Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning.
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ABSTRACT:
SUBMITTER: Baker MR
PROVIDER: S-EPMC8187387 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Animals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individual's survival. As part of an animal's stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a natural olfactory alarm cue. Our results show that both proactive and reactive zebrafish learn and remember this fearful association. However, we note significant interaction effects between stress coping style and cognition. Zebrafish with the reactive stress coping style acquired the fear memory at a significantly faster rate than proactive fish. While both stress coping styles showed equal memory recall one day post-conditioning, reactive zebrafish showed significantly stronger recall of the conditioned context relative to proactive fish four days post-conditioning. Through understanding how stress coping strategies promote biases in processing salient information, we gain insight into mechanisms that can constrain adaptive behavioral responses.
| S-EPMC6617452 | biostudies-literature
Project description:Survival relies on optimizing behavioral responses through experience. Animals often react to acute stress by switching to passive behavioral responses when coping with environmental challenge. Despite recent advances in dissecting mammalian circuitry for Pavlovian fear, the neuronal basis underlying this form of non-Pavlovian anxiety-related behavioral plasticity remains poorly understood. Here, we report that aversive experience recruits the posterior paraventricular thalamus (PVT) and corticotropin-releasing hormone (CRH) and sensitizes a Pavlovian fear circuit to promote passive responding. Site-specific lesions and optogenetic manipulations reveal that PVT-to-central amygdala (CE) projections activate anxiogenic neuronal populations in the CE that release local CRH in response to acute stress. CRH potentiates basolateral (BLA)-CE connectivity and antagonizes inhibitory gating of CE output, a mechanism linked to Pavlovian fear, to facilitate the switch from active to passive behavior. Thus, PVT-amygdala fear circuitry uses inhibitory gating in the CE as a shared dynamic motif, but relies on different cellular mechanisms (postsynaptic long-term potentiation vs. presynaptic facilitation), to multiplex active/passive response bias in Pavlovian and non-Pavlovian behavioral plasticity. These results establish a framework promoting stress-induced passive responding, which might contribute to passive emotional coping seen in human fear- and anxiety-related disorders.
| S-EPMC6169733 | biostudies-literature
Project description:Both prenatal stress (PNS) exposure and a passive stress-coping style have been identified as risk factors for insulin resistance in rats. In the current study, we test the hypothesis that PNS and stress-coping style may interact in predicting susceptibility for metabolic disease. To test this hypothesis, adult male control and PNS offspring were behaviorally characterized using a defensive burying test to have either a passive or proactive stress-coping style. In adulthood, all rats were fed either a standard chow or a high-fat diet for 3 weeks. After 3 weeks of diet exposure, glucose and insulin levels were assessed during an oral glucose tolerance test. Under high-fat diet conditions, PNS rats display elevated glucose and insulin responses to the oral glucose tolerance test, indicative of glucose intolerance. Interestingly, these effects of PNS were far more pronounced in rats characterized by a passive stress-coping style. Additionally, the passively coping PNS rats also gained more weight on the high-fat diet than all other rats tested. This observation suggests that a stressful prenatal environment in combination with a passive stress-coping strategy may prime an individual to be sensitive to diet-induced obesity and type 2 diabetes.
| S-EPMC3959611 | biostudies-literature
Project description:Fear of physical activity (PA) is discussed as a barrier to regular exercise in patients with heart failure (HF), but HF-specific theoretical concepts are lacking. This study examined associations of fear of PA, heart-focused anxiety and trait anxiety with clinical characteristics and self-reported PA in outpatients with chronic HF. It was also investigated whether personality-related coping styles for dealing with health threats impact fear of PA via symptom perception. This cross-sectional study enrolled 185 HF outpatients from five hospitals (mean age 62 ± 11 years, mean ejection fraction 36.0 ± 12%, 24% women). Avoidance of PA, sports/exercise participation (yes/no) and the psychological characteristics were assessed by self-reports. Fear of PA was assessed by the Fear of Activity in Situations-Heart Failure (FActS-HF15) questionnaire. In multivariable regression analyses higher NYHA class (b = 0.26, p = 0.036) and a higher number of HF drugs including antidepressants (b = 0.25, p = 0.017) were independently associated with higher fear of PA, but not with heart-focused fear and trait anxiety. Of the three anxiety scores only increased fear of PA was independently associated with more avoidance behavior regarding PA (b = 0.45, SE = 0.06, p < 0.001) and with increased odds of no sports/exercise participation (OR = 1.34, 95% CI 1.03-1.74, p = 0.028). Attention towards cardiac symptoms and symptom distress were positively associated with fear of PA (p < 0.001), which explained higher fear of PA in patients with a vigilant (directing attention towards health threats) coping style (p = 0.004). Fear of PA assessed by the FActS-HF15 is a specific type of anxiety in patients with HF. Attention towards and being distressed by HF symptoms appear to play a central role in fear of PA, particularly in vigilant patients who are used to direct their attention towards health threats. These findings provide approaches for tailored interventions to reduce fear of PA and to increase PA in patients with HF. ClinicalTrials.gov ID: NCT02898246.
| S-EPMC11376548 | biostudies-literature
Project description:Within populations, individuals can vary in stress response, a multivariate phenomenon comprising neuroendocrine, physiological and behavioural traits.Verbal models of individual stress "coping style" have proposed that the behavioural component of this variation can be described as a single axis, with each individual's coping style being consistent across time and stress contexts.Focusing on this behavioural component of stress response and combining repeated measures of multiple traits with a novel multivariate modelling framework, we test for the existence of coping style variation and assess its stability across contexts in the Trinidadian guppy (Poecilia reticulata).Specifically, we test the following hypotheses: (1) there exists repeatable among-individual behavioural (co)variation ("personality") within a mild stress context consistent with a risk-averse-risk-prone continuum of behavioural coping style, (2) there is population-level plasticity in behaviour as a function of stressor severity, (3) there is among-individual variation in plasticity (i.e. IxE), and (4) the presence of IxE reduces cross-context stability of behavioural coping style.We found significant repeatable among-individual behavioural (co)variation in the mild stress context (open field trial), represented as an I matrix. However, I was not readily described by a simple risk-averse-risk-prone continuum as posited by the original coping style model. We also found strong evidence for population-level changes in mean behaviour with increasing stressor severity (simulated avian and piscine predation risks).Single-trait analyses did show the presence of individual-by-environment interactions (IxE), as among-individual cross-context correlations were significantly less than +1. However, multitrait analysis revealed the consequences of this plasticity variation were minimal. Specifically, we found little evidence for changes in the structure of I between mild and moderate stress contexts overall, and only minor changes between the two moderate contexts (avian vs. piscine predator).We show that a multivariate approach to assessing changes in among-individual (co)variance across contexts can prevent the over-interpretation of statistically significant, but small, individual-by-environment effects. While behavioural flexibility enables populations (and individuals) to respond rapidly to changes in the environment, multivariate personality structure can be conserved strongly across such contexts. A plain language summary is available for this article.
| S-EPMC5836853 | biostudies-literature
Project description:Cognitive dysfunction occurs in many debilitating conditions including Alzheimer's disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying potassium ion (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity.We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory.Constitutive Girk2-/- mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in gamma-aminobutyric acid neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal gamma-aminobutyric acid neurons but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/cornu ammonis 1 synapse in the dorsal hippocampus.Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders.
| S-EPMC4862939 | biostudies-literature
Project description:Background and purposeWomen are overrepresented in post-traumatic stress disorder (PTSD), a mental disorder characterised by ineffective inhibition of fear. The use of male animals dominates preclinical studies, which may contribute to a lack of understanding as to why this disparity exists. Thus, the current study explores sex differences in three mouse models of fear inhibition.Experimental approachAll experiments tested male and female C57Bl/6J mice. Experiment 1 employed two fear conditioning protocols, in which tones were paired with footshocks of differing intensity (moderate or intense). Fear recall and extinction were tested subsequently. In Experiment 2, safety learning was investigated. Tones were explicitly unpaired with footshocks during safety conditioning. Recall of safety learning was tested 24 hr later. Experiment 3 assessed a model of fear-safety discrimination. Cued stimuli were paired or never paired with footshocks during fear and safety conditioning, respectively. Discrimination between stimuli was assessed 24 hr later.Key resultsIn fear extinction, males, compared to females, responded with greater fear in sessions most proximal to conditioning but subsequently showed a more rapid fear extinction over time. Sex differences were not observed during safety learning. During fear-safety discrimination, both males and females discriminated between stimuli; however, males revealed a greater level of freezing to stimuli.Conclusion and implicationsThe current study provides evidence that sex differences influence fear but not safety-based behaviour in C57Bl/6J mice. These findings indicate that processing of fear, but not safety, may play a greater role in sex differences observed for PTSD.Linked articlesThis article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.
| S-EPMC6877798 | biostudies-literature
Project description:Animals experience stress in a variety of contexts and the behavioural and neuroendocrine responses to stress can vary among conspecifics. The responses across stressors often covary within an individual and are consistently different between individuals, which represent distinct stress coping styles (e.g. proactive and reactive). While studies have identified differences in peak glucocorticoid levels, less is known about how cortisol levels differ between stress coping styles at other time points of the glucocorticoid stress response. Here we quantified whole-body cortisol levels and stress-related behaviours (e.g. depth preference, movement) at time points representing the rise and recovery periods of the stress response in zebrafish lines selectively bred to display the proactive and reactive coping style. We found that cortisol levels and stress behaviours are significantly different between the lines, sexes and time points. Further, individuals from the reactive line showed significantly higher cortisol levels during the rising phase of the stress response compared with those from the proactive line. We also observed a significant correlation between individual variation of cortisol levels and depth preference but only in the reactive line. Our results show that differences in cortisol levels between the alternative stress coping styles extend to the rising phase of the endocrine stress response and that cortisol levels may explain variation in depth preferences in the reactive line. Differences in the timing and duration of cortisol levels may influence immediate behavioural displays and longer lasting neuromolecular mechanisms that modulate future responses.
| S-EPMC6549991 | biostudies-literature
Project description:Our objective was to characterize individual differences in fear conditioning and extinction in an outbred rat strain, to test behavioral predictors of these individual differences, and to assess their heritability. We fear-conditioned 100 Long-Evans rats, attempted to extinguish fear the next day, and tested extinction recall on the third day. The distribution of freezing scores after fear conditioning was skewed, with most rats showing substantial freezing; after fear extinction, the distribution was bimodal with most rats showing minimal freezing, but a substantial portion showing maximal freezing. Longer rearing episodes measured prior to conditioning predicted less freezing at the beginning of extinction, but differences in extinction learning were not predicted by any baseline exploratory behaviors. We tested the heritability of extinction differences by breeding rats from the top and bottom 20% of freezing scores during extinction recall. We then ran the offspring through the same conditioning/extinction procedure, with the addition of recording ultrasonic vocalizations throughout training and testing. Only a minority of rats emitted distress vocalizations during fear acquisition, but the incidence was less frequent in the offspring of good extinguishers than in poor extinguishers or randomly bred controls. The occurrence of distress vocalizations during acquisition predicted higher levels of freezing during fear recall regardless of breeding line, but the relationship between vocalization and freezing was no longer evident following extinction training, at which point freezing levels were influenced only by breeding and not by vocalization. The heritability (h(2)) of extinction recall was estimated at 0.36, consistent with human estimates.
| S-EPMC4138434 | biostudies-literature
Project description:Stress coping has been defined as the cognitive and behavioral efforts made to conquer, endure, or decrease external and internal demands and the conflicts between them. It has two main elements: the control or modification of the person-environment relationship causing the stress (i.e., problem-focused coping) and/or regulation of stressful feelings (i.e., emotion-focused coping). Research suggests that the expressions of brain-derived neurotrophic factor (BDNF) and neurotrophic tyrosine kinase receptor type 2 (NTRK2) play important roles in brain adaptation to investigate stress. To clarify the genetic basis of stress coping, we investigated the association of stress-coping strategies and social adaptation with single-nucleotide polymorphisms (SNPs) involved in neural plasticity, anxiety, and depression.In 252 healthy controls (94 women; 158 men), we measured and estimated the stress-coping style using the Lazarus-type stress-coping inventory, ego aptitude scale (EAS), and social adaptation self-evaluation scale (SASS). We investigated one SNP of BDNF (rs6265, Val/Met) and five SNPs of NTRK2 (rs11140800, rs1187286, rs1867283, rs1147198, and rs10868235).We observed significant associations between BDNF and emotion-focused strategies, seeking social support, self-control, and distancing. We also found significant associations between NTRK2 and cognitive strategies, problem-solving, confrontive- coping, seeking social support, distancing and positive reappraisal. Significant associations were also found between BDNF and critical attitudes and between NTRK2 and all seven ego-related factors on the EAS. In the SASS, the minor allele rs1867283 of NTRK2 had a significantly higher score than the heterozygote.These findings may provide insights into the partial effects of genetic mutations in BDNF and NTRK2 on stress tolerance and personality.
| S-EPMC4589807 | biostudies-literature