Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Owen, Elizabeth H.; Christensen, Steven C.; Paylor, Richard; Wehner, Jeanne M.

doi:10.1037/0735-7044.111.2.292

Cited by 63 publications

(59 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A relatively greater correlation for cued conditioning is in agreement with evidence from lesion studies demonstrating the importance of the BLA for cued relative to contextual fear conditioning, the latter involving greater recruitment of additional structures, notably the hippocampus (Maren and Quirk, 2004). These data also concur with gene-mapping studies in BXD RIs indicating that cued and contextual conditioning are under partly dissociable genetic control (Owen et al, 1997;Wehner et al, 1997). Finally, the fact that we were able to detect two correlating phenotypic traits (BLA volume and fear memory) across two laboratories (University of Tennessee, NIH) speaks both to the strength and replicability of the underlying genetic component (Wahlsten et al, 2006).…”

Section: Discussionsupporting

confidence: 80%

“…BXD RI mice are inbred strains derived from C57BL/6 and DBA/2 (Taylor, 1978;Chesler et al, 2003) that have been used to identify chromosomal loci underlying fear-and anxiety-related phenotypes (Caldarone et al, 1997;Owen et al, 1997;Wehner et al, 1997;Valentinuzzi et al, 1998), as well as volume and cell number variation in various brain regions (Neumann et al, 1993;Airey et al, 2001Airey et al, , 2002Lu et al, 2001;Rosen and Williams, 2001;Williams et al, 2001;Seecharan et al, 2003). We selected 17 BXD RI lines and assigned them to subgroups with relatively small, medium, and large BLA volume.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Yang

Mozhui

Karlsson

et al. 2008

Neuropsychopharmacol

131

106

View full text Add to dashboard Cite

A wealth of research identifies the amygdala as a key brain region mediating negative affect, and implicates amygdala dysfunction in the pathophysiology of anxiety disorders. Although there is a strong genetic component to anxiety disorders such as posttraumatic stress disorder (PTSD) there remains debate about whether abnormalities in amygdala function predispose to these disorders. In the present study, groups of C57BL/6 Â DBA/2 (B Â D) recombinant inbred strains of mice were selected for differences in volume of the basolateral amygdala complex (BLA). Strains with relatively small, medium, or large BLA volumes were compared for Pavlovian fear learning and memory, anxiety-related behaviors, depression-related behavior, and glucocorticoid responses to stress. Strains with relatively small BLA exhibited stronger conditioned fear responses to both auditory tone and contextual stimuli, as compared to groups with larger BLA. The small BLA group also showed significantly greater corticosterone responses to stress than the larger BLA groups. BLA volume did not predict clear differences in measures of anxiety-like behavior or depression-related behavior, other than greater locomotor inhibition to novelty in strains with smaller BLA. Neither striatal, hippocampal nor cerebellar volumes correlated significantly with any behavioral measure. The present data demonstrate a phenotype of enhanced fear conditioning and exaggerated glucocorticoid responses to stress associated with small BLA volume. This profile is reminiscent of the increased fear processing and stress reactivity that is associated with amygdala excitability and reduced amygdala volume in humans carrying loss of function polymorphisms in the serotonin transporter and monoamine oxidase A genes. Our study provides a unique example of how natural variation in amygdala volume associates with specific fear-and stress-related phenotypes in rodents, and further supports the role of amygdala dysfunction in anxiety disorders such as PTSD.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Yang

Mozhui

Karlsson

et al. 2008

Neuropsychopharmacol

131

106

View full text Add to dashboard Cite

show abstract

“…This observation confirms that this trait is governed by a gene or genes linked to Il10 and not by an unlinked contaminant. These findings agree with several previous studies that map QTLs for emotionality to this region (Flint et al 1995;Caldarone et al 1997;Owen et al 1997a;Wehner et al 1997;Talbot et al 1999;Turri et al 1999;Koyer et al 2000). In a recent paper, Talbot et al (1999) …”

Section: Resultssupporting

confidence: 83%

Mapping of Quantitative Trait Loci with Knockout/Congenic Strains

Bolivar¹,

Cook²,

Flaherty³

2001

Genome Res.

View full text Add to dashboard Cite

Recently we have explored the use of knockout/congenic mouse strains for isolating and mapping quantitative trait loci (QTLs). Because most knockout strains have been bred to be B6.129 congenic strains, they can be used to test for QTLs in the targeted chromosomal area as long as there is a genetic difference between B6 and 129. Thus, we have tested a number of knockout/congenic strains in a series of behavioral tests in which mouse performance has a significant genetic component. We have also developed a breeding scheme for distinguishing the effects of background flanking genes from the targeted ablation. In screening several knockout/congenics, we have found at least one that harbors a behavioral QTL in the 129 chromosomal segment. The position of this QTL was confirmed subsequently by several F1 crosses.Mice with ablations of single genes have been extremely useful in analyzing gene function. They have revolutionized our ability to test new hypotheses about the nature of human diseases, especially ones that are caused by genetic mutations. However, because of the way that these strains are generally derived, they also can be used to map complex traits. In essence, many established knockout mice are also congenic strains that have retained a short piece of 129 genetic material surrounding the target ablated locus. Commonly, when knockout mice are made, embryonic stem cells derived from the 129 strain of mice are used. Once these stem cells become germline, the mice are routinely backcrossed to the B6 strain for a number of generations (usually 6-10). This backcrossing scheme yields a congenic strain in which most background genes are derived from B6 but the chromosomal segment flanking the target gene remains of 129 origin. There are >50 of these knockout/congenic strains commercially available. Thus, these knockout/congenic strains represent a potential resource for mapping genes surrounding the target (or knocked out) locus. To investigate this resource, we have used these strains to map genes affecting certain behaviors, including open field activity. We selected open field activity as it has successfully been used as a measure of exploratory behavior and emotionality in mice (Flint et al. 1995;Koyer et al. 2000). The positions of any potential QTLs were then confirmed by additional crosses. RESULTSWe have tested a number of knockout/congenic mouse strains in hopes of detecting background flanking 129 genes that affect behavioral characteristics. In past studies, we have found that the 129S1/SvImJ (129) strain performs differently from C57BL/6J (B6) on a variety of behavioral tests (Bolivar et al. 2000a;Cook et al. 2001; Bolivar et al., in press). Others have found differences between 129 and B6 strains as well (Logue et al. 1997;Owen et al. 1997b;Balogh et al. 1999;Paulus et al. 1999;Tarantino et al. 2000). This evidence supports our search for 129-derived chromosomal regions that may influence behavioral phenotypes. Although the 129 source of embryonic stem cells in many of the knockouts may be from a di...

show abstract

“…Two of these studies (Owen et al 1997b;Choy et al 2012) preexposed the mice to the training context prior to testing. Pre-exposure has been shown to alter later freezing responses to the context (Paylor et al 1994), and interestingly, pre-exposure prior to training is one of the only differences between Owen et al (1997b), in which no context difference was observed, and Owen et al (1997a), in which a significant difference was reported. Choy et al (2012) gave saline injections to their D2 mice, but not their B6 mice, suggesting that the stress of injection could have increased the level of D2 freezing.…”

Section: Context Freezingmentioning

confidence: 99%

Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance

et al. 2014

View full text Add to dashboard Cite

Strain comparison studies have been critical to the identification of novel genetic and molecular mechanisms in learning and memory. However, even within a single learning paradigm, the behavioral data for the same strain can vary greatly, making it difficult to form meaningful conclusions at both the behavioral and cellular level. In fear conditioning, there is a high level of variability across reports, especially regarding responses to the conditioned stimulus (CS). Here, we compare C57BL/6 and DBA/2 mice using delay fear conditioning, trace fear conditioning, and a nonassociative condition. Our data highlight both the significant strain differences apparent in these fear conditioning paradigms and the significant differences in conditioning type within each strain. We then compare our data to an extensive literature review of delay and trace fear conditioning in these two strains. Finally, we apply a number of commonly used baseline normalization approaches to compare how they alter the reported differences. Our findings highlight three major sources of variability in the fear conditioning literature: CS duration, number of CS presentations, and data normalization to baseline measures.

show abstract

Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Cited by 63 publications

References 26 publications

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Mapping of Quantitative Trait Loci with Knockout/Congenic Strains

Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance

Contact Info

Product

Resources

About