Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and synapses associating conditioned stimuli with aversive events. Hebbian plasticity within these networks requires ...additional reinforcement to store particularly salient experiences into long-term memory. Here we have identified a circuit that reciprocally connects the ventral periaqueductal gray and dorsal raphe region with the central amygdala and that gates fear learning. We found that ventral periaqueductal gray and dorsal raphe dopaminergic (vPdRD) neurons encode a positive prediction error in response to unpredicted shocks and may reshape intra-amygdala connectivity via a dopamine-dependent form of long-term potentiation. Negative feedback from the central amygdala to vPdRD neurons might limit reinforcement to events that have not been predicted. These findings add a new module to the midbrain dopaminergic circuit architecture underlying associative reinforcement learning and identify vPdRD neurons as a critical component of Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal activity may contribute to fear-related psychiatric disorders.
The presentation of a fear memory cue can result in mere memory retrieval, destabilization of the reactivated memory trace, or the formation of an extinction memory. The interaction between the ...degree of novelty during reactivation and previous learning conditions is thought to determine the outcome of a reactivation session. This study aimed to evaluate whether contextual novelty can prevent cue-induced destabilization and disruption of a fear memory acquired by non-asymptotic learning. To this end, fear memory was reactivated in a novel context or in the original context of learning, and fear memory reactivation was followed by the administration of propranolol, an amnestic drug. Remarkably, fear memory was not impaired by post-reactivation propranolol administration or extinction training under the usual conditions used in our lab, irrespective of the reactivation context. These unexpected findings are discussed in the light of our current experimental parameters and alleged boundary conditions on memory destabilization.
Many Indian COVID-19 suicide cases are turning the press-media attention and flooding in the social media platforms although, no particular studies assessed the COVID-19 suicide causative factors to ...a large extent. Therefore, the present study presents 69 COVID-19 suicide cases (aged 19 to 65 years; 63 cases were males). The suicide causalities are included as follows – fear of COVID-19 infection (n=21), followed by financial crisis (n=19), loneliness, social boycott and pressure to be quarantine, COVID-19 positive, COVID-19 work-related stress, unable to come back home due to lockdown, unavailability of alcohol etc. Considering the extreme psychological impacts related to COVID-19, there emerges a need for countrywide extensive tele-mental health care services.
Perceptual constancy requires the brain to maintain a stable representation of sensory input. In the olfactory system, activity in primary olfactory cortex (piriform cortex) is thought to determine ...odour identity
. Here we present the results of electrophysiological recordings of single units maintained over weeks to examine the stability of odour-evoked responses in mouse piriform cortex. Although activity in piriform cortex could be used to discriminate between odorants at any moment in time, odour-evoked responses drifted over periods of days to weeks. The performance of a linear classifier trained on the first recording day approached chance levels after 32 days. Fear conditioning did not stabilize odour-evoked responses. Daily exposure to the same odorant slowed the rate of drift, but when exposure was halted the rate increased again. This demonstration of continuous drift poses the question of the role of piriform cortex in odour perception. This instability might reflect the unstructured connectivity of piriform cortex
, and may be a property of other unstructured cortices.
Objective
Anorexia nervosa (AN) is a pernicious psychiatric disorder which is principally characterized by a fear of weight gain. Notwithstanding the centrality of fear in the psychopathology of AN, ...controlled assessments of negative valence systems are lacking. Herein we assess fear conditioning in adolescent females with AN.
Method
Adolescent girls (Mage = 14.6 years, ±1.57) with DSM‐5 diagnoses of AN (N = 25) and age‐matched control girls (Mage = 14.8 years, ±1.46) with no DSM‐5 diagnoses (N = 25) completed structured clinical interviews and participated in a classical three‐phase Pavlovian fear conditioning paradigm. Participants with comorbid anxiety disorders were excluded. Skin conductance response (SCR) was measured, alongside self‐reported fear, valence, and fear expectancy ratings.
Results
Both groups demonstrated significant differential acquisition across all four measures. Regarding group comparisons, no differences emerged for self‐reported fear, valence, and fear expectancy ratings during acquisition, although for SCR, those with AN demonstrated reduced physiological arousal relative to controls. Both groups demonstrated significant differential extinction for unconditioned stimuli (US) expectancy, self‐report fear, and self‐report valence. No statistically significant group differences were evident during extinction to the conditioned stimuli (CS)+, on any outcome measure. However, controls reported more positive valence to the CS− than those with AN.
Conclusions
Contrary to our hypotheses, our preliminary assessment did not find support for elevated fear responding among adolescent girls with AN with regards to fear acquisition or extinction. These data suggest that AN in adolescent girls may not be associated with a heightened propensity to acquire fear, but conversely, may suggest that exposure treatments for AN may be helpful, since extinction learning is intact in AN.
Public significance
AN is characterized by fear‐related symptoms, including food and weight‐related fear, and behavioral avoidance, yet controlled studies assessing fear learning are limited. Our preliminary assessment of adolescent AN indicates no abnormalities in fear learning among adolescents with AN. These findings may inform existing mechanistic models of AN psychopathology, and the development of exposure‐based treatments for AN.
Eating disorders (EDs) are serious psychiatric illnesses with high mortality and societal cost. Despite their severity, there are few evidence-based treatments, and only 50% of individuals respond to ...existing treatments. This low response rate may be due to the fact that EDs are highly heterogeneous disorders. Precision treatments are needed that can intervene on individual maintenance factors. The first step in such treatment development is identification of central treatment targets, both at the group (i.e., on average) and individual level. The current study (N = 102 individuals with an ED) utilized intensive longitudinal data to model several types of group-level and individual network models. Overall, we identified several group-level central symptoms, with the most common central symptoms of fear of weight gain, desire for thinness, feeling like one is overeating, thinking about dieting, and feeling guilty. We also found that these symptoms, specifically fear of weight gain, a desire to be thinner, thinking about dieting, feeling like one is overeating, and feeling guilty, predicted ED severity at a 1- and 6-month follow-up. We modeled 97 individual networks and found that central symptoms were highly heterogeneous, regardless of ED diagnosis. This work adds to the growing literature using intensive longitudinal data to model ED pathology and implicates fear of weight gain, thinking about dieting, and feelings of guilt as symptoms needing further treatment development work. Additionally, this work contributes essential knowledge on how group and individual network modeling can be used to conceptualize the maintenance of EDs on average and at the individual level.
General Scientific Summary
We used intensive longitudinal data to identify key symptoms of an eating disorder that maintain illness. Using a data-driven method called network analysis, we found that fear of weight gain, thinking about dieting, and guilt are key symptoms and that these symptoms predict eating disorder severity at 1-month and 6-month follow-up. This work also demonstrates how data-driven algorithms may be used to inform selection of personalized treatment targets for individuals with an eating disorder.
•Significant sex differences were seen in a fear-safety-reward discrimination task.•Females did not inhibit conditioned freezing in the presence of a safety cue.•Females showed higher darting levels ...than males.•Females did not show extinction of cued freezing, whereas male rats did.•Females had elevated reward seeking to a reward cue which declined after footshock.
Reward availability and the potential for danger or safety potently regulate emotion. Despite women being more likely than men to develop emotion dysregulation disorders, there are comparatively few studies investigating fear, safety and reward regulation in females. Here, we show that female Long Evans rats did not suppress conditioned freezing in the presence of a safety cue, nor did they extinguish their freezing response, whereas males did both. Females were also more reward responsive during the reward cue until the first footshock exposure, at which point there were no sex differences in reward seeking to the reward cue. Darting analyses suggest females were able to regulate this behavior in response to the safety cue, suggesting they were able to discriminate between fear and safety cues but did not demonstrate this with conditioned suppression of freezing behavior. However, levels of darting in this study were too low to make any definitive conclusions. In summary, females showed a significantly different behavioral profile than males in a task that tested the ability to discriminate among fear, safety and reward cues. This paradigm offers a great opportunity to test for mechanisms that are generating these behavioral sex differences in learned safety and reward seeking.
Adrenaline (Ad) and glucose released into the bloodstream during stress may strengthen contextual fear memory. However, no previous studies have detached the effects of glucose from Ad in this ...paradigm. Using Ad-deficient mice, we aimed to evaluate the effect of glucose on contextual fear memory when endogenous Ad is absent. Fear conditioning was performed in wild-type (WT) and Ad-deficient mice (129 × 1/SvJ) administered with glucose (30 or 10 mg/kg; i.p.) or/and Ad (0.01 mg/kg; i.p.) or vehicle (0.9% NaCl; i.p.). Catecholamines were quantified using HPLC-ED. Real-time qPCR was used to assess mRNA expression of hippocampal genes. WT and Ad-deficient mice display increased contextual fear memory when administered with glucose both in acquisition and context days when compared to vehicle. Also,
Nr4a3
and
Bdnf
mRNA expression increased in glucose-administered Ad-deficient mice. Sub-effective doses of glucose plus Ad administered simultaneously to Ad-deficient mice increased contextual fear memory, contrary to independent sub-effective doses. Concluding, glucose may be an important part of the peripheral to central pathway involved in the retrieval and reconsolidation of fear contextual memories independently of Ad, possibly due to increased hippocampal
Nr4a3
and
Bdnf
gene expression. Furthermore, Ad and glucose may act synergically to strengthen contextual fear memory.
Correctly assessing the total impact of predators on prey population growth rates (lambda, λ) is critical to comprehending the importance of predators in species conservation and wildlife management. ...Experiments over the past decade have demonstrated that the fear (antipredator responses) predators inspire can affect prey fecundity and early offspring survival in free-living wildlife, but recent reviews have highlighted the absence of evidence experimentally linking such effects to significant impacts on prey population growth. We experimentally manipulated fear in free-living wild songbird populations over three annual breeding seasons by intermittently broadcasting playbacks of either predator or nonpredator vocalizations and comprehensively quantified the effects on all the components of population growth, together with evidence of a transgenerational impact on offspring survival as adults. Fear itself significantly reduced the population growth rate (predator playback mean λ = 0.91, 95% CI = 0.80 to 1.04; nonpredator mean λ = 1.06, 95% CI = 0.96 to 1.16) by causing cumulative, compounding adverse effects on fecundity and every component of offspring survival, resulting in predator playback parents producing 53% fewer recruits to the adult breeding population. Fear itself was consequently projected to halve the population size in just 5 years, or just 4 years when the evidence of a transgenerational impact was additionally considered (λ = 0.85). Our results not only demonstrate that fear itself can significantly impact prey population growth rates in free-living wildlife, comparing them with those from hundreds of predator manipulation experiments indicates that fear may constitute a very considerable part of the total impact of predators.
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