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Background: Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi Syndrome (PWS). Clinical evidence suggests aberrant pro-social behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, what neuronal mechanisms underlie impaired behavioral responses in a socially-aversive context, and how can they be corrected, remains largely unknown. Methods: Using the Magel2 knocked-out (KO) mouse model of PWS (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological and pharmacological strategies in a social-fear-conditioning paradigm. Pathway specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region which receives dense hypothalamic inputs. Results: OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, which failure in Magel2KO mice disinhibited somatostatin (SST) neurons and disrupted social-fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleusâLS pathway of Magel2KO mice disrupting social-fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST-neurons in the LS. Interestingly, LS SST-neurons also gated the expression of aggressive behavior, possibly as part of functional units operating beyond local septal circuits. Conclusions: SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially-aversive context, and provides a new framework for future treatments in autism-spectrum disorders.
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Modelos Animales de Enfermedad , Extinción Psicológica , Miedo , Ratones Noqueados , Neuronas , Oxitocina , Síndrome de Prader-Willi , Somatostatina , Vasopresinas , Animales , Oxitocina/farmacología , Somatostatina/farmacología , Somatostatina/metabolismo , Miedo/efectos de los fármacos , Miedo/fisiología , Extinción Psicológica/efectos de los fármacos , Extinción Psicológica/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratones , Síndrome de Prader-Willi/fisiopatología , Síndrome de Prader-Willi/tratamiento farmacológico , Vasopresinas/metabolismo , Agresión/efectos de los fármacos , Agresión/fisiología , Masculino , Conducta Social , Núcleos Septales/efectos de los fármacos , Núcleos Septales/metabolismo , Optogenética , Ratones Endogámicos C57BL , Péptidos y Proteínas de Señalización Intracelular , Proteínas Intrínsecamente DesordenadasRESUMEN
The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders.
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Social anxiety disorder is a common psychiatric condition that severely affects quality of life of individuals and is a significant societal burden. Although many risk factors for social anxiety exist, it is currently unknown how social fear sensitivity manifests biologically. Furthermore, since some individuals are resilient and others are susceptible to social fear, it is important to interrogate the mechanisms underpinning individual response to social fear situations. The microbiota-gut-brain axis has been associated with social behaviour, has recently been linked with social anxiety disorder, and may serve as a therapeutic target for modulation. Here, we assess the potential of this axis to be linked with social fear extinction processes in a murine model of social anxiety disorder. To this end, we correlated differential social fear responses with microbiota composition, central gene expression, and immune responses. Our data provide evidence that microbiota variability is strongly correlated with alterations in social fear behaviour. Moreover, we identified altered gene candidates by amygdalar transcriptomics that are linked with social fear sensitivity. These include genes associated with social behaviour (Armcx1, Fam69b, Kcnj9, Maoa, Serinc5, Slc6a17, Spata2, and Syngr1), inflammation and immunity (Cars, Ckmt1, Klf5, Maoa, Map3k12, Pex5, Serinc5, Sidt1, Spata2), and microbe-host interaction (Klf5, Map3k12, Serinc5, Sidt1). Together, these data provide further evidence for a role of the microbiota-gut-brain axis in social fear responses.
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Eje Cerebro-Intestino , Extinción Psicológica , Miedo , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Miedo/fisiología , Ratones , Microbioma Gastrointestinal/fisiología , Extinción Psicológica/fisiología , Masculino , Eje Cerebro-Intestino/fisiología , Encéfalo/metabolismo , Conducta Social , Fobia Social/metabolismo , Fobia Social/psicología , Amígdala del Cerebelo/metabolismo , Modelos Animales de Enfermedad , Ansiedad/metabolismoRESUMEN
In mammals, some physiological conditions are associated with the high brain oxytocin (OXT) system activity. These include lactation in females and mating in males and females, both of which have been linked to reduced stress responsiveness and anxiolysis. Also, in a murine model of social fear conditioning (SFC), enhanced brain OXT signaling in lactating mice, specifically in the lateral septum (LS), was reported to underlie reduced social fear expression. Here, we studied the effects of mating in male mice on anxiety-related behaviour, social (and cued) fear expression and its extinction, and the activity of OXT neurons reflected by cFos expression and OXT release in the LS and amygdala. We further focused on the involvement of brain OXT in the mating-induced facilitation of social fear extinction. We could confirm the anxiolytic effect of mating in male mice irrespective of the occurrence of ejaculation. Further, we found that only successful mating resulting in ejaculation (Ej+) facilitated social fear extinction, whereas mating without ejaculation (Ej-) did not. In contrast, mating did not affect cues fear expression. Using the cellular activity markers cFos and pErk, we further identified the ventral LS (vLS) as a potential region participating in the effect of ejaculation on social fear extinction. In support, microdialysis experiments revealed a rise in OXT release within the LS, but not the amygdala, during mating. Finally, infusion of an OXT receptor antagonist into the LS before mating or into the lateral ventricle (icv) after mating demonstrated a significant role of brain OXT receptor-mediated signaling in the mating-induced facilitation of social fear extinction.
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Amígdala del Cerebelo , Extinción Psicológica , Miedo , Oxitocina , Conducta Sexual Animal , Animales , Miedo/fisiología , Oxitocina/metabolismo , Masculino , Extinción Psicológica/fisiología , Ratones , Femenino , Conducta Sexual Animal/fisiología , Amígdala del Cerebelo/metabolismo , Conducta Social , Ansiedad/metabolismo , Receptores de Oxitocina/metabolismo , Núcleos Septales/metabolismo , Núcleos Septales/efectos de los fármacos , Eyaculación/fisiología , Copulación/fisiología , Tabique del Cerebro/metabolismo , Tabique del Cerebro/fisiología , Ratones Endogámicos C57BL , Conducta Animal/fisiología , Conducta Animal/efectos de los fármacosRESUMEN
Previous studies showed that the dorsal premammillary nucleus of the hypothalamus (PMD) is involved in social passive defensive behaviors likely to be meditated by descending projections to the periaqueductal gray (PAG). We focused on the rostral dorsomedial PAG (rPAGdm) to reveal its putative neural mechanisms involved in mediating social defensive responses. By combining retrograde tracing and FOS expression analysis, we showed that in addition to the PMD, the rPAGdm is influenced by several brain sites active during social defeat. Next, we found that cytotoxic lesions of the rPAGdm drastically reduced passive defense and did not affect active defensive responses. We then examined the rPAGdm's projection pattern and found that the PAGdm projections are mostly restricted to midbrain sites, including the precommissural nucleus, different columns of the PAG, and the cuneiform nucleus (CUN). Also, we found decreased FOS expression in the caudal PAGdm, CUN, and PMD after the rPAGdm was lesioned. The results support that the rPAGdm mediates passive social defensive responses through ascending paths to prosencephalic circuits likely mediated by the CUN. This study provides further support for the role of the PAG in the modulation of behavioral responses by working as a unique hub for influencing prosencephalic sites during the mediation of aversive responses.
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Sustancia Gris Periacueductal , Derrota Social , Ratas , Animales , Sustancia Gris Periacueductal/fisiología , Hipotálamo/fisiologíaRESUMEN
BACKGROUND: Alcohol use disorder (AUD) is a significant public health problem. A better understanding of the psychosocial factors contributing to AUD is important for developing public health policy. The purpose of this study was to identify social mechanisms involved in AUD and, more specifically, to determine whether vicarious learning deficits are related to the disorder. A secondary objective was to evaluate the role of empathy in social fear conditioning. METHODS: Patients with severe AUD (n = 30) and healthy participants (n = 30) performed a social fear learning (SFL) task. The task assesses how an association between a stimulus and an aversive consequence is acquired through social means. Specifically, participants observed a person receiving an electric shock (unconditioned stimulus; US) that was associated (conditioned stimulus; CS+) or not (CS-) with a neutral CS. The skin conductance response was used to measure the effect of learning. RESULTS: Individuals with severe AUD showed a deficit in SFL, indicating that they had difficulty learning from another's negative experience. Patients also evaluated the emotional experience as less unpleasant than healthy participants. CONCLUSIONS: This study is the first to show that patients with severe AUD have social learning deficits. The findings suggest that these individuals do not learn from another's negative experience. At a fundamental level, the findings demonstrate the importance of understanding the role of social mechanisms in AUD. At a clinical level, the study highlights the potential for using social learning enhancement to prevent relapse in individuals with severe AUD.
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This study examined longitudinal relations between attention and social fear across the first two years of life. Our sample consisted of 357 infants and their caregivers across three sites. Data was collected at 4, 8, 12, 18, and 24 months of age. At all 5 assessments, the infants participated in 2 eye-tracking tasks (Vigilance and Overlap) which measured different components of attention bias (orientation, engagement, and disengagement), and parents completed questionnaires assessing infant temperament. For the first three assessments, social fear was measured using the Infant Behavioral Questionnaire-Revised (IBQ-R; Gartstein & Rothbart, 2003) focused on interactions with strangers, and for the final two time points, we used the social fearfulness subscale on the Toddler Behavior Assessment Questionnaire (TBAQ; Goldsmith, 1996). The results of a random intercept cross-lagged panel model showed intermittent evidence of uni-directional and reciprocal relations between attention to both threatening and positive emotion facial configurations and social fear. Our findings suggest that characteristics of behaviorally inhibited temperament-in this case, social fear-begin to interact with attention biases to emotion in the very first year of life, which carries implications for the timing of future interventions designed to mitigate the early development of maladaptive patterns of attention.
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Miedo , Temperamento , Lactante , Humanos , Miedo/psicología , Emociones , Encuestas y Cuestionarios , PadresRESUMEN
Elevated social fear in infancy poses risk for later social maladjustment and psychopathology. Hair cortisol concentration (HCC), an index of cumulative cortisol exposure, and diurnal salivary cortisol slope, a biomarker of acute stress regulation, have been associated with social fear behaviors in childhood; however, no research has addressed their relations in infancy. Elucidating potential biomarkers of infant social fear behaviors, as well as environmental factors associated with these biomarkers, may grant insights into the ontogeny of fear behaviors that increase risk for internalizing and externalizing psychopathologies later in life. The current study used multiple linear regression to examine if infant HCC, infant diurnal cortisol slope, and income-to-needs ratios (ITN) were differentially associated with observed social fear responses to a Stranger Approach task at 12 months. Using a sample of 90 infants (Mage = 12.26m, SD = 0.81m, 50% female), results indicated that increased infant HCC was associated with increased distress vocalizations during the Stranger Approach task, while steeper diurnal cortisol slope was associated with fewer distress vocalizations. Ordinary least squares path analyses did not reveal group differences between economically strained and non-strained infants in how cortisol measures and social fear responses related. Findings underscore very early psychobiological correlates of fearfulness that may increase risk for fear-related disorders and adverse mental health symptomology across childhood.
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Hidrocortisona , Saliva , Niño , Miedo , Femenino , Cabello/química , Humanos , Lactante , Masculino , Saliva/química , Estrés PsicológicoRESUMEN
Parental verbal threat (vs. safety) information regarding the social world may impact a child's fear responses, evident in subjective, behavioral, cognitive, and physiological indices of fear. In this study, primary caregivers provided standardized verbal threat or safety information to their child (N = 68, M = 5.27 years; 34 girls) regarding two strangers in the lab. Following this manipulation, children reported fear beliefs for each stranger. Physiological and behavioral reactions were recorded as children engaged with the two strangers (who were blind to their characterization) in a social interaction task. Child attention to the strangers was measured in a visual search task. Parents also reported their own, and their child's, social anxiety symptoms. Children reported more fear for the stranger paired with threat information, but no significant differences were found in observed child fear, attention, or heart rate. Higher social anxiety symptoms on the side of the parents and the children exacerbated the effect of parental verbal threat on observed fear. Our findings reveal a causal influence of parental verbal threat information only for child-reported fear and highlight the need to further refine the conditions under which acquired fear beliefs persist and generalize to behavior/physiology or get overruled by nonaversive real-life encounters.
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Aprendizaje Social , Miedo/psicología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Padres/psicologíaRESUMEN
Social avoidance in rodents arises from a complex interplay between the prefrontal cortex and subcortical structures, such as the ventromedial hypothalamus and the dorsal periaqueductal gray matter. Experimental studies are revealing the contribution of these areas, but an integrative view and model of how they interact to produce adaptive behavior are still lacking. Here, we present a computational model of social avoidance, proposing a set of integrated hypotheses on the possible macro organization of the brain system underlying this phenomenon. The model is validated by accounting for several different empirical findings and produces predictions to be tested in future experiments.
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Face masks are now seen as a key tool in the world's recovery from the COVID-19 pandemic. However, during the early stages of the outbreak, face mask use in the United Kingdom (UK) was significantly lower than that of countries equally impacted by the virus. We were interested to explore whether social cognitions played a role in levels of mask wearing. A cross-sectional online survey of UK adults (n=908) was conducted in July 2020. Estimated face mask use and thoughts about wearing face masks were assessed using measures developed for this study. Participants also answered questions about their general mood, social anxiety and basic demographic data. Multiple regression was used to examine factors associated with mask wearing. Participants' estimated mask wearing was low when in public spaces, such as the park (17%) or walking on the high street (36%). However, broadly fitting with UK guidance at the time, rates were considerably higher when in situations of closer proximity to others, such as on public transport (94%), in a shop or café (62%), when speaking to somebody in an enclosed public space (67%) or in a busy area when social distancing was not possible (79%). When looking at estimated mask wearing when in proximity to others, positive social cognitions (e.g., I'll look confident and competent wearing a mask) were associated with more wearing, whereas negative social cognitions (e.g., I'll look anxious, I'll look foolish) were associated with less wearing. These results remained after controlling for factors that have indicated increased risk from COVID-19 (age, gender, ethnicity, presence of a health condition or pregnancy), belief about the health benefit for others and levels of depression and social anxiety. The largest predictors of mask wearing were the amount of people believed wearing a mask would keep others safe and the presence of an underlying health condition. The study findings indicate that future public health campaigns would benefit from a focus on strengthening beliefs about the protective benefits of masks, but also promoting positive social messages about wearing in public (e.g., mask wearing means you are confident and competent).
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Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We previously showed that intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC) and localized these effects to the dorsolateral septum (DLS) and central amygdala (CeA). In the present study, we aimed to identify the receptor subtypes that mediate these local effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduced the expression of SFC-induced social fear in a brain region- and receptor-specific manner in male mice. In the DLS, NPY reduced the expression of social fear by acting on Y2 receptors but not on Y1 receptors. As such, prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 µL/side) but not the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 µL/side) blocked the effects of NPY in the DLS. In the CeA, however, BIBO3304 trifluoroacetate but not BIIE0246 blocked the effects of NPY, suggesting that NPY reduced the expression of social fear by acting on Y1 receptors but not Y2 receptors within the CeA. This study suggests that at least two distinct receptor subtypes are differentially recruited in the DLS and CeA to mediate the effects of NPY on the expression of social fear.
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Amígdala del Cerebelo/metabolismo , Neuropéptido Y/metabolismo , Fobia Social/metabolismo , Tabique del Cerebro/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Animales , Arginina/análogos & derivados , Arginina/farmacología , Benzazepinas/farmacología , Miedo , Masculino , Ratones , Fobia Social/fisiopatología , Receptores de Neuropéptido Y/metabolismo , Tabique del Cerebro/efectos de los fármacosRESUMEN
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that the intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC). In the present study, we aimed to identify the brain regions that mediate these effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduces the expression of SFC-induced social fear in a brain-region-dependent manner. In more detail, NPY reduced the expression of social fear when administered into the dorsolateral septum (DLS) and central amygdala (CeA), but not when administered into the dorsal hippocampus (DH), medial amygdala (MeA) and basolateral amygdala (BLA). We also investigated whether the reduced expression of social fear might partly be due to a reduced anxiety-like behavior, and showed that NPY exerted anxiolytic-like effects when administered into the DH, DLS, CeA and BLA, but not when administered into the MeA. This study identifies the DLS and the CeA as brain regions mediating the effects of NPY on the expression of social fear and suggests that partly distinct neural circuitries mediate the effects of NPY on the expression of social fear and on anxiety-like behavior.
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Ansiedad/metabolismo , Encéfalo/metabolismo , Neuropéptido Y/metabolismo , Animales , Masculino , Ratones , Neuropéptido Y/administración & dosificaciónRESUMEN
Accumulating evidence indicates that the central orexin (hypocretin) system plays an important role in regulating emotional processes in both humans and rodents. Thus, the orexin system has been repeatedly implicated in the pathophysiology of several neuropsychiatric disorders, such as anxiety disorders. Among others, symptoms like social fear and social withdrawal are frequently observed in these disorders. Based on this, we investigated the role of orexin deficiency in social (fear) behavior. For that, female and male orexin-deficient mice were tested for (1) sociability and social novelty, and (2) acquisition, expression, and extinction of conditioned social fear. We found that female orexin-deficient mice displayed reduced sociability and decreased preference for social novelty compared to their wild-type littermates. These effects of orexin deficiency were not observed in males. Moreover, orexin deficiency facilitated the acquisition and/or expression of conditioned social fear and impaired the extinction of social fear in both sexes. Taken together, our results indicate an important, partly sex-dependent, regulatory role of the orexin system in social (fear) behavior. Our findings support the hypothesis of orexin being an integrator of motivation, affect, and emotion.
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Extinción Psicológica/efectos de los fármacos , Miedo/fisiología , Orexinas/metabolismo , Animales , Ansiedad/fisiopatología , Trastornos de Ansiedad/fisiopatología , Condicionamiento Operante , Señales (Psicología) , Extinción Psicológica/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Orexinas/deficiencia , Orexinas/genética , Conducta SocialRESUMEN
In many social anxiety disorder (SAD) patients, the efficacy of antidepressant therapy is unsatisfactory. Here, we investigated whether mice deficient for the lysosomal glycoprotein acid sphingomyelinase (ASM-/-) represent an appropriate tool to study antidepressant-resistant social fear. We also investigated whether neuropeptide Y (NPY) reduces this antidepressant-resistant social fear in ASM-/- mice, given that NPY reduced social fear in a mouse model of SAD, namely social fear conditioning (SFC). We show that neither chronic paroxetine nor chronic amitriptyline administration via drinking water were successful in reducing SFC-induced social fear in ASM-/- mice, while the same treatment reduced social fear in ASM+/- mice and completely reversed social fear in ASM+/+ mice. This indicates that the antidepressants paroxetine and amitriptyline reduce social fear via the ASM-ceramide system and that ASM-/- mice represent an appropriate tool to study antidepressant-resistant social fear. The intracerebroventricular administration of NPY, on the other hand, reduced social fear in ASM-/- mice, suggesting that NPY might represent an alternative pharmacotherapy for antidepressant-resistant social fear. These results suggest that medication strategies aimed at increasing brain NPY concentrations might improve symptoms of social fear in SAD patients who fail to respond to antidepressant treatments.
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Antidepresivos/uso terapéutico , Resistencia a Medicamentos , Miedo/efectos de los fármacos , Neuropéptido Y/uso terapéutico , Fobia Social/tratamiento farmacológico , Animales , Condicionamiento Clásico/efectos de los fármacos , Resistencia a Medicamentos/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Noqueados , Neuropéptido Y/farmacología , Paroxetina/farmacología , Paroxetina/uso terapéutico , Receptores de Neuropéptido Y/agonistas , Esfingomielina Fosfodiesterasa/genéticaRESUMEN
The nonapeptide, oxytocin (OT), known for its role in social bonding and attachment formation, has demonstrated anxiolytic properties in animal models and human studies. However, its role in the regulation of fear responses appears more complex, brain site-specific, sex-specific, and dependent on a prior stress history. Studies have shown that OT neurons in the hypothalamus are activated during cued and contextual fear conditioning and during fear recall, highlighting the recruitment of endogenous oxytocin system in fear learning. OT is released into the extended amygdala, which contains the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), both critical for the regulation of fear and anxiety-like behaviors. Behavioral studies report that OT in the CeA reduces contextual fear responses; whereas in the BNST, OT receptor (OTR) neurotransmission facilitates cued fear and reduces fear responses to un-signaled, diffuse threats. These ostensibly contrasting behavioral effects support growing evidence that OT works to promote fear discrimination by reducing contextual fear or fear of diffuse threats, yet strengthening fear responses to imminent and predictable threats. Recent studies from the basolateral nucleus of the amygdala (BLA) support this notion and show that activation of OTR in the BLA facilitates fear discrimination by increasing fear responses to discrete cues. Also, OTR transmission in the CeA has been shown to mediate a switch from passive freezing to active escape behaviors in confrontation with an imminent, yet escapable threat but reduce reactivity to distant threats. Therefore, OT appears to increase the salience of relevant threat-signaling cues yet reduce fear responses to un-signaled, distant, or diffuse threats. Lastly, OTR signaling has been shown to underlie emotional discrimination between conspecifics during time of distress, social transmission of fear, and social buffering of fear. As OT has been shown to enhance salience of both positive and negative social experiences, it can also serve as a warning system against potential threats in social networks. Here, we extend the social salience hypothesis by proposing that OT enhances the salience of relevant environmental cues also in non-social contexts, and as such promotes active defensive behaviors.
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BACKGROUND: Recent theories have linked autism to challenges in prediction learning and social cognition. It is unknown, however, how autism affects learning about threats from others "demonstrators" through observation, which contains predictive learning based on social information. The aims of this study are therefore to investigate social fear learning in individual with autism spectrum disorder (ASD) and to examine whether typically developing social cognition is necessary for successful observational learning. METHODS: Adults with ASD (n = 23) and neurotypical controls (n = 25) completed a social fear learning (SFL) procedure in which participants watched a "demonstrator" receiving electrical shocks in conjunction with a previously neutral conditioned stimulus (CS+), but never with a safe control stimulus (CS-). Skin conductance was used to measure autonomic responses of learned threat responses to the CS+ versus CS-. Visual attention was measured during learning using eye tracking. To establish a non-social learning baseline, each participant also underwent a test of Pavlovian conditioning. RESULTS: During learning, individuals with ASD attended less to the demonstrator's face, and when later tested, displayed stronger observational, but not Pavlovian, autonomic indices of learning (skin conductance) compared to controls. In controls, both higher levels of attention to the demonstrator's face and trait empathy predicted diminished expressions of learning during test. LIMITATIONS: The relatively small sample size of this study and the typical IQ range of the ASD group limit the generalizability of our findings to individuals with ASD in the average intellectual ability range. CONCLUSIONS: The enhanced social threat learning in individuals with ASD may be linked to difficulties using visual attention and mental state attributions to downregulate their emotion.
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Trastorno del Espectro Autista/psicología , Miedo/fisiología , Aprendizaje Social , Adulto , Estudios de Casos y Controles , Condicionamiento Clásico , Electrochoque , Empatía , Movimientos Oculares , Tecnología de Seguimiento Ocular , Femenino , Respuesta Galvánica de la Piel , Humanos , MasculinoRESUMEN
It is well known that long-term consolidation of newly acquired information, including information related to social fear, require de novo protein synthesis. However, the temporal dynamics of protein synthesis during the consolidation of social fear memories is unclear. To address this question, mice received a single systemic injection with the protein synthesis inhibitor, anisomycin, at different time-points before or after social fear conditioning (SFC), and memory was assessed 24 h later. We showed that anisomycin impaired the consolidation of social fear memories in a time-point-dependent manner. Mice that received anisomycin 20 min before, immediately after, 6 h, or 8 h after SFC showed reduced expression of social fear, indicating impaired social fear memory, whereas anisomycin caused no effects when administered 4 h after SFC. These results suggest that consolidation of social fear memories requires two stages of protein synthesis: (1) an initial stage starting during or immediately after SFC, and (2) a second stage starting around 6 h after SFC and lasting for at least 5 h.
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Anisomicina/farmacología , Miedo/efectos de los fármacos , Memoria/efectos de los fármacos , Biosíntesis de Proteínas/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/farmacología , Animales , Anisomicina/administración & dosificación , Condicionamiento Clásico/efectos de los fármacos , Masculino , Ratones , Inhibidores de la Síntesis de la Proteína/administración & dosificación , Factores de TiempoRESUMEN
Animals can use social information to detect threat in the environment. In particular, social learning allows animals to learn about dangers without incurring in the costs of trial-and-error learning. In zebrafish, both chemical and visual social cues elicit an innate alarm response, which consists of erratic movement followed by freezing behavior. Injured zebrafish release an alarm substance from their skin that elicits the alarm response. Similarly, the sight of conspecifics displaying the alarm response can also elicit the expression of this response in observers. In this study, we investigated if these social cues of danger can also be used by zebrafish as unconditioned stimulus (US) in learning. We found that only the chemical cue was effective in the social fear conditioning. We suggest that this differential efficacy of social cues results from the fact that the alarm cue is a more reliable indicator of threat, than the sight of an alarmed conspecific. Therefore, although multiple social cues may elicit innate responses not all have been evolutionarily co-opted to act as US in associative learning. Furthermore, the use of the expression of the immediate early genes as markers of neuronal activity showed that chemical social fear conditioning is paralleled by a differential activation of the olfactory bulbs and by a different pattern of functional connectivity across brain regions involved in olfactory processing.
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Encéfalo/metabolismo , Señales (Psicología) , Miedo , Aprendizaje , Percepción Olfatoria , Conducta Social , Animales , Encéfalo/fisiología , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Percepción Visual , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Being cautious of unfamiliar conspecifics is adaptive because sick or aggressive conspecifics may jeopardize survival and well-being. However, prolonged or excessive caution, i.e. fear related to social situations, is maladaptive and may result in social anxiety disorder. Some anxiety disorders in humans are associated with polymorphisms of the neuropeptide S receptor (NPSR) gene. In line with this finding, animal studies showed an important role of NPS and NPSR in anxiety and fear. The present study investigated the role of NPSR deficiency in social behavior under non-aversive and aversive conditions. For this, female and male NPSR-deficient mice were tested for (1) sociability and social novelty and (2) acquisition, expression, and extinction of conditioned social fear. The present study revealed very particular effects of the NPSR genotype: Sociability was reduced in female heterozygous NPSR-deficient mice, but was unaffected in males and the other genotypes. Furthermore, the NPSR genotype did not affect the acquisition and expression of conditioned social fear, but its extinction was impaired in heterozygous and facilitated in homozygous NPSR-deficient mice. This indicates that the NPS system plays a role in social behavior under non-aversive and aversive conditions, partly in a sex-dependent manner. The present findings may help to explain social symptoms in anxiety disorders associated with the NPSR genotype.