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  • 1.
    Brunberg, E.
    et al.
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Isaksson, A.
    Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Keeling, L.J.
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Brain gene expression differences are associated with abnormal tail biting behavior in pigs2013In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 12, no 2, p. 275-281Article in journal (Refereed)
    Abstract [en]

    Knowledge about gene expression in animals involved inabnormal behaviors can contribute to the understandingof underlying biological mechanisms. This study aimedto explore the motivational background to tail biting,an abnormal injurious behavior and severe welfareproblem in pig production. Affymetrix microarrayswere used to investigate gene expression differencesin the hypothalamus and prefrontal cortex of pigsperforming tail biting, pigs receiving bites to the tailand neutral pigs who were not involved in the behavior.In the hypothalamus, 32 transcripts were differentiallyexpressed (P <0.05) when tail biters were comparedwith neutral pigs, 130 when comparing receiver pigswith neutrals, and two when tail biters were comparedwith receivers. In the prefrontal cortex, seven transcriptswere differently expressed in tail biters when comparedwith neutrals, seven in receivers vs. neutrals and nonein the tail biters vs. receivers. In total, 19 genesshowed a different expression pattern in neutral pigswhen compared with both performers and receivers.This implies that the functions of these may provideknowledge about why the neutral pigs are not involvedin tail biting behavior as performers or receivers.Among these 19 transcripts were genes associated withproduction traits in pigs (PDK4), sociality in humansand mice (GTF2I ) and novelty seeking in humans (EGF ).These are in line with hypotheses linking tail biting withreduced back fat thickness and explorative behavior.

  • 2.
    Granseth, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Fredrik K
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Sarah H
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1)2015In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 14, no 6, p. 477-485Article in journal (Refereed)
    Abstract [en]

    Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinsons disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (PFC) show similar rigidity, owing to the loss of PFC regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (VGluT1) is preferentially expressed at modulatory synapses, including PFC neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). VGluT1(+/-) mice display behavioral phenotypes matching many symptoms of schizophrenia, and VGluT1 expression is reduced in the PFC of patients with schizophrenia and Parkinsons disease. Thus, it appears likely that VGluT1-expressing synapses from PFC play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in VGluT1(+/-) mice by testing reversal learning in a visual discrimination task. Here, we show that VGluT1(+/-) mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from PFC, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.

  • 3.
    Heilig, Markus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Barbier, Estelle
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience.
    Johnstone, A. L.
    University of Miami, FL 33136 USA.
    Tapocik, J.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Meinhardt, M. W.
    Heidelberg University, Germany.
    Pfarr, S.
    Heidelberg University, Germany.
    Wahlestedt, C.
    University of Miami, FL 33136 USA.
    Sommer, W. H.
    Heidelberg University, Germany.
    Reprogramming of mPFC transcriptome and function in alcohol dependence2017In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 16, no 1, p. 86-100Article, review/survey (Refereed)
    Abstract [en]

    Despite its limited immediate reinforcement value, alcohol has a potent ability to induce neuroadaptations that promote its incentive salience, escalation of voluntary alcohol intake and aversion-resistant alcohol seeking. A constellation of these traits, collectively called post-dependent, emerges following brain exposure to repeated cycles of intoxication and withdrawal. The medial prefrontal cortex (mPFC) and its subdivisions exert top-down regulation of approach and avoidance behaviors, including those that lead to alcohol intake. Here, we review an emerging literature which indicates that a reprogramming of mPFC function occurs with prolonged exposure of the brain to cycles of alcohol intoxication and withdrawal. This reprogramming results in molecular dysregulations that contribute to the post-dependent syndrome. Convergent evidence has identified neuroadaptations resulting in altered glutamatergic and BDNF-mediated signaling, and for these pathways, direct evidence for a mechanistic role has been obtained. Additional evidence points to a dysregulation of pathways involving calcium homeostasis and neurotransmitter release. Recent findings indicate that global DNA hypermethylation is a key factor in reprogramming the mPFC genome after a history of dependence. As one of the results of this epigenetic remodeling, several histone modifying epigenetic enzymes are repressed. Among these, PR-domain zinc-finger protein 2, a methyltransferase that selectively mono-methylates histone H3 at lysine 9 has been functionally validated to drive several of the molecular and behavioral long-term consequences of alcohol dependence. Information processing within the mPFC involves formation of dynamic neuronal networks, or functional ensembles that are shaped by transcriptional responses. The epigenetic dysregulations identified by our molecular studies are likely to alter this dynamic processing in multiple ways. In summary, epigenetic molecular switches in the mPFC appear to be turned on as alcoholism develops. Strategies to reverse these processes may offer targets for disease-modifying treatments.

  • 4.
    Jöngren, Markus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Westander, Jennie
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Nätt, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Brain gene expression in relation to fearfulness in female red junglefowl (Gallus gallus)2010In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 9, no 7, p. 751-758Article in journal (Refereed)
    Abstract [en]

    The biology of fear is central to animal welfare and hasbeen a major target for selection during domestication.Fear responses were studied in female red junglefowl(RJF), the ancestor of domesticated chickens. A totalof 31 females were tested in a ground predator test,an aerial predator test and a tonic immobility (TI)test, in order to assess their level of fearfulnessacross different situations. Two to six variables fromeach test were entered into a principal component(PC) analysis, which showed one major fearfulnesscomponent (explaining 27% of the variance). Based onthe PC scores, four high- and four low-fearful birds werethen selected for gene expression analysis. From eachof these birds, the midbrain region (including thalamus,hypothalamus, pituitary, mesencephalon, pons, nucleustractus solitarii and medulla oblongata), was collectedand global gene expression compared between groupsusing a 14k chicken cDNA microarray. There were 13significantly differentially expressed (DE) genes (basedonM > 1 andB > 0; FDR-adjusted P < 0.05) between thefearful and non-fearful females. Among the DE genes,we identified the neuroprotein Axin1, two potentialDNA/RNA regulating proteins and a retrotransposontranscript situated in a well-studied quantitative traitloci (QTL) region on chromosome 1, known to affectseveral domestication-related traits. The differentiallyexpressed genes may be part of a possible molecularmechanism controlling fear responses in fowl.

  • 5.
    Katajamaa, Rebecca
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Tameness correlates with domestication related traits in a Red Junglefowl intercross2021In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 20, no 3, article id e12704Article in journal (Refereed)
    Abstract [en]

    Early animal domestication may have been driven by selection on tameness. Selection on only tameness can bring about correlated selection responses in other traits, not intentionally selected upon, which may be one cause of the domesticated phenotype. We predicted that genetically reduced fear towards humans in Red Junglefowl, ancestors of domesticated chickens, would be correlated to other traits included in the domesticated phenotype. Fear level was determined by a standardised behaviour test, where the reaction towards an approaching human was recorded. We first selected birds for eight generations for either high or low fear levels in this test, to create two divergent selection lines. An F3 intercross, with birds from the eighth generation as parentals, was generated to study correlations between fear-of-human scores and other unselected phenotypes, possibly caused by pleiotropy or linkage. Low fear-of-human scores were associated with higher body weight and growth rates, and with increased activity in an open field test, indicating less general fearfulness. In females, low fear-of-human scores were also associated with more efficient fear habituation and in males with an increased tendency to emit food calls in a mirror test, indicating increased social dominance. Low fear-of-human scores were also associated with smaller brain relative to body weight, and with larger cerebrum relative to total brain weight in females. All these effects are in line with the changes observed in domesticated chickens compared to their ancestors, and we conclude that tameness may have been a driving factor underlying some aspects of the domesticated phenotype.

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  • 6.
    Persson, Mia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Roth, Lina
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Human-directed social behaviour in dogs shows significant heritability2015In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 14, no 4, p. 337-344Article in journal (Refereed)
    Abstract [en]

    Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h2) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs’ social skills, which could also play a significant part into research on human social disorders such as autism.

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  • 7.
    Sundman, Ann-Sofie
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Similar recent selection criteria associated with different behavioural effects in two dog breeds2016In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 15, no 8, p. 750-756Article in journal (Refereed)
    Abstract [en]

    Selection during the last decades has split some established dog breeds into morphologically and behaviourally divergent types. These breed splits are interesting models for behaviour genetics since selection has often been for few and well-defined behavioural traits. The aim of this study was to explore behavioural differences between selection lines in golden and Labrador retriever, in both of which a split between a common type (pet and conformation) and a field type (hunting) has occurred. We hypothesized that the behavioural profiles of the types would be similar in both breeds. Pedigree data and results from a standardized behavioural test from 902 goldens (698 common and 204 field) and 1672 Labradors (1023 and 649) were analysed. Principal component analysis revealed six behavioural components: curiosity, play interest, chase proneness, social curiosity, social greeting and threat display. Breed and type affected all components, but interestingly there was an interaction between breed and type for most components. For example, in Labradors the common type had higher curiosity than the field type (F1,1668 = 18.359; P < 0.001), while the opposite was found in goldens (F1,897 = 65.201; P < 0.001). Heritability estimates showed considerable genetic contributions to the behavioural variations in both breeds, but different heritabilities between the types within breeds was also found, suggesting different selection pressures. In conclusion, in spite of similar genetic origin and similar recent selection criteria, types behave differently in the breeds. This suggests that the genetic architecture related to behaviour differs between the breeds.

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  • 8.
    Wirén, Anders
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Domestication-related variation in social preferences in chickens is affected by genotype on a growth QTL2013In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 12, no 3, p. 330-337Article in journal (Refereed)
    Abstract [en]

    A growth-related QTL on chicken chromosome 1 has previously been shown to influence domestication behaviour in chickens. In this study, we used Red Junglefowl (RJF) and White Leghorn (WL) as well as the intercross between them to investigate whether stress affects the way birds allocate their time between familiar and unfamiliar conspecifics in a social preference test (‘social support seeking’), and how this is related to genotype at specific loci within the growth QTL. Red Junglefowl males spent more time with unfamiliar chickens before the stressful event compared to the other birds, whereas all birds except WL males tended to spend less time with unfamiliar ones after stress. A significant QTL locus was found to influence both social preference under undisturbed circumstances and social support seeking. The WL allele at this QTL was associated not only with a preference for unfamiliar individuals but also with a shift towards familiar ones in response to stress (social support seeking). A second, suggestive QTL also affected social support seeking, but in the opposite direction; the WL allele was associated with increased time spent with unfamiliar individuals. The region contains several possible candidate genes, and gene expression analysis of a number of them showed differential expression between RJF and WL of AVPR2 (receptor for vasotocin), and possibly AVPR1a (another vasotocin receptor) and NRCAM (involved in neural development) in the lower frontal lobes of the brains of RJF and WL animals. These three genes continue to be interesting candidates for the observed behavioural effects.

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