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Context Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. Aims The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. Methods The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). Key results The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. Conclusions These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. Implications These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

The Japanese quail is a powerful model to characterize behavioral, physiological, and neurobiological processes in Galliformes. Behavioral tests have already been adapted for quail to assess memory systems, but despite the pivotal role of the hippocampus in this cognitive process, its involvement in spatial memory has not been demonstrated in this species. In this study, lesions were created in the hippocampus of Japanese quail, and both lesioned and control quail were tested for spatial and cue-based learning performances. These hippocampal lesions specifically impacted spatial learning performance, but spared learning performance when birds could solve the task using their cue-based memory. These findings, thus, highlight that the hippocampus plays a crucial role and is essential for spatial declarative memory. Future studies could aim to elucidate the cellular or molecular mechanisms involved in this form of memory.

Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide first discovered in the quail brain that is involved in the control of reproductive physiology and behaviors, and stress response. GnIH gene encodes a second peptide, GnIH-related peptide-2 (RP2), the distribution and function of which remain unknown. We therefore studied GnIH-RP2 distribution by immunohistochemistry using a novel antibody capable of discriminating between GnIH and GnIH-RP2. The overall distribution of GnIH-RP2 is similar to that of GnIH. The vast majority of labeled neurons is located in the paraventricular nucleus (PVN) of the hypothalamus. Labeling of fibers is conspicuous in the diencephalon, but present also in the mesencephalon and telencephalon. Several regions involved in the control of reproduction and stress response (the PVN, septum, bed nucleus of the stria terminalis and nucleus commissura pallii) showed a dense network of immunolabeled fibers. To investigate the potential function of GnIH-RP2 we compared its expression in two quail lines genetically selected for divergence in their emotional reactivity. A quantitative analysis in the above-mentioned brain regions showed that the density of fibers was similar in the two lines. However, the number of GnIH-RP2 labeled neurons was higher in the median portion of the PVN in birds with higher emotional reactivity. These results point to a possible involvement of GnRH-RP2 in modulating stress response and/or emotional reactivity.

International audience; The common practice of artificially rearing lambs from prolific meat breeds of sheep constitutes a welfare issue due to increased mortality rates and negative health issues. In this multidisciplinary study, we investigated the possible short- and mid-term advantages of artificially feeding fresh ewe's milk instead of commercial milk replacer on lambs' growth, health and welfare. Romane lambs were either separated from their mothers on D3 and fed with Lacaune ewes' milk (LAC, n = 13) or milk replacer (REP, n = 15), or they were reared by their mothers (MOT, n = 15). On D45, they were weaned, gathered in single-sex groups until the end of the study on D150. Lamb performance and biomarkers of overall health were assessed by measuring: growth, dirtiness of the perianal area, enteric pathogens in the faeces, total antioxidant status and redox status assessed by plasma reduced glutathione/oxidised glutathione ratio, and immune response after vaccination against chlamydiosis. As an exploratory approach, blood cell transcriptomic profiles were also investigated. Last, qualitative behaviour assessment (QBA) was performed as an integrated welfare criterion. Lacaune ewes' milk and REP never differed in their average daily gain but grew less than MOT lambs in the early suckling period and just after weaning. No effect was detected afterwards. On D30, LAC and REP lambs had lower total antioxidant and higher redox status than MOT lambs but did not differ among themselves. Lacaune ewes' milk and MOT had a cleaner perianal area than REP lambs on D21, while faecal pathogen infection did not vary between the treatment groups. After vaccination, LAC also had a stronger immune response on D90 compared to REP lambs. Transcriptome analysis performed on D150 showed differential gene expression, mainly in relation to inflammatory, immune and cell cycle response, between male lambs of the LAC group and those of the MOT and REP groups. Based on QBA, LAC lambs never differed from MOT lambs in their general activity and varied from REP only on D21; REP lambs were always more agitated than MOT lambs. In conclusion, artificial milk feeding impaired early growth rate, health and emotional state mainly during the milk feeding period and at weaning. Feeding artificially reared lambs with fresh ewe's milk partly mitigated some of the negative effects induced by milk replacer but without achieving the full benefit of being reared by the mother. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of The Animal Consortium.

International audience; Chronic stress profoundly affects forms of declarative memory, such as spatial memory, while it may spare nondeclarative memory, such as cue-based memory. It is known, however, that the effects of chronic stress on memory systems may vary according to the level of training of an individual was submitted. Here, we investigated, in birds, how chronic stress impact spatial and cue-based memories according to training level. For that, control and chronically stressed Japanese quail were trained in a task that could be solved using spatial and cuebased memory and tested for their memory performance after 5 and 15 training days (initial training and overtraining, respectively) and following an emotional challenge (exposure to an open field). Our results showed that, compared to control quail, chronic stress impacted negatively spatial memory performances in stressed birds after initial training, but these differences were lowered after overtraining. Control birds seemed to shift from spatial to cue-based memory to solve the task across overtraining. However, an emotional challenge before testing reinstated the negative impact of chronic stress on spatial memory performances between the groups, revealing that chronic stress/overtraining did not eliminate the spatial memory and differences caused by stressors can reemerge depending on the individual?s immediate psychological state. Contrary to spatial memory, cue-based memory was not affected in chronically stressed birds compared to control birds in any test occasion, confirming its resistance against the negative effects of chronic stress. Altogether these findings reveal a dynamic dialogue between stress, training level, and memory systems in birds.

International audience; Prenatal maternal stress (PMS) influences many facets of offspring’s phenotype including morphology, behaviour and cognitive abilities. Recent research suggested that PMS also induced epigenetic modifications. In the present study, we analysed, in the Japanese quail, the effects of PMS on the emotional reactivity and cognitive abilities of the F1 offspring. We also investigated in the hippocampus, the paraventricular hypothalamic nucleus and subnuclei of the arcopallium/amygdala the level of two histone post-translational modifications, H3K4me2 and H3K27me3, known to be impacted by stress. We found that PMS does not affect F1 quail’s learning abilities but increases their emotional reactivity. Moreover, we demonstrated that PMS induced an increased density of H3K27me3 positive cells, in the hippocampus, paraventricular hypothalamic nucleus and dorsal nucleus of the amygdala, but not variations of H3K4me2. As these brain regions are involved in the control of vertebrates’ emotional responses, the effect of PMS on the epigenetic mark H3K27me3 could possibly be a mechanism involved in the behavioural effects we observed in F1 quail.

Avoidance of novelty, termed neophobia, protects animals from potential dangers but can also impair their adaptation to novel environments or food resources. This behaviour is particularly well described in birds but the neurobiological correlates remain unexplored. Here, we measured neuronal activity in the amygdala and the striatum, two brain regions believed to be involved in novelty detection, by labelling the early gene c-fos following chicks exposure to a novel food (NF), a novel object (NO) or a familiar food (FF). NF and NO chicks showed significantly longer latencies to touch the food, less time eating and emitted more fear-vocalizations than control chicks. Latency to touch the food was also longer for NO than for NF chicks. Significantly higher densities of c-fos positive cells were present in all the nuclei of the arcopallium/amygdala of NF and NO chicks compared to FF chicks. Also, NO chicks showed higher positive cell densities than NF chicks in the posterior amygdaloid, the intermediate and the medial arcopallium. Exposure to novel food or object induced a similar increase in c-fos expression in the nucleus accumbens and the medial striatum. Our data provide evidence activation of the arcopallium/amygdala is specific of the type of novelty. The activation of striatum may be more related to novelty seeking.

The effect of prolificacy on mother-young mutual recognition is still largely unknown in sheep. The aim of the present study was to investigate the ability of prolific ewes to develop an exclusive bond with their neonate and to recognize each other from alien subjects. Observations were performed on 11 D'man and 16 Romanov ewes with, respectively, 19 and 37 of their lambs. Maternal selectivity was tested at 24 h postpartum during two consecutive periods of 3 min. All mothers accepted their own lambs at suckling, while 21 out of 27 (78%) rejected the alien, thus displaying mostly selective nursing. To assess mother-young recognition, a two-choice test was performed at 36 h postpartum. Ewes clearly preferred their own lambs to an alien lamb and behavioral differences were not found between mothers of small (singletons and twins) and large litters (triplets and quadruplets). Romanov ewes reached their own lambsmore rapidly and spent more time near them than D'man ewes. Lambs from small litters, in particular light lambs, clearly preferred their mothers to an alien dam; however, both light and heavy lambs in large litters did not discriminate between the two stimulus ewes. D'man lambs clearly preferred their mothers to an alien dam; in contrast, such a preference was not as clearly demonstrated in Romanov lambs.

International audience; Recent studies provided evidence that a personality trait such as a trait for a high or a low emotionality can either promotes or impairs learning and memory performances. This variability can be partly explained because this trait may have opposite effect on memory performances depending on the memory system involved. The present study investigated in Japanese quail the relationships between emotionality and two forms of memory, spatial-memory and cue-based memory. We showed that birds with a high emotionality trait (E+), compared with birds with a low emotionality trait (E-), reached slowly but more accurately the spatial location of a rewarded cup in an arena that contains 8 identical cups. Then a second cohort of E + and E-quails was trained to solve a dual spatial/cued task in which they could use either their spatial or cue-based memory. Whereas E + birds predominantly solved the task using their spatial memory, E-birds preferentially used their cue-based memory. These findings demonstrate that a trait for a high emotionality, can influence spatial memory performances but also contributes to favor the selection of this form of memory.

International audience; The positive aspect of emotions, like pleasure, remains overlooked in birds. Our aim was to contribute to the exploration of facial indicators of positive emotions. To observe contrasting emotional expressions, we used two lines of Japanese quail divergently selected on their inherent fearfulness: a fearful line (long tonic immobility duration: LTI) and a less fearful line (short tonic immobility duration: STI). To induce positive emotions, we gave individual quail the opportunity to perform a rewarding behaviour, dustbathing, in an unfamiliar cage. More STI than LTI quail expressed dustbathing and latencies to dustbathe were significantly shorter in STI than LTI quail. This result indicated that the lines of quail differed in their fearfulness of the situation. We observed crown feather height, throat feather angle and pupil surface before (control) and during dustbathing. We found significant increases in crown feather height, pupil area and angle of throat feathers between the control and the dustbathing phases in STI quail, and pupil area correlated positively with crown feather height. In LTI quail, the angle of throat feathers increased during dustbathing, but the other parameters did not differ. We argue that variation in crown feather height and pupil area may provide indications of positive emotions in Japanese quail.

International audience; Profound behavioral changes occur in the mother at parturition, a time when the maternal brain undergoes extensive remodeling of neural circuits, especially in olfactory structures. Adult neurogenesis, a form of brain plasticity, could constitute an adaptive response to motherhood. The present study hypothesized that chemical disruption of olfactory neurogenesis would impair the establishment of maternal behavior in sheep. In addition, because ewes are able to learn the olfactory signature of their offspring, we also examined whether disruption of olfactory neurogenesis altered recognition of the familiar lamb. At one month of gestation, ewes received either infusion of the antimitotic drug Ara-C or saline into the lateral ventricles via one-month-long osmotic minipumps. Ara-C infusion dramatically decreased olfactory neurogenesis but spared hippocampal neurogenesis. Mothers exhibiting more than a 70% reduction in olfactory neurogenesis emitted fewer maternal bleats during the first hours after parturition. Reduction of olfactory neurogenesis also negatively affected discrimination of the familiar lamb. Differences in ewes’ aggressive behavior toward familiar and alien lambs were observed in sham mothers, but not in mothers with reduced olfactory neurogenesis. In addition, when ewes were given the choice between familiar and unfamiliar anesthetized lambs, so that only olfactory cues were available, mothers with a reduction in neurogenesis greater than 70% were not able to discriminate their own lamb from an alien lamb. These results indicate that adult-born olfactory neurons are to some extent involved in the establishment of maternal behavior in sheep by contributing to the processing of offspring odors.

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International audience; The periaqueductal gray (PAG) is a mesencephalic brain structure organised in subdivisions with specific anatomical connections with the rest of the brain. These connections support the different PAG functions and especially its role in emotion. Mainly described in territorial and predatory mammals, examination of the PAG connections suggests an opposite role of the ventral and the dorsal/lateral PAG in passive and active coping style, respectively. In mammals, the organisation of PAG connections may reflect the coping style of each species. Based on this hypothesis, we investigated the anatomical connections of the PAG in sheep, a gregarious and prey species. Since emotional responses expressed by sheep are typical of active coping style, we focused our interest on the dorsal and lateral parts of the PAG. After injection of fluorogold and fluororuby, the most numerous connections occurred with the anterior cingulate gyrus, the anterior hypothalamic region, the ventromedial hypothalamic nucleus and the PAG itself. Our observations show that the sheep PAG belongs to the neuronal circuit of emotion and has specific parts as in other mammals. However, unlike other mammals, we observed very few connections between PAG and either the thalamic or the amygdalar nuclei. Interestingly, when comparing across species, the PAG connections of sheep were noticeably more like those previously described in other social species, rabbits and squirrel monkeys, than those in territorial species, rats or cats.

Remerciements : Plateforme Phénotypage-Endocrinologie, INRA, UMR PRC 0085, Centre Tours Val de Loire; International audience; Characteristics of attachment were assessed in peer- and object-reared lambs, and compared to mothered subjects by taking into consideration distress, proximity seeking, and exploration during two separation-reunion tests in both the familiar and a novel environment. Plasma cortisol and oxytocin were assayed as physiological indicators of stress and being comforted during the separation-reunion test. Rewarding properties of the familiar figures were also determined in a conditioned place preference-like paradigm. Between-group analysis revealed the existence of secure attachment with the mother, alteration of secure attachment with the peer and weaker attachment with the object. Weaker attachment was expressed by a lack of distress during separation in the home pen and no preference for the place conditioned with the familiar object. Elevated basal plasma oxytocin levels, but not cortisol, observed in maternally deprived lambs were more likely linked to the absence of a maternal figure rather than social comfort during reunion.

In this study, we assessed whether prenatal exposure to elevated yolk steroid hormones can influence in ovo chemosensory learning and the behavior of domestic chicks. We simulated a maternal environmental challenge by experimentally enhancing yolk progesterone, testosterone, and estradiol concentrations in hen eggs prior to incubation. The embryos from these hormones-treated eggs (HO) as well as sham embryos (O) that had received the vehicle-only were exposed to the odor of fish oil (menhaden) between embryonic Days 11 and 20. An additional group of control embryos (C) was not exposed to the odor. All chicks were tested following hatching for their feeding preferences between foods that were or were not odorized with the menhaden odor. In the 3-min choice tests, the behavior of O chicks differed significantly according to the type of food whereas C and HO chicks showed no preference between odorized and non-odorized food. Our result suggests weaker response in HO chicks. In addition, HO chicks showed impaired growth and reduced intake of an unfamiliar food on the 24-h time scale compared to controls. Our data suggest that embryonic exposure to increased yolk hormone levels can alter growth, chemosensory learning, and the development of feeding behaviors.

While behavioral mechanisms of bonding between young mammals and humans have been explored, brain structures involved in the establishment of such processes are still unknown. The aim of the study was to identify brain regions activated by the presence of the caregiver. Since human positive interaction plays an important role in the bonding process, activation of specific brain structures by stroking was also examined. Twenty-four female lambs reared in groups of three were fed and stroked daily by a female caregiver between birth and 5–7 weeks of age. At 4 weeks, an isolation-reunion-separation test and a choice test revealed that lambs developed a strong bond with their caregiver. At 5–7 weeks of age, lambs were socially isolated for 90 min. They either remained isolated or met their caregiver who stroked them, or not, at regular intervals over a 90-min period. Neuronal activation was investigated at the end of the period for maximum c-Fos expression. Reunion with the caregiver appeased similarly the lambs whether stroking was provided or not. Stroking did not activate a specific brain network compared to no stroking. In both cases, brain regions associated with olfactory, visual and tactile cue processing were activated in the presence of the caregiver, suggesting a multisensory process involved. In addition, activation of the oxytocinergic system in the hypothalamic paraventricular nucleus induced by the presence of the caregiver suggests similar neuroendocrine mechanisms involved in inter-conspecific and animal-human bonding.

In this study, we assessed whether prenatal exposure to elevated yolk steroid hormones can influence in ovo chemosensory learning and the behavior of domestic chicks. We simulated a maternal environmental challenge by experimentally enhancing yolk progesterone, testosterone, and estradiol concentrations in hen eggs prior to incubation. The embryos from these hormones-treated eggs (HO) as well as sham embryos (O) that had received the vehicle-only were exposed to the odor of fish oil (menhaden) between embryonic Days 11 and 20. An additional group of control embryos (C) was not exposed to the odor. All chicks were tested following hatching for their feeding preferences between foods that were or were not odorized with the menhaden odor. In the 3-min choice tests, the behavior of O chicks differed significantly according to the type of food whereas C and HO chicks showed no preference between odorized and non-odorized food. Our result suggests weaker response in HO chicks. In addition, HO chicks showed impaired growth and reduced intake of an unfamiliar food on the 24-h time scale compared to controls. Our data suggest that embryonic exposure to increased yolk hormone levels can alter growth, chemosensory learning, and the development of feeding behaviors.

Ewes form a selective olfactory memory for their lambs offer 2 hr of mother young interaction following parturition Mothers will subsequently reject any strange lamb at suckling The present study investigated whether artificial vaginocervical stimulation (VCS) allows the formation of a selective bond with an unfamiliar Iamb and whether it interferes with the maintenance of the bond formed with the familiar lamb At 2 hr postpartum, mothers were separated from then familial lamb after having formed a selective bond with it and were given 10 nun of mechanical VCS. In the "VCS + lamb" group (n = 24) an unfamiliar lamb was left with the ewe for 2 hr whereas in the "VCS no lamb" group (n = 26) the mother was left alone for the same period of tune Ewes of the "no VCS" group (n = 14) did not receive any VCS In the majority of animals of the "VCS + lamb" group (23/24) VCS induced a complete acceptance of the unfamiliar lamb without any disruption of the bond previously formed with the familiar lamb VCS or 2 hr of reparation did not disrupt the maintenance of the selective bond initially formed with the familiar Iamb since all the ewes of the "VCS no lamb" and "no VCS'' groups accepted it at suckling (C) 2010 Wiley Periodicals, Inc Dev Psychobiol 52 537-544, 2010

This study used animal models to examine potential similarities between dependence on physical activity (i.e., exercise) and dependence on morphine. Using C57BL/6 mice, the study also tested the hypothesis that physical exercise (e.g., long-term wheel running) may enhance vulnerability to the development of morphine dependence. The existence of an endorphin-related dependence induced by physical activity was also assessed. Naloxone was used to precipitate morphine withdrawal in mice accustomed to morphine. Specifically, the study sought to assess the intensity of addiction provoked by injection of morphine in mice that engaged in wheel-running activity as opposed to inactive mice. After 25 days of free access to activity wheel, mice that engaged in wheel-running demonstrated increased vulnerability to naloxone-induced withdrawal symptoms, which may be linked to activation of peripheral, as opposed to central, opioid receptors. These results indicate a behavioral interaction in which engaging in wheel running appears to potentiate the effects of morphine addiction. Implications of these findings for understanding human behavior and exercise addiction are also discussed.

Social factors hypotheses predict that social segregation between male and female adult ungulates is due to social preferences among same-sex peers and avoidance of the opposite sex, rather than aggregation due to body size dimorphism and differential needs of the sexes. It is suggested that if such social preference/avoidance exists its roots should be early in life. While juvenile ungulate males show social preference for same-sex and same-age peers a few weeks after birth, no studies have confirmed such a phenomenon in juvenile females. In this study we investigated another possible mechanism that would result in an early social preference for same-sex conspecifics among juvenile females: we hypothesized that offspring–mother attachment is stronger for daughters than for sons. Attachment was measured in lambs, Ovis aries, using three characteristics defined initially in children: proximity seeking, distress following separation and exploration in the mother's presence. Lambs were tested at 3 weeks of age in two experimental situations in which they could interact with the mother, a familiar ewe or an unfamiliar ewe. (1) During a choice test between the mother and the familiar ewe, daughters maintained closer proximity with the mother than sons did. During the test without the mother (a familiar versus an unfamiliar ewe) daughters were more distressed than sons were. (2) In an isolation–reunion–separation test, reunion with the mother increased exploratory behaviour more in daughters than in sons. Overall, our results reveal that daughters displayed stronger attachment behaviours and could be more strongly attached to their mother than sons are. Such early preference may be a key factor leading to social preference among females and social segregation between the sexes.

Testosterone-dependent olfactory signals emitted by male are well known to accelerate female puberty in mice (Vandenbergh effect). However, it remains unclear whether these chemosignals also influence adult expression of male-directed odor preference. Therefore, we exposed female mice to intact or castrated male bedding (vs clean bedding as control) during the peripubertal period (postnatal day (PD) 21–38) and measured male-directed odor preference in adulthood. At PD45 or PD60, females exposed to intact male odors, and thus showing puberty acceleration, preferred to investigate odors from intact males over females or castrated males. Females exposed to castrated male odors did not show puberty acceleration but preferred male (intact or castrated) over female odors. Finally, control females did not show any odor preference when tested at PD45, although a preference for male odors emerged later (PD60). In a second experiment, females that were exposed to intact male odors after pubertal transition (PD36–53) also preferred intact male over castrated male odors. In conclusion, our results indicate that peripubertal exposure to male odors induced early expression of male-directed odor preference regardless of puberty-accelerating effect and that induction of male-directed odor preference is not specific to the peripubertal period.

Remerciements : INRA, UMR PRC Plate-forme CIRE 37380 Nouzilly; Sheep are gregarious mammals with complex social interactions. As such, they are very sensitive to social isolation and constitute a relevant animal model to study specifically the biological consequences of social stress. We examined previously the behavioral and endocrine responses in ewes isolated socially in the familiar conspecific withdrawal model (FCW) and showed that stressful responses increased and maintenance behaviors decreased, confirming that social isolation is a strong stressor in sheep. Melatonin synchronizes seasonal and circadian rhythms; and several studies reported its implication in cognitive processes as emotion. Here we investigated its role in the modulation of social stressful responses. Firstly, we studied ewes in the FCW model during the day (characterized by low melatonin levels) and the night (characterized by high melatonin levels). We found lower stressful responses (significant lower levels of cortisol plasma, number of foot pawings, of circling attempts) during the night as compared to the day. To investigate whether these effects were due to melatonin or to darkness, we submitted ewes to FCW during the night with lights on, a condition that suppresses melatonin secretion. Ewes infused with melatonin under these conditions showed decreased stressful responses (significant lower levels cortisol plasma, number of vocalizations, time spent with the head out of the cage) as compared to ewes infused with saline. These findings demonstrate that melatonin diminishes the endocrine and behavioral impact of social isolation in ewes and support the idea that melatonin has a calming effect in socially stressful situations.

International audience

We assessed the development of individual discrimination resulting from direct contact/familiarization in ewes. Unfamiliar ewes were introduced during 6, 24 or 72 h in groups of already familiarized ewes. At the end of this contact period, the development of social recognition with the animal that has been introduced was assessed using two different types of tests: a Y-maze preference test and a delayed paired close encounters test where tested ewes are successively and randomly interacting with the familiar animal and an unfamiliar conspecific. The results of both tests showed that ewes developed a recognition of the familiar animal in comparison to a completely unfamiliar female. However, this preference was evidenced after 24 h of contact when using the paired close encounters test whereas it appears only after 72 h when using the Y-maze test, suggesting that the paired close encounters test is a more sensitive methodology to assess the development of social familiarization. The importance of estrogens, in the formation of social familiarization was also evaluated. To this end, social recognition in the paired close encounters test was compared between ovariectomized animals receiving estrogen implants or not. Despite significant high levels of estradiol in estrogen implanted females, no major differences in recognition appeared between groups, suggesting that in our conditions estrogens do not have major influence on social familiarization.

International audience; In synucleinopathies, including Parkinson's disease, partially ubiquitylated alpha-synuclein species phosphorylated on serine 129 (P(S129)-alpha-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against alpha-synuclein-mediated toxicity in various models.We analyzed the effects of Parkin deficiency in a mouse model of synucleinopathy to explore the possibility that Parkin and alpha-synuclein act in the same biochemical pathway. Whether or not Parkin was present, these mice developed an age-dependent neurodegenerative disorder preceded by a progressive decline in performance in tasks predictive of sensorimotor dysfunction. The symptoms were accompanied by the deposition of P(S129)-alpha-synuclein but not P(S87)-alpha-synuclein in neuronal cell bodies and neuritic processes throughout the brainstem and the spinal cord; activation of caspase 9 was observed in 5% of the P(S129)-alpha-synuclein-positive neurons. As in Lewy bodies, ubiquitin-immunoreactivity, albeit less abundant, was invariably co-localized with P(S129)-alpha-synuclein. During late disease stages, the disease-specific neuropathological features revealed by ubiquitin- and P(S129)-alpha-synuclein-specific antibodies were similar in mice with or without Parkin. However, the proportion of P(S129)-alpha-synuclein-immunoreactive neuronal cell bodies and neurites co-stained for ubiquitin was lower in the absence than in the presence of Parkin, suggesting less advanced synucleinopathy. Moreover, sensorimotor impairment and manifestation of the neurodegenerative phenotype due to overproduction of human alpha-synuclein were significantly delayed in Parkin-deficient mice.These findings raise the possibility that effective compensatory mechanisms modulate the phenotypic expression of disease in parkin-related parkinsonism.

International audience; The present study investigated whether deprivation of nursing or of any physical interaction with the lamb impairs the onset of maternal responsiveness and the establishment of selectivity in primparous and multiparous ewes. just after parturition, ewes could interact freely with their lamb, or could only lick their lamb but not nurse them, or could neither lick nor nurse them for the first 4h. At 4h, mothers were successively observed for 3 min with an alien lamb and then with their own lamb. Only 5/14 primiparous mothers accepted their own lamb following deprivation of all physical contact whereas all multiparous mothers did so (19/19). Also, deprivation of all physical contact resulted in a significantly higher proportion of multiparous mothers accepting an alien lamb (6/18) than following deprivation of nursing only (0/19) indicating an impairment in selectivity. Finally, there was no indication that preventing only nursing led to a deficit either in maternal responsiveness or selectivity, neither in primiparous nor in multiparous ewes. These findings underline the importance of perception of olfactory cues from amniotic fluids through licking and/or physical contact and interacting with the lamb for the development of maternal responsiveness and selectivity. (C) 2009 Elsevier B.V. All rights reserved.