Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1

Abstract

Differential gene expression within the identified linkage region in highly-impulsive rats. To identify potential candidate genes within the linkage region we conducted a microarray analysis to investigate differences in transcript levels between HI and LI from both the outbred base population and animals from the sixth generation of the pedigree to identify common alterations in transcriptome expression associated with impulsivity. We investigated transcript expression in the NAcC, NAcS and in the case of sixth generation rats, the ventromedial PFC, or infralimbic cortex (IL) (Fig. 4A). Of the 148 genes within the linkage region represented on the array (Supplementary Table S5), several of these genes were found to be differentially-regulated in HI and LI rats (false discovery rate 10%) based on a non-parametric ranking analysis of the microarray data. A total of 13 transcripts were found to be up-regulated and 16 down-regulated in HI rats of the outbred base population, while 6 transcripts were up-regulated and 7 down-regulated in the F6 generation of HI rats (Table 2). Of these differentially-expressed transcripts, two were found to be consistently differentially-regulated in the same direction, in the same brain region between the two generations examined, Hbb and Nmb (Fig. 4B). After integration of the differential expression findings with the WGS results, we found that some of the differentially-expressed genes were also polymorphic (Pde3b, Sv2b, and Hbb; Supplementary Table S3) or had indels (Sv2b,

Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel

“…This supports previous findings in both human and animal literature that impulsivity is a heritable trait. Heritability estimates for premature responding reported here are greater than past estimates derived from measures of response to selection in outbred rats 76 . Delay discounting heritability estimates are on par with estimates that have been reported previously for inbred mice populations, 42,77 while estimates for behavioral flexibility in reversal learning are lower than what has been reported in inbred BXD mice 36 .…”

Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel

“…This supports previous findings in both human and animal literature that impulsivity is a heritable trait. Heritability estimates for premature responding reported here are greater than past estimates derived from measures of response to selection in outbred rats (Jupp et al, 2020).…”

Assessing Impulsivity in Humans and Rodents: Taking the Translational Road

“…For instance, impulsivity has been reported as sex dependent in both humans ( Cross et al, 2011 ; Weafer and de Wit, 2014 ) and rodents ( Weafer and de Wit, 2014 ; Soares et al, 2018 ), but the direction and strength of such effect depend on the assessed dimension. Additional variability may arise due to the mediation of other factors, as hormonal cycle in women ( Diekhof, 2015 ) and female rats ( Swalve et al, 2016 ), age ( Soares et al, 2018 , rats; Rosenbaum and Hartley, 2019 , humans), genetics ( Bezdjian et al, 2011 , humans; Soares et al, 2018 , rats; Jupp et al, 2020 , rats), or environment ( Bezdjian et al, 2011 , humans; Kirkpatrick et al, 2013 , rats). These influences, as well as their human–rodent parallels, are of high importance for the development of translational research.…”