviours (Dent et al, 2020; Dent et al, 2018; Garfield et al, 2011). In particular, Grb10 paternal knockout mice ( Grb10 +/p ) mice have an enhanced allogrooming phenotype (Garfield et al, 2011) which has been inferred to indicate social dominance, but could also index compulsive behaviour (Haig and Ubeda, 2011).…”