Unique genetic loci identified for emotional behavior in control and chronic stress conditions

Abstract

An individual's genetic background affects their emotional behavior and response to stress. Although studies have been conducted to identify genetic predictors for emotional behavior or stress response, it remains unknown how prior stress history alters the interaction between an individual's genome and their emotional behavior. Therefore, the purpose of this study is to identify chromosomal regions that affect emotional behavior and are sensitive to stress exposure. We utilized the BXD behavioral genetics mouse model to identify chromosomal regions that predict fear learning and emotional behavior following exposure to a control or chronic stress environment. 62 BXD recombinant inbred strains and C57BL/6 and DBA/2 parental strains underwent behavioral testing including a classical fear conditioning paradigm and the elevated plus maze. Distinct quantitative trait loci (QTLs) were identified for emotional learning, anxiety and locomotion in control and chronic stress populations. Candidate genes, including those with already known functions in learning and stress were found to reside within the identified QTLs. Our data suggest that chronic stress history reveals novel genetic predictors of emotional behavior.

Quantitative trait locus mapping and analysis of heritable variation in affiliative social behavior and co‐occurring traits

“…Second, and more compelling, several of the loci identified for center time and center latency have been previously implicated in emotional regulation and anxiety. In particular, the center latency QTL on Chr 13 has been previously mapped by our laboratory and others for conditioned fear and anxiety . In addition, there is evidence that the center time QTL on distal Chr 12 is involved in emotional reactivity during fear learning .…”

“…In particular, the center latency QTL on Chr 13 has been previously mapped by our laboratory and others for conditioned fear and anxiety. 46,49,131 In addition, there is evidence that the center time QTL on distal Chr 12 is involved in emotional reactivity during fear learning. 49 Finally, the center time QTL on distal Chr 1 is near a "QTL hotspot" 94 identified repeatedly for neural and behavioral phenotypes including locomotor activity, [132][133][134] emotional behavior, 135,136 and cerebellar size.…”

Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice

“…Previous studies have evaluated whether any of the specific phenotypes mapped back to the location of the differentially expressed genes in their respective group (Bice et al, 2010, 2006; Carhuatanta, Shea, Herman, & Jankord, 2014; Cook et al, 2015; Overall et al, 2009; Palmer, Lessov-Schlaggar, Ponder, McKinnon, & Phillips, 2006; Porcu et al, 2011; Urquhart et al, 2016). However, in the present study, only one phenotype mapped back to the location of a gene that was correlated with it: Cnot6l from the RSE vs. NOE group.…”

Impact of Genetic Variation on Stress‐Related Ethanol Consumption

“…The BXDs are particularly amenable for GXE studies because individual genotypes (strains) can be resampled under many different conditions, and the analysis of trait heritability, and subsequent quantitative trait locus (QTL) mapping, can be improved by increasing both the number of genotypes and individuals of each genotype that are sampled. The BXD family has also been densely profiled for molecular, pharmacological, behavioral, and physiological traits, including alcohol intake (Fernandez et al., ; Gill et al., ; Phillips et al., ; Rodriguez et al., ), response to stress (Carhuatanta et al., ; Jung et al., ; Shea et al., ), and gene expression in numerous tissues, including brain regions. However, the genetics of alcohol intake in response to chronic stress has never been profiled in this, or any, model population.…”

“…Physiological and behavioral responses to chronic stress as applied in the CMS paradigm are strongly dependent on genetic background (Ibarguen‐Vargas et al., ), and behavioral changes produced by CMS can be reversed by antidepressants (for review, see Willner, ). Furthermore, variation in cognitive and emotional behavior in response to chronic variable stress is heritable among the BXDs (Carhuatanta et al., ; Jung et al., ; Shea et al., ). Here, we report changes in voluntary DID alcohol intake during and after chronic stress exposure.…”