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Background Enacted or anticipated stigma among people living with HIV (PLHIV) can negatively impact healthcare engagement. We identified factors associated with having avoided HIV health services for fear of stigma among PLHIV in Morocco. Methods The Stigma Index survey was conducted in Morocco in March-June 2016. Factors associated with avoiding HIV testing and treatment services for fear of stigma by (A) health personnel or family/neighbours and (B) health personnel and family/neighbours compared to people who did not avoid health services for fear of stigma from either of the two sources were assessed using multinomial logistic regression models. Results Among 583 respondents, 280 (48.0%) were women and median number of years living with HIV was 5[IQR:2–7]. Half of the respondents reported avoiding health services for fear of stigma by health personnel and/or family/neighbours: (A) n = 228, 39.1% and (B) n = 68, 11.7%. After adjustment on perceived health status, not having had easy access to antiretroviral treatment ((A) aRR [95% CI] = 1.76[1.16; 2.68]; (B) 2.18[1.11; 4.27]), discrimination by PLHIV ((A) 1.87[1.12; 3.13]; (B) 3.35[1.63; 6.88]) and exclusion from social activities ((A) 1.70[1.10; 2.61]; (B) 2.63[1.39; 5.00]) were associated with having avoided health services for fear of stigma by health personnel or/and family/neighbours. Being female (2.85[1.48; 5.47]), not having been referred for an HIV test for suspected symptoms 3.47[1.67; 7.22], having discussed sexual/reproductive health with a health professional (4.56[2.38; 8.71]), and not having the feeling to influence decisions on local projects for PLHIV (3.47[1.37; 7.83], were associated with having avoided health services for fear of stigma by both sources. Conclusion Results suggest a cumulative effect of fear of stigma and discrimination among PLHIV in Morocco. PLHIV who have experienced discrimination may seek to avoid similar situations at the expense of their health. These results should inform multi-level interventions and broader advocacy efforts to reduce stigma and discrimination.

Background Whiplash-associated disorders have been the subject of much attention in the scientific literature and remain a major public health problem. Objective Measure the impact of a validated information booklet on the fear-avoidance beliefs of emergency physicians and their approach to management regarding the treatment of whiplash-associated disorders. Methods A prospective cluster randomized controlled study conducted with a sample of emergency medicine physicians. Fear-avoidance beliefs were measured using The Whiplash Belief Questionnaire (WBQ) and Fear-Avoidance Beliefs Questionnaire (FABQ). We assessed the approach to management based on the prescription of pharmacological and non-pharmacological treatments based on the advice given to patients. The validated information booklet was the French version of The Whiplash Book. A set of questionnaires was sent to participants pre- and post-intervention. The experimental intervention was the provision of The Whiplash Book. The control arm did not receive any training or information. Results Mean fears and beliefs scores on inclusion were high: WBQ = 19.09 (± 4.06); physical activity FABQ = 11.45 (± 4.73); work FABQ = 13.85 (± 6.70). Improvement in fear-avoidance beliefs scores being greater in the intervention group was further confirmed by the variation in WBQ (-20 [-32; -6] vs. -6 [-16; 9]; p = 0.06), physical activity FABQ (-70 [-86; -50] vs. -15 [-40; 11]; p < 0.001), and work FABQ (-40 [-71; 0] vs. 0 [-31; 50]; p = 0.02). The emergency physicians' initial approach to management was not consistent with current guidelines. Reading the French version of The Whiplash Book could contribute to changing their approach to management in several areas on intra-group analysis. Conclusion The French version of The Whiplash Book positively influenced fear-avoidance beliefs among emergency physicians.

International audience; A falls prevention programme has been initiated in balneotherapy at Balaruc-les-Bains.Aims: To determine the health profiles of subjects who are at risk of falls, over 65 years of age and attending balneotherapy.Methods: Questionnaires were used to evaluate people on their fear of falling. Fatigue was assessed by visual analog scale as well as by functional status over the past 12 months. EQ-5D-3L, the IPAQ questionnaire and Fried's frailty scale were all used. Patients' functional capabilities were tested using the Unipedal stance test, the TUG test, the SPPB, the Tandem walking test and the isometric manual grip strength test.Results: Out of the 1471 patients (72.45 years ± 5.10), the women (67%) were tested. In the last 12 months, 485 of these 1471 patients fell (33%) and 37% of them suffered a severe injury. 45-50% of these subjects are now in good health. Women had a significantly higher impaired perception of their health than men (0.02 < p < 0.0001). According to Fried's criteria, 10.2% of the population is considered frail, with a significantly greater number of women (p < 0.0001). Static equilibrium was subnormal (less than 12 s during the TUG). The number of steps in tandem position discriminates individuals and gender as does the speed of moving from A to B and muscular strength.Conclusions: More than one-third of the subjects (more women than men) aged 65 or older visiting the Balaruc-les-Bains health resort are pre-frail or frail. They all have a recent history of falls, suffer from impaired muscle strength, and have balance and gait disorders.

International audience; Pavlovian conditioning is the reference paradigm for the study of associative learning based on the programmed relation of two stimuli, the conditioned stimulus (CS) and the unconditioned stimulus (US). Some authors believe that learning the CS-US interval is a co-requisite of or a pre-requisite to learning the CS-US association. There is a substantial literature showing that the amygdala is a critical player in Pavlovian conditioning, with both aversive and appetitive USs. We review a sparse but growing body of literature suggesting that the amygdala may also participate in processing the timing of the CS-US interval. We discuss whether the amygdala, in particular its central, basal and lateral nuclei, in concert with the network it belongs to, may play a role in learning the CS-US interval. We also suggest new and dedicated strategies that would result in better knowledge of the neural mechanisms underlying the learning of the CS-US time interval in isolation from the CS-US association.

International audience; PURPOSE: We conducted a population-based study of epilepsy in Prey Veng (Cambodia) to explore self-esteem, fear, discrimination, knowledge-attitude-practice (KAP), social-support, stigma, coping strategies, seizure-provoking factors, and patient-derived factors associated with quality of life (QOL). METHODS: The results are based on a cohort of 96 cases and matched controls (n = 192), randomly selected from the same source population. Various questionnaires were developed and validated for internal consistency (by split-half, Spearman-Brown prophecy, Kuder-Richardson 20), content clarity and soundness. Summary, descriptive statistics, classical tests of hypothesis were conducted. Uncorrected chi-square was used. Group comparison was done to determine statistically significant factors, for each domain, by conducting logistic regression; 95% confidence interval (CI) with 5% (two-sided) statistical significance was used. KEY FINDINGS: All questionnaires had high internal consistency. Stress was relevant in 14.0% cases, concealment in 6.2%, denial in 8.3%, negative feelings in public in 3.0%. Mean self-esteem was 7.5, range 0-8, related to seizure frequency. Mean discrimination was least during social interactions. Coping strategies were positive (e.g. look for treatment). Postictal headache, anger, no nearby health facility, etc. were associated with QOL. SIGNIFICANCE: The reliability of our questionnaires was high. A positive social environment was noted with many infrequent social and personal prejudices. Not all populations should (by default) be considered as stigmatized or equipped with poor KAP. We addressed themes that have been incompletely evaluated, and our approach could therefore become a model for other projects.

International audience; We studied 7,897 women with postmenopausal osteoporosis to assess factors that influence health-related quality of life (HRQoL). An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL. Understanding the factors that affect HRQoL may improve management of these patients.INTRODUCTION:HRQoL is impaired in women treated for postmenopausal osteoporosis (PMO). The objective of this study was to examine the relationship between clinical characteristics, comorbidities, medical history, patient demographics, and HRQoL in women with PMO.METHODS:Baseline data were obtained and combined from two large and similar multinational observational studies: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) and in the US (POSSIBLE US™) including postmenopausal women in primary care settings initiating or switching bone loss treatment, or who had been on bone loss treatment for some time. HRQoL measured by health utility scores (EQ-5D™) were available for 7,897 women (94 % of study participants). The relationship between HRQoL and baseline clinical characteristics, medical history and patient demographics was assessed using parsimonious, multivariable, mixed-model analyses.RESULTS:Median health utility score was 0.80 (interquartile range 0.69-1.00). In multivariable analyses, young age, low body mass index, previous vertebral fracture, increased number of comorbidities, high fear of falling, and depression were associated with reduced HRQoL. Regression-based model estimates showed that previous vertebral fracture was associated with lower health utility scores by 0.08 (10.3 %) and demonstrated the impact of multiple comorbidities and of fear of falling on HRQoL.CONCLUSIONS:In this large observational study of women with PMO, there was substantial interindividual variability in HRQoL. An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL.

Adult learning and memory functions are strongly dependent on neonatal experiences. We recently showed that neonatal odor-shock learning attenuates later life odor fear conditioning and amygdala activity. In the present work we investigated whether changes observed in adults can also be observed in other structures normally involved, namely olfactory cortical areas. For this, pups were trained daily from postnatal (PN) 8 to 12 in an odor-shock paradigm, and retrained at adulthood in the same task. 14C 2-DG autoradiographic brain mapping was used to measure training-related activation in amygdala cortical nucleus (CoA), anterior (aPCx), and posterior (pPCx) piriform cortex. In addition, field potentials induced in the three sites in response to paired-pulse stimulation of the olfactory bulb were recorded in order to assess short-term inhibition and facilitation in these structures. Attenuated adult fear learning was accompanied by a deficit in 2-DG activation in CoA and pPCx. Moreover, electrophysiological recordings revealed that, in these sites, the level of inhibition was lower than in control animals. These data indicate that early life odor-shock learning produces changes throughout structures of the adult learning circuit that are independent, at least in part, from those involved in infant learning. Moreover, these enduring effects were influenced by the contingency of the infant experience since paired odor-shock produced greater disruption of adult learning and its supporting neural pathway than unpaired presentations. These results suggest that some enduring effects of early life experience are potentiated by contingency and extend beyond brain areas involved in infant learning.

International audience; BackgroundHIV-related stigma diminishes the quality of life of affected patients. Little is known about perceived and enacted stigma of HIV-infected children in resources-limited settings. We documented the prevalence of perceived stigma and associated factors associated among children on antiretroviral therapy (ART) at a referral hospital in Cambodia.MethodsAfter informed consent, a standardized pre-tested 47-item questionnaire was confidentially administered to consecutive children (7 to 15 years) or their guardians if the child was 18 months to 6 years, during their routine ART visits. The questionnaire explored the sociodemographics of the child and the parents, HIV history, adherence to ART, tolerance of ART and perceived stigma. Associations between perceived stigma and the children¿s characteristics were measured by bivariate and multivariate analyses.ResultsOf 183 children, 101 (55.2%) had lost at least one and 45 (24.6%) both parents; 166 (90.7%) went to school. Of 183 children (female:84, 45.9%, median age 7.0 years, interquartile range: 2.0-9.6), 79 (43.2%) experienced perceived stigma, including rejection by others (26.8%), no invitations to social activities (18.6%) and exclusion from games (14.2%). A total of 43 (23.5 %) children were fearful of their disease and 61 (53.9%) of 113 older than 6 years reported knowledge of their HIV status. Of 136 children over five years and eligible for education, 7 (3.8%) could not go to school due to perceived stigma. Incomplete adherence to ART was reported for 17 (9.2%) children. In multivariate analysis, school attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.0-7.9) and income of less than one dollar per person per day (OR: 2.2, 95%CI: 1.1-4.5) were associated with perceived stigma. Conversely, receipt of social support (OR: 0.4, 95% CI 0.2-0.9) was associated with lower risk of perceived stigma.ConclusionPerceived stigma in pediatric ART patients remains a significant issue in Cambodia. Psychological support and interventions should be developed in hospitals, schools, and underprivileged communities to prevent HIV-related stigma for affected children.

International audience; Although it is believed that different types of memories are localized in discreet regions of the brain, concrete experimental evidence of the existence of such engrams is often elusive. Despite being one of the best characterized memory systems of the brain, the question of where fear memories are localized in the brain remains a hotly debated issue. Here, we combine site-specific behavioral pharmacology with multisite electrophysiological recording techniques to show that the lateral nucleus of the amygdala, long thought to be critical for the acquisition of fear memories, is also an essential locus of fear memory storage.

International audience; Many of the behavioral consequences of stress are mediated by the activation of the glucocorticoid receptor by stress-induced high levels of glucocorticoid hormones. To explore the molecular mechanisms of these effects, we combined in vivo and in vitro approaches. We analyzed mice carrying a brain-specific mutation (GR(NesCre)) in the glucocorticoid receptor gene (GR, also called Nr3c1) and cell lines that either express endogenous glucocorticoid receptor or carry a constitutively active form of the receptor (DeltaGR) that can be transiently induced. In the hippocampus of the wild-type [corrected] mice after stress, as well as in the cell lines, activation of glucocorticoid receptors greatly increased the expression and enzymatic activity of proteins in the MAPK signaling pathway and led to an increase in the levels of both Egr-1 mRNA and protein. In parallel, inhibition of the MAPK pathway within the hippocampus abolished the increase in contextual fear conditioning induced by glucocorticoids. The present results provide a molecular mechanism for the stress-related effects of glucocorticoids on fear memories.

International audience; Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.

International audience; When reactivated, memories enter a labile, protein synthesis-dependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is selective to the reactivated memory, and that disruption of reconsolidation is correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter memories via synaptic plasticity at selectively targeted synapses.

International audience; Olfactory neurons in the nasal mucosa have the capacity to regenerate continuously along the lifespan by neurogenesis processes starting with progenitor cells close to the basal lamina. The cellular turnover into olfactory neuroepithelium may be modified by environmental stimuli insofar as nasal mucosa is directly in contact with airborne chemicals. However, few studies have been focused on selective changes, especially those concerning mature olfactory neurons and basal cells during specific inhalation exposure. Among chemicals, solvents are known to induce changes in smell abilities and concomitant histological and cellular modifications related to the type of molecule, concentration and time of exposure. This study was designed to characterize smell sensitivity (using behavioral tests) and immunohistochemical effects on olfactory neuroepithelium induced by pyridine exposure in mice. Olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) were used to characterize respectively mature olfactory neurons and basal cells. Results showed that inhalation exposure to pyridine had no impact on smell sensitivity whatever the concentration used and the time of exposure. These findings were in agreement with immunohistochemical measurements showing the same cellular kinetic whatever the condition of exposition to pyridine. Indeed, OMP-positive cells increased and PCNA-positive cells decreased as early as the beginning of exposure and cell amounts remained stable at this level until the end of exposure. These findings suggest that pyridine could have the property to rapidly activate a cellular turnover from basal cell progenitors. Rather than toxic effects, the present findings suggest that the metabolites of pyridine might have cell cycle activation properties.

Background: The aim of the present study was to assess the possibility of compensating early facial expression recognition impairments in amnestic Mild Cognitive Impairment (a-MCI) patients. Methods: Twelve patients with a-MCI and 17 healthy participants matched according to age and education participated in the study. The originality of the present study was to cue the recognition of facial expressions (happiness, anger, fear, and neutral) by comparing eye region expressions and entire facial expressions. Results: A deficit in the recognition of fearful expressions was observed in a-MCI patients relative to the control group, whereas recognition of all the other emotional expressions was spared. Nevertheless, when eye expressions cued the recognition of fearful facial expressions, the performance of normal controls and a-MCI patients was comparable. Conclusion: The present paper indicates a selective impairment in fear recognition in the prodromal state of Alzheimer’s disease, and the possibility of compensating this deficit by orienting selective attention on specific facial features.

International audience; Adult behavioral and physiological responses are partly dependent on neonatal experiences. In several animal species, enriched/aprovished environments and stressful/appeasing events are crucial in the setting of adaptative behaviors. However, little is known about the effects of postnatal exposure to predator odor (as unconditioned fear-related stimulus) on spatial learning at adulthood. Thus, the aim of the present study was to investigate the effects of a postnatal exposure to 2,4,5-trimethylthiazoline (TMT, as a predator odor) on radial arm maze (RAM), Tolman maze (TM) and Morris water maze (MWM) in mice at adulthood. The results showed that a TMT group constituted by mice exposed postnatally during 3 weeks to TMT presented significantly better spatial learning achievements in adulthood compared to a water group, postnatally exposed to water only, as well as compared to a butanol group (butanol used as an odor without ecological significance) exposed postnatally to butanol during 3 weeks.

International audience; Environmental stimuli and adverse experiences in early life may result in behavioral and physiological changes in adulthood. In several animal species, the odors cues are crucial in the setting of adaptive behaviors, especially towards predators. However, little is known about the effects of postnatal exposure to predator odor on the later physiological and behavioral responses to this natural stressor. Thus, the aim of this study was to investigate the effects of a postnatal exposure to synthetic predator odor (TMT) in mice pups on later adult fear-related behaviors and corticosterone levels in response to this specific stimulus. Pups postnatally exposed to only water showed later in adult life behavioral responses when exposed to TMT that were statistically different from mice that were exposed as neonates to TMT. In addition, mice exposed as neonates to TMT showed a decrease of fear-related behaviors while no differences occurred in the corticosterone levels between both groups.

International audience; Two experiments were conducted to investigate the effect of a threatening stimulus in human adults in a temporal bisection task. In Experiment 1, for two anchor duration conditions (400/800 vs. 800/1600 ms), the participants completed trials in which the probe duration was followed by an aversive stimulus or a nonaversive stimulus. The results showed that the duration was judged longer when the participants expected an aversive rather than a nonaversive stimulus. In Experiment 2, the effect of the temporal localization of the aversive stimulus was also tested, with the aversive stimulus being presented at the beginning or at the end of the probe duration. The results revealed a temporal overestimation in each condition compared to the trials in which no aversive stimulus was presented. Furthermore, the temporal overestimation was greater when the expectation for the forthcoming threatening stimulus was longer. This temporal overestimation is explained in terms of a speeding-up of the neural timing system in response to the increase in the arousal level produced by the expectation of a threatening stimulus.

BackgroundTo investigate hedonic reactivity and the influence of unconscious emotional processes on the low sensitivity to positive reinforcement of food in anorexia nervosa (AN).MethodAN and healthy women were exposed to palatable food pictures just after a subliminal exposure to facial expressions (happy, disgust, fear and neutral faces), either while fasting or after a standardized meal (hungerversussatiety). Both implicit [facial electromyographic (EMG) activity from zygomatic and corrugator muscles, skin conductance, heart rate, and videotaped facial behavior] and explicit (self-reported pleasure and desire) measures of affective processes were recorded.ResultsIn contrast to healthy women, the AN patients did not display objective and subjective indices of pleasure to food pictures when they were in the hunger states. Pleasure to food cues (liking) was more affected than the desire to eat (wanting) in AN patients. Subliminal ‘fear faces’ increased corrugator muscle reactivity to food stimuli in fasting AN patients, as compared to controls.ConclusionsThe results suggest that unconscious fear cues increase the negative appraisal of alimentary stimuli in AN patients and thus contribute to decreased energy intake.

International audience; The B-raf proto-oncogene exerts essential functions during development and adulthood. It is required for various processes, such as placental development, postnatal nervous system myelination and adult learning and memory. The mouse B-raf gene encodes several isoforms resulting from alternative splicing of exons 8b and 9b located in the hinge region upstream of the kinase domain. These alternative sequences modulate the biochemical and biological properties of B-Raf proteins. To gain insight into the physiological importance of B-raf alternative splicing, we generated two conditional knockout mice of exons 8b and 9b. Homozygous animals with a constitutive deletion of either exon are healthy and fertile, and survive up to 18 months without any visible abnormalities, demonstrating that alternative splicing is not essential for embryonic development and brain myelination. However, behavioural analyses revealed that expression of exon 9b-containing isoforms is required for B-Raf function in hippocampal-dependent learning and memory. In contrast, mice mutated on exon 8b are not impaired in this function. Interestingly, our results suggest that exon 8b is present only in eutherians and its splicing is differentially regulated among species.

International audience; OBJECTIVE: We aimed to assess fear-avoidance beliefs in patients with acute low back pain (LBP) and to identify features of patients and general practitioners (GPs) associated with patients' fear-avoidance beliefs. METHODS: A cross-sectional study conducted in primary care practice in France. A total of 709 GPs completed a self-administered questionnaire assessing fear-avoidance beliefs [the Fear-Avoidance Beliefs Questionnaire (FABQ)] and 2,727 patients with acute LBP completed a self-administered questionnaire assessing pain, perceived handicap and disability (on the Quebec Back Pain Disability Scale) and fear-avoidance beliefs (on the FABQ). RESULTS: Patients' FABQ mean scores were 16.8+/-5.0 for physical activities (FABQ Physical) and 19.5+/-10.9 for occupational activities (FABQ Work). From multivariate analysis, the following factors were associated with patients' FABQ Phys and Work scores: having a GP with a high rating on the FABQ Phys (P=0.0001 and 0.02 for FABQ Phys and Work, respectively), no sport practice (vs. occasional: P=0.0003 and 0.03; vs. usual/competition: P=0.0001 and 0.004), disability score (Quebec) (P=0.0001 for both FABQ scores), and pain intensity (P=0.0012 and 0.0013). CONCLUSIONS: High levels of fear-avoidance beliefs occur early in LBP patients, and key messages on this topic should probably be delivered at a very early stage of the disease.

International audience; INTRODUCTION: The term of "migralepsy" has been proposed to define migraine-triggered epileptic seizures. Although already reported in the literature for more than fifty years, a number of observations remain debatable because of possible confusion between migraine and epileptic seizure clinical manifestations, including hemifield visual hallucinations, digestive signs and severe headache. OBSERVATION: We report on the case of a young patient suffering from both diseases, in whom a visual aura preceded either migraine attacks or epileptic generalized tonic-clonic seizure. Subtle modification in the primitive visual hallucination, which suddenly contained colored figures and was accompanied by fear before a prolonged loss of contact, suggested a continuum between migraine aura and epileptic seizure in this patient. Brain MRI was normal and EEG showed some sharp waves in the right posterior area. CONCLUSION: The presence of a neurophysiological continuum between migrainous aura and epileptic seizure is supported by this observation of "migralepsy". Recent findings from genetic and epidemiological studies further support this link.

The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx) are thought to promote arousal through the excitatory action they exert on the multiple areas to which they project within the CNS. We show here that the hcrt/orx peptides can also exert a strong action on the amygdala, a structure known for its implication in emotional aspects of behavior. Indeed, the hcrt/orx peptides, applied in acute rat brain slices, excite a specific class of "low threshold burst" neurons in the central medial (CeM) nucleus which is considered as a major output of the amygdala. These excitatory effects are postsynaptic, mediated by Hcrt2/OX2 receptors and result from the closure of a potassium conductance. They occur on a class of neurons that are also excited by vasopressin acting through V1a receptors. These results suggest that the hcrt/orx system can act through the amygdala to augment arousal and evoke the autonomic and behavioral responses associated with fear, stress or emotion.

International audience; Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory.

International audience; Memory consolidation refers to a process by which newly learned information is made resistant to disruption. Traditionally, consolidation has been viewed as an event that occurs once in the life of a memory. However, considerable evidence now indicates that consolidated memories, when reactivated through retrieval, become labile (susceptible to disruption) again and undergo reconsolidation. Because memories are often interrelated in complex associative networks rather than stored in isolation, a key question is whether reactivation of one memory makes associated memories labile in a way that requires reconsolidation. We tested this in rats by creating interlinked associative memories using a second-order fear-conditioning task. We found that directly reactivated memories become labile, but indirectly reactivated (i.e., associated) memories do not. This suggests that memory reactivation produces content-limited rather than wholesale changes in a memory and its associations and explains why each time a memory is retrieved and updated, the entire associative structure of the memory is not grossly altered.

International audience; In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological manipulation of intracellular signaling pathways. In the first experiment, rats were given intrathalamic infusions of the MEK (mitogen-activated protein kinase-kinase) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126) before fear conditioning. Findings revealed that long-term memory (assessed at 24 h) was impaired, whereas short-term memory (assessed at 1-3 h) of fear conditioning was intact. In the second experiment, rats received immediate posttraining intrathalamic infusion of U0126, the mRNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), or infusion of the protein synthesis inhibitor anisomycin. Posttraining infusion of either U0126 or DRB significantly impaired long-term retention of fear conditioning, whereas infusion of anisomycin had no effect. In the final experiment, rats received intrathalamic infusion of U0126 before long-term potentiation (LTP)-inducing stimulation of thalamic inputs to the lateral nucleus of the amygdala (LA). Findings revealed that thalamic infusion of U0126 impaired LTP in the LA. Together, these results suggest the possibility that MGm/PIN cells that project to the LA contribute to memory formation via ERK (extracellular signal-regulated kinase)-mediated transcription, but that they do so by promoting protein synthesis-dependent plasticity locally in the LA.

The Journal recently published two studies suggesting a specific increase in the number of ventricular arrhythmias in implantable defibrillator patients in the weeks following the World Trade Center (WTC) attack of September 11, 2001 (9/11), both in patients living near or geographically distant

International audience; RGS proteins are negative regulators of signaling through heterotrimeric G protein-coupled receptors and, as such, are in a position to regulate a plethora of biological phenomena. However, those have just begun to be explored in vivo. Here, we describe a mouse line deficient for Rgs4, a gene normally expressed early on in discrete populations of differentiating neurons and later on at multiple sites of the central nervous system, the cortex in particular, where it is one of the most highly transcribed Rgs genes. Rgs4(lacZ/lacZ) mice had normal neural development and were viable and fertile. Behavioral testing on mutant adults revealed subtle sensorimotor deficits but, so far, supported neither the proposed status of Rgs4 as a schizophrenia susceptibility gene (by showing intact prepulse inhibition in the mutants) nor (unlike another member of the Rgs family, Rgs9) a role of Rgs4 in the acute or chronic response to opioids.

International audience; Of all the psychological complications that an individual is likely to present with when confronted with an exceptional event, the Post-Traumatic Stress Disorder is characterized by being progressive, frequent, invalidating, strongly associated with comorbidity, and having the tendency to become chronic if it is not detected clinically. By definition, it is threatening and produces an intense fear reaction. The traumatic event is a situation of extreme stress, not only capable of altering the physical and psychological homeostasis of the individual, but is also recognized as determinant in the aetiopathology of complications. The intensity of this distress can be identified clinically and physiologically, and is currently considered as an important risk factor for the development of PTSD later on, together with other pre-, peri- and post-traumatic factors. In fact, the most studied field is the therapeutic approach, in particular drug treatment, of the fully-constituted disorder, although this actually represents tertiary prevention. Even though primary prevention seems to concern Medicine very little, any prospect of performing secondary prevention should begin by rapid identification of the risk or vulnerability factors and should allow a population at risk from developing complications to be defined. Its potential therapeutic impact brings together psychotherapeutic and drug treatment, since it is only this combination that seems able to allow the most favourable clinical outcome to be achieved for an individual, who is confronted by an out-of-the-ordinary event. The aims of secondary prevention strategies are, for example, to reduce the incidence of acute PTSD in patients seen following the event. The benefits for the individual and for the society can easily be measured in terms of the consequences on his/her social, professional and family life, or in terms of cost. The usefulness of this prevention can also be measured by the possible ways that other conditions, comorbid to PTSD, are controlled, such as anxiety disorders, depression and substance abuse, for example. Secondary prevention strategies may also be aimed at determining the therapeutic impact, by preventing or moderating the appearance of an acute stress, or even by contributing in avoiding the onset of chronic PTSD. Psychopharmacology of the immediate and post-immediate disorders, however, remains a field which has been studied very little. Reduction or control of the high, prolonged level of hyperarousal phenomena or hypersensitization of the hypothalamo-pituitary axis, would contribute to the comfort of the individual, and would participate in the prevention of PTSD. Based on current knowledge of the neurobiology of trauma, we look into the existing and potential pharmacological possibilities. Even though benzodiazepines tend to have an important role, knowledge of other drugs and therapeutic groups is rapidly increasing. In this review, we will see that the efficacy of anti-adrenergic drugs and certain other anxiolytics is now well-documented, this opening the door to their use in the future. Other drug groups offer interesting, well-proven approaches, such as serotoninergic drugs, CRF or NPY antagonists, NMDA antagonists, anticonvulsants or other GABAergic agents. In view of this disorder, which represents a true public health problem, we consider that it is now possible to widen the horizons of our drug therapy, in combination with any necessary psychotherapeutic treatment, to reach the heart of the traumatic event, that often upsets the victims, both by the psychological suffering it induces, and the loss of his/her social, family and professional references and support structures.

Objective: We prospectively examined the relation between various peritraumatic responses (that is, fear, helplessness, horror, amnesia, and fright) and the development of posttraumatic stress disorder (PTSD) 2 months after a trauma. Method: Participants included 123 motor vehicle accident (MVA) victims consecutively hospitalized in a traumatology department for over 72 hours during a 16-month period. Between day 2 and day 5 of their hospitalization, a psychiatrist assessed the patients' peritraumatic responses and acute stress disorder (ASD). Two months after the accident, an experienced psychiatrist contacted the patients by telephone, and the PTSD symptoms and the diagnosis were assessed with a modified version of the Clinician-Administered PTSD Scale (CAPS). Results: Of the participants, 48 reported an immediate fright reaction when faced with the prospect of their own death. Participants who reported a fright experience had a 17 times greater risk of subsequently meeting the diagnostic criteria for PTSD (odds ratio 16.75). A fright reaction predicted PTSD development with a specificity of 0.93 and a sensitivity of 0.60. Conclusion: The immediate reactions described in criterion A2 of the DSM-IV (that is, fear, helplessness, and horror) did not seem to be equally relevant. An initial feeling of fright seems to be an essential qualitative factor in the clinical description of psychological trauma.

International audience; The effects of ibotenic lesions of the hippocampus on conditioning to contextual cues during classical fear conditioning in rats were evaluated by (a) the amount of freezing elicited by contextual cues and (b) the relative avoidance of a shock compartment. In Experiment 1, lesions to the hippocampus had no effect on contextual freezing and marginally affected avoidance after repeated sessions. Experiment 2 showed that lesions to the hippocampus disrupted avoidance when tested after a single conditioning session, while leaving unaffected the acquisition of contextual freezing. Experiment 3 indicated that these lesions decreased the acquisition of contextual freezing when higher footshock intensity was used but had no effect on avoidance after repeated conditioning sessions. These results show that freezing and avoidance do not quantify context conditioning similarly. They further indicate that lesions to the hippocampus may disrupt the expression of these behaviors used as measures of context conditioning but not the acquisition of context conditioning per se.

International audience; Genetic factors have been shown to influence the nature and the intensity of the stress responses. In order to understand better the genetic mechanisms involved, we have studied the behavioral and neuroendocrine responses to novel environments in the WKHA/WKY inbred strains and we have investigated the genetic relationships between these traits in a segregating F2 intercross. The animals were submitted to behavioral tests known to provide both indices of activity and fear (activity cages, open field and elevated plus-maze). The plasma levels of prolactin, ACTH, corticosterone, glucose and renin activity were determined after a 10-min exposure to novelty. Our results showed that WKHA rats, compared to WKYs, were more active in a familiar as well as in novel environments. They exhibited also less anxiety-related behaviors and lower neuroendocrine responses. A principal component analysis performed on the behavioral F2 results defined three independent factors: general activity, anxiety and defecation, none of them being correlated with the neuroendocrine measures. Thus this study suggests that these different responses to stress are independent components that may have distinct molecular bases.

International audience; BACKGROUND: It is well known that facial expressions represent important social cues. In humans expressing facial emotion, fear may be configured to maximize sensory exposure (e.g., increases visual input) whereas disgust can reduce sensory exposure (e.g., decreases visual input). To investigate whether such effects also extend to the attentional system, we used the "attentional blink" (AB) paradigm. Many studies have documented that the second target (T2) of a pair is typically missed when presented within a time window of about 200-500 ms from the first to-be-detected target (T1; i.e., the AB effect). It has recently been proposed that the AB effect depends on the efficiency of a gating system which facilitates the entrance of relevant input into working memory, while inhibiting irrelevant input. Following the inhibitory response on post T1 distractors, prolonged inhibition of the subsequent T2 is observed. In the present study, we hypothesized that processing facial expressions of emotion would influence this attentional gating. Fearful faces would increase but disgust faces would decrease inhibition of the second target. METHODOLOGY/PRINCIPAL FINDINGS: We showed that processing fearful versus disgust faces has different effects on these attentional processes. We found that processing fear faces impaired the detection of T2 to a greater extent than did the processing disgust faces. This finding implies emotion-specific modulation of attention. CONCLUSIONS/SIGNIFICANCE: Based on the recent literature on attention, our finding suggests that processing fear-related stimuli exerts greater inhibitory responses on distractors relative to processing disgust-related stimuli. This finding is of particular interest for researchers examining the influence of emotional processing on attention and memory in both clinical and normal populations. For example, future research could extend upon the current study to examine whether inhibitory processes invoked by fear-related stimuli may be the mechanism underlying the enhanced learning of fear-related stimuli.

International audience