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Significant alterations in glutamatergic neurotransmission have been reported in major depressive disorder (MDD) that could underlie psychiatric traits. Studies were mainly interested in synaptic dysfunction in the prefrontal cortex, a key structure involved in depressive-like behavior, however hippocampus has been shown to be important in MDD. As cognitive deficits such as hippocampus-memory process were observed in MDD, we investigated in a mild hypoglutamatergic model behaviors related to depression and memory, synaptic transmission parameters and glutamatergic state specifically in the hippocampus. We thus characterized these phenotypes in adult male mice partially depleted in glutaminase type 1 or GLS1 (GLS1 HET), the enzyme responsible for glutamate synthesis in neurons, that we previously characterized as displaying moderate lower levels of glutamate in brain. We showed that GLS1 mutant mice display AMPA-R-mediated response deficits after prolonged repetitive stimulation with electrophysiological recording and inability to sustain glutamate release by microdialysis experiments with no consequences on behavioral spatial learning performances. However, their ability to escape from unpleasant but repeated escapable condition was attenuated whereas they were more immobile in the unescapable situation in the FST during re-test. These results show that GLS1 mutant mice display moderate impairments of hippocampal glutamatergic neurotransmission and moderate changes in adaptive behaviors that have been shown to participate to the development of depressive-like state.

International audience; In wild vertebrates, conspicuousness often signals a high phenotypic quality and is therefore associated with fitness benefits (“the handicap principle hypothesis”). However, conspicuous individuals usually face a higher risk of predation because they are easier to detect. Therefore, conspicuous individuals are expected to modify their behavioural and their physio logical stress responses to limit the negative effect of their conspicuousness on survival. We examined the link between plumage coloration and the stress response in a bird species (the rock pigeon, Columbia livia) by comparing two groups of pigeons with different plumage characteristics: ‘blue-bar’ birds (lighter birds) and ‘checker’ birds (darker birds). Specifically, we measured several behavioural and physiological components of the stress response (breath rate, corticosterone, and tonic immobility). Although breath rate did not differ between ‘checker’ and ‘blue bar’ birds, the corticosterone stress response of ‘blue-bar’ birds was greater relative to that of ‘checker’ birds. Moreover, ‘checker’ birds were more likely to initiate tonic immobility relative to ‘blue bar’ birds. Therefore, this study suggests that the behavioural and physiological stress responses of wild birds may differ according to their plumage coloration. To conclude, our results suggest that plumage colorations may be functionally linked to specific behavioral and physiological sensitivities to stressors.

International audience; The gut microbiota is involved in host behaviour and memory in mammals. Consequently, it may also influence emotional behaviour and memory in birds. Quail from two genetic lines with different fearfulness (LTI: long tonic immobility, n = 37; STI: short tonic immobility, n = 32) were either or not supplemented with a probiotic (Pediococcus acidilactici) from hatching. Emotional reactivity was measured in a tonic immobility test (d6 and 7 of age) and two open-field tests (d13 to 15; d22 to 24). Memory was measured in a test rewarded with mealworms, where quail had to remember the cups previously visited (d34 to 36). Quail endured a 5-days stress period from days 17 to 21 to help revealing the potentially beneficial effect of the probiotic. As expected, STI quail were less fearful compared to the LTI quail (p < 0.05). Probiotic supplementation had no effect on most measures of emotional reactivity (p > 0.05), except in the tonic immobility test where supplemented STI quail had lower immobility duration (p = 0.0001). Regarding the memory test, the two lines had similar performances. Quail fed with probiotics made fewer errors (p = 0.040). There was no significant correlation between traits of emotional reactivity and of memory. In conclusion, the supplementation with Pediococcus acidilactici as a probiotic, affected a specific trait of emotional reactivity in STI quail, and improved memory in both lines, whichstrengthens the idea that the influence of gut microbiota on the host behaviour and memory seen in mammals is shared by birds.

Background As for other non-model species, genetic analyses in quail will benefit greatly from a higher marker density, now attainable thanks to the evolution of sequencing and genotyping technologies. Our objective was to obtain the first genome wide panel of Japanese quail SNP (Single Nucleotide Polymorphism) and to use it for the fine mapping of a QTL for a fear-related behaviour, namely tonic immobility, previously localized on Coturnix japonica chromosome 1. To this aim, two reduced representations of the genome were analysed through high-throughput 454 sequencing: AFLP (Amplified Fragment Length Polymorphism) fragments as representatives of genomic DNA, and EST (Expressed Sequence Tag) as representatives of the transcriptome. Results The sequencing runs produced 399,189 and 1,106,762 sequence reads from cDNA and genomic fragments, respectively. They covered over 434 Mb of sequence in total and allowed us to detect 17,433 putative SNP. Among them, 384 were used to genotype two Advanced Intercross Lines (AIL) obtained from three quail lines differing for duration of tonic immobility. Despite the absence of genotyping for founder individuals in the analysis, the previously identified candidate region on chromosome 1 was refined and led to the identification of a candidate gene. Conclusions These data confirm the efficiency of transcript and AFLP-sequencing for SNP discovery in a non-model species, and its application to the fine mapping of a complex trait. Our results reveal a significant association of duration of tonic immobility with a genomic region comprising the DMD (dystrophin) gene. Further characterization of this candidate gene is needed to decipher its putative role in tonic immobility in Coturnix.

International audience; Chronic stress is known to enhance mammals' emotional reactivity and alters several of their cognitive functions, especially spatial learning. Few studies have investigated such effects in birds. We investigated the impact of a two-week stress on Japanese quail's emotional reactivity and spatial learning. Quail is an avian model widely used in laboratory studies and for extrapolation of data to other poultry species. As sensitivity to chronic stress can be modulated by intrinsic factors, we tested juvenile female Japanese quail from three lines, two of them divergently selected on tonic immobility duration, an indicator of general fearfulness. The different emotional reactivity levels of quail belonging to these lines can be revealed by a large variety of tests. Half of the birds were submitted to repeated unpredictable aversive events for two weeks, whereas the other half were left undisturbed. After this procedure, two tests (open field and emergence tests) evaluated the emotional reactivity of treated and control quails. They were then trained in a T-maze for seven days and their spatial learning was tested. The chronic stress protocol had an impact on resting, preening and foraging in the home cage. As predicted, the emotional reactivity of treated quails, especially those selected for long tonic immobility duration, was higher. Our spatial learning data showed that the treatment enhanced acquisition but not memorization. However, intrinsic fearfulness did not seem to interact with the treatment in this test. According to an inverted U-shaped relationship between stress and cognition, chronic stress can improve the adaptability of birds to a stressful environment. We discussed the mechanisms possibly implied in the increase of emotional reactivity and spatial abilities.

International audience; We examined the interaction between early life stress and vulnerability to alcohol in female rats exposed to prenatal restraint stress (PRS rats). First we studied the impact of PRS on ethanol preference during adolescence. PRS slightly increased ethanol preference per se, but abolished the effect of social isolation on ethanol preference. We then studied the impact of PRS on short- and long-term responses to ethanol focusing on behavioral and neurochemical parameters related to depression/anxiety. PRS or unstressed adolescent female rats received 10% ethanol in the drinking water for 4 weeks from PND30 to PND60. At PND60, the immobility time in the forced-swim test did not differ between PRS and unstressed rats receiving water alone. Ethanol consumption had no effect in unstressed rats, but significantly reduced the immobility time in PRS rats. In contrast, a marked increase in the immobility time was seen after 5 weeks of ethanol withdrawal only in unstressed rats. Hippocampal levels of neuropeptide Y (NPY) and mGlu1a metabotropic glutamate receptors were increased at the end of ethanol treatment only in unstressed rats. Ethanol treatment had no effect on levels of corticotropin-releasing hormone (CRH) in the hippocampus, striatum, and prefrontal cortex of both groups of rats. After ethanol withdrawal, hippocampal levels of mGlu1 receptors were higher in unstressed rats, but lower in PRS rats, whereas NPY and CRH levels were similar in the two groups of rats. These data indicate that early life stress has a strong impact on the vulnerability and responsiveness to ethanol consumption during adolescence.

International audience; There is considerable variability in the susceptibility of individuals to the adverse effects of chronic stress. In humans and other mammals, individual traits such as high anxiety are proposed as a vulnerability factor for the development of stress-related disorders. In the present study, we tested whether a similar behavioural trait in birds, higher emotional reactivity, also favours the occurrence of chronic stress-related behavioural and physiological dysfunction. For this, lines of Japanese quail divergently selected for a typical fear response in birds, the duration of tonic immobility, were subjected to unpredictable aversive stimulation over 2 weeks. Previous studies demonstrate that the selection program modifies the general underlying emotionality of the birds rather than exerting its effect only on tonic immobility. Interestingly, only birds selected for their higher emotionality exhibited significantly enhanced latency to first step and decreased locomotor activity in the open-field test after exposure to chronic stress compared to non-stressed control birds. This effect of chronic stress was selective for the tested dimension of bird emotional reactivity because there was no observed effect on the tonic immobility response. Moreover, chronically stressed birds selected for their higher emotionality exhibited significantly decreased basal corticosterone levels, a physiological marker of stress. These findings show that chronic stress is associated with changes in emotional reactivity and related physiological markers in birds. They also highlight emotional reactivity as an important predisposing factor for the occurrence of the adverse effects of chronic stress in birds.

Chronic stress is known to induce long term alterations of emotional behaviours as well as cognitive performances leading thereby to welfare or husbandry problems. These stress-induced consequences are observed following long periods of stress lasting from several weeks to several years. The current study examined whether a shorter period of stress (one week) produced similar impairing effects. Two-week old Japanese quail were either submitted to a series of aversive events over consecutive 8 days, at unpredictable times each day (treated animals) or left undisturbed (controls). Following the treatment period, animals were weighed and basal as well as aversive events-induced levels of plasma corticosterone were quantified. Quail were also tested for emotional reactivity in three tests (the tonic immobility test, the hole-in-the-wall and novel object tests) and for spatial reference memory. Although there was no difference in corticosterone levels between the two groups, the treated animals had lower body weight than controls. Behavioural investigations after the treatment period did not reveal any difference between the groups in the three emotional reactivity tests. In the spatial task, treated quail displayed enhanced behavioural flexibility as revealed by their higher performances during the reversal phase of the task. The alteration of growth suggests that a short period of repetitive exposures to unpredictable aversive events can be perceived by quail as stressful. Such a stress period can improve spatial learning performances in quail supporting the critical role played by the duration of the stress period on cognitive performance. (C) 2010 Elsevier B.V. All rights reserved.

International audience; Two genotypes of Japanese quail have been divergently selected since the 1980s for long (LTI) or short (STI) duration of tonic immobility [Mills, A.D., Faure, J.M., 1991. Divergent selection for duration of tonic immobility and social reinstatement behavior in Japanese quail (Coturnix coturnix japonica) chicks. J. Comp. Psychol. 105(1), 25-38.], an unlearnt catatonic state characteristic of a behavioral fear response ([Jones, R.B., 1986. The tonic immobility reaction of the domestic fowl: a review. World's Poult. Sci. J. 42(1), 82-97.]; [Mills, A.D., Faure, J.M., 1991. Divergent selection for duration of tonic immobility and social reinstatement behavior in Japanese quail (Coturnix coturnix japonica) chicks. J. Comp. Psychol. 105(1), 25-38.]). The results of several behavioral tests conducted in LTI and STI quail have led to the conclusion that LTI quail are more fearful than STI quail [Faure, J.M., Mills, A.D., 1998. Improving the adaptability of animals by selection. In: Grandin, T. (Eds.), Genetics and the behavior of domestic animals. Academic Press, San Diego, pp. 235-264.]). However, few studies to date have focused on the Hypothalamic-Pituitary-Adrenal (HPA) axis response to stressful situations in LTI and STI quail, although the HPA axis is involved in fear responses [Siegel, H.S., 1971. Adrenals, Stress and the Environment. World's Poult. Sci. J. 27, 327-349.]. The corticosterone (CORT) response to various putatively stressful situations was therefore assessed in LTI and STI genotypes of quail in order to investigate their HPA axis reactivity to stress. Repeated induction of TI or 1 min manual restraint induced significant and comparable increases in CORT levels in both genotypes as a TI response. On the other hand, higher CORT responses were found in STI than in LTI quail when the manual restraint period lasted for 2 min or after restraint in a crush cage. Maximum CORT responses and genotype differences were maintained throughout the latter test even when it lasted for 120 min. Investigation of the CORT response to a single TI episode showed that CORT levels at the end of TI were negatively correlated with TI duration. Other experimental contexts consisting of isolation in a familiar or novel environment or the presentation of a novel object induced slight but significant and comparable increases in CORT response in both genotypes, whereas change of cagemates did not. In conclusion, the present findings indicate that differences in HPA axis response are observed between LTI and STI genotypes when quail are submitted to intense stressors, resulting in a high and prolonged CORT response. By contrast, plasma corticosterone concentrations do not differ between STI and LTI quail in response to stressful situations of lower intensity, which evoke responses limited in amplitude and duration. Genetic selection for divergent duration of TI has thus affected the HPA axis response to stress, and LTI and STI quail constitute an interesting model to investigate genetic variability of HPA axis activity in birds. More specifically, these genotypes of quail could be used to investigate the occurrence of functional differences at different levels of the HPA axis in order to explain the present findings. (c) 2007 Elsevier Inc. All rights reserved.

International audience; Exposure to fearful situations elicits behavioral and Hypothalamic-Pituitary-Ad renal (HPA) axis responses characteristic of the coping response of individual animals to counteract environmental challenges. The aim of this study was to investigate behavioral and corticotropic responses concomitantly following prolonged or repeated restraint stress by placing two genotypes of Japanese quail divergently selected for long (LTI) or short (STI) duration of tonic immobility (TI) in a crush cage. In our study, STI quail exhibited higher corticosterone (CORT) levels than LTI quail in response to prolonged restraint. STI quail struggled sooner and much more than LTI quail, and struggling behavior in STI quail progressively decreased during the course of restraint whereas LTI quail displayed very little struggling behavior in the crush cage. LTI quail are thus more likely to adopt a passive behavior coping strategy upon exposure to threat whereas STI quail behave more as active copers. The corticosterone responses shown by LTI and STI quail under restraint stress suggest that adrenocortical correlates of coping behavior in these genotypes of quail may be different from the coping styles previously described in other species. Repeated restraint slightly decreased CORT responses to stress in all experimental groups, but more markedly in male STI quail, whereas adrenal sensitivity and maximum adrenal corticosterone response capacity did not change in any group. On the other hand, neither behavioral habituation nor sensitization processes occurred in the context of repeated restraint in female and male LTI quail and female STI quail, whereas the decreases observed in some behavioral responses were interpreted to be the result of a habituation process in male STI quail. (c) 2008 Published by Elsevier Inc.

International audience; Most tests used to study fear in birds involve transferring them to a novel environment, which constitutes a bias in studies aiming at identifying the neural correlates of a specific fear-inducing situation. In order to investigate fear in birds with minimum interference by humans, behavioural and endocrine responses to the presentation of a novel object in the home cage were investigated in two lines of Japanese quail divergently selected for long or short duration of tonic immobility, a behavioural index of fear. Presentation of the novel object induced typical fear responses (avoidance of the object, increased pacing and increased plasma corticosterone levels) that were similar in the two lines of quail. Presentation of a novel object in the home cage thus appears to be a suitable stimulus to induce fear reactions in quail, with minimum interference from other motivational systems. The fact that quail of both lines reacted similarly in this test, while they are known to differ greatly in their behavioural responses to other fear-inducing tests, illustrates the multidimensional nature of fear. (C) 2007 Elsevier B.V. All rights reserved.

Emotional reactivity modulates autonomic responses to an acoustic challenge in quail. Physio Behav 00(0) 000-000, 2006. This study investigated the relationship between emotional reactivity and behavioral and autonomic responses to an acoustic stimulus in quail. It was hypothesized that birds with high emotional reactivity would have higher motor inhibition combined with higher sympathetic activation than birds with low emotional reactivity. Two experiments were performed. The first looked for correlations between emotional reactivity, evaluated by a tonic immobility test, and motor and Heart Rate Variability in relation to an acoustic stimulus. The second experiment compared the motor and autonomic responses to the acoustic stimulus of quail selected on either long (LTI) or short (STI) duration of tonic immobility. The first experiment showed that the acoustic stimulation induced motor inhibition and cardiac activation. Correlations were found between tonic immobility duration and both autonomic activity before stimulation and sympathovagal balance after stimulation. In the second experiment, LTI quail showed strong sympathetic activation, whereas STI quail showed parasympathetic and sympathetic activation. The activation of the parasympathetic system induced by the noise in STI quail can be explained by the predominance of this system at rest in this line. In conclusion, both the basal autonomic activity and the autonomic responses differed according to the emotional reactivity, and changes in autonomic activity appear to be related to the genetic selection process.

CD26 exhibits a dipeptidylpeptidase-IV function (DPPIV) which regulates neuropeptide activity by N-terminal processing. Because abnormal plasma DPPIV was associated in mammals with behavioral changes, we examined the behavior of CD26-/- mice resulting from targeted inactivation of the gene. These animals had a decreased immobility in the forced swim and tail suspension tests, indicating a reduced depression-like behavior. We addressed some factors that could affect these results. No major differences between mutants and controls were observed in the black/white box test that investigates anxiety. In the hole-board apparatus that explores both curiosity and anxiety, CD26-/- mice of both genders made significantly more head dips than controls. In a motor activity test, mutants displayed higher horizontal and vertical activities i.e. increased novelty-induced behavioral activation. We conclude that DPPIV inactivation in mice broadly leads to an antidepressant-like and hyperactive phenotype.

The aims of this study were to investigate the existence of a circadian rhythm of basal corticosterone (B) plasma concentrations in male and female Japanese quail lines divergently selected for long (LTI) or short (STI) duration of tonic immobility (TI) and the possible effects of photoperiod length on corticotropic axis reactivity. Significant peaks in B levels were observed throughout the day in 3 out of the 4 groups used in our experiments. However, B levels remained very low for all groups (< 5.0 ng/mL) and there was no consensus between groups. We therefore have no evidence from our results that basal B levels follow a circadian rhythm in adult STI and LTI quail held under a long photoperiod (16L:8D). We also showed that rearing under a long photoperiod (16L:8D) was associated with higher basal B levels and higher B adrenal response capacity to 1-24 adrenocorticotropic hormone (ACTH) injection in the STI and LTI lines compared with a shorter period (8L:16D). Higher hypothalamic-pituitary-adrenal (HPA) axis responsiveness to restraint in a crush cage was also measured in female quail reared under the long photoperiod, and similar responses were measured under both photoperiods in males. This result suggests that the effects of photoperiod length involve both local and more central mechanisms in the control of HPA axis responsiveness according to sex. On the other hand, we showed that the genetic selection program for TI responses induced greater increases in the B level following restraint in STI quail than in LTI quail of both sexes under both photoperiods, but the B adrenal response capacity was similar for both lines and sexes. Although further investigations on both lines regarding adrenal sensitivity are necessary before being able to conclude definitively, our findings strongly suggest that the differences observed in HPA axis responsiveness to restraint between lines are probably not due to differences in adrenal function itself but may involve upstream structures of the HPA axis.

Neonatal handling affects the response to repeated stress in a sexually dimorphic manner. In order to elucidate the mechanisms underlying these gender-dependent effects, we investigated the consequences of neonatal androgenization and handling on adult stress reactivity by determining: (a) immobility time during repeated forced swimming, (b) plasma corticosterone levels, and (c) brain serotonin and dopamine levels and turnover after either repeated forced swimming, or repeated forced swimming followed by repeated restraint stress. In neonatally androgenized females, immobility time was lower in the handled than in the non-handled rats, a pattern resembling that of the males, suggesting that the sexually dimorphic effect of handling on immobility time can be attributed to the organizational effects of testosterone. No differences were found between androgenized females and females injected neonatally with vehicle, indicating that the gender differences in circulating corticosterone are not due to the organizational effects of testosterone. The stress of a neonatal injection interacted with neonatal handling resulting in lower plasma corticosterone and hypothalamic dopamine and serotonin levels in the neonatally injected handled animals following repeated forced swimming. The serotonergic system appears to be sensitive to both the organizational actions of testosterone and the effects of handling, since handled androgenized females had higher serotonin levels and decreased turnover following repeated forced swimming stress, compared to those injected neonatally with vehicle. Handling resulted in increased hypothalamic and striatal serotonin levels in both males and females following repeated forced swimming. Our results reveal that handling has gender-dependent effects on adult hypothalamic-pituitary-adrenal axis and brain monoaminergic system reactivity to stress and that these effects can be attributed to both the organizational and activational effects of gonadal hormones.