Stressor controllability modulates the stress response in fish

Background In humans the stress response is known to be modulated to a great extent by psychological factors, particularly by the predictability and the perceived control that the subject has of the stressor. This psychological dimension of the stress response has also been demonstrated in animals phylogenetically closer to humans (i.e. mammals). However, its occurrence in fish, which represent a divergent vertebrate evolutionary lineage from that of mammals, has not been established yet, and, if present, would indicate a deep evolutionary origin of these mechanisms across vertebrates. Moreover, the fact that psychological modulation of stress is implemented in mammals by a brain cortical top-down inhibitory control over subcortical stress-responsive structures, and the absence of a brain cortex in fish, has been used as an argument against the possibility of psychological stress in fish, with implications for the assessment of fish sentience and welfare. Here, we have investigated the occurrence of psychological stress in fish by assessing how stressor controllability modulates the stress response in European seabass (Dicentrarchus labrax). Results Fish were exposed to either a controllable or an uncontrollable stressor (i.e. possibility or impossibility to escape a signaled stressor). The effect of loss of control (possibility to escape followed by impossibility to escape) was also assessed. Both behavioral and circulating cortisol data indicates that the perception of control reduces the response to the stressor, when compared to the uncontrollable situation. Losing control had the most detrimental effect. The brain activity of the teleost homologues to the sensory cortex (Dld) and hippocampus (Dlv) parallels the uncontrolled and loss of control stressors, respectively, whereas the activity of the lateral septum (Vv) homologue responds in different ways depending on the gene marker of brain activity used. Conclusions These results suggest the psychological modulation of the stress response to be evolutionary conserved across vertebrates, despite being implemented by different brain circuits in mammals (pre-frontal cortex) and fish (Dld-Dlv).

Ethology, Neurophysiology, Neuropharmacology, Sex Differences, and Effects of Stress on the Defensive Burying Paradigm: A Review

The defensive burying paradigm can inform how stressor controllability affects stress adaptation, which has clinical implications with regards to adaptive coping responses following presentation with a stressful situation. Active coping (notably defensive burying) is associated with a controllable stressor, promoting stress adaptation, thus decreases stress hormone levels. In opposition, chronic stress and uncontrollable stressors lead to an increase in passive coping behaviours, with elevated stress hormone levels. Several brain regions have been implicated in active and passive coping, as well as neurotransmitter systems, which can be evaluated via pharmacological manipulation. No sex differences were found in defensive burying, although there were effects of sex hormones within sex.

Ventral tegmental area glutamate neurons mediate the nonassociative consequences of traumatic stress

Exposure to trauma is a risk factor for the development of a number of mood disorders, and may enhance vulnerability to future adverse life events. Recent data implicate ventral tegmental area (VTA) glutamate neuronal activity as functionally important for signaling aversive or threating stimuli. However, it is unknown whether VTA glutamate neurons regulate transsituational outcomes that result from stress and whether these neurons are sensitive to stressor controllability. This work established an operant mouse paradigm to examine the impact of stressor controllability on VTA glutamate neuron function and stressor outcome. Uncontrollable (inescapable) stress, but not physically identical controllable (escapable) stress, produced social avoidance in male mice. Cell-type-specific calcium recordings showed that both controllable and uncontrollable stressors increased VTA glutamate neuronal activity. Chemogenetic reduction of VTA glutamate neuron activity prevented the behavioral sequelae of uncontrollable stress. Our results provide causal evidence that mice can be used to model stressor controllability and that VTA glutamate neurons may contribute to transsituational stressor outcomes, such as social avoidance and exaggerated fear that are observed within trauma-related disorders.

Don't Stress, It's Under Control: Neural Correlates of Stressor Controllability in Humans

Animal research has repeatedly shown that experience of control over an aversive event can protect against the negative consequences of later uncontrollable stress. Neurobiologically, this effect is assumed to correspond to persistent changes in the pathway linking the ventromedial prefrontal cortex (vmPFC) and the dorsal raphe nucleus. However, it remains unclear to what extent these findings translate to humans. During functional magnetic resonance imaging, we subjected participants to controllable and uncontrollable aversive but non-painful electric stimuli, as well as to a control condition without aversive stimulation. In each trial, a symbol signalled whether participants could terminate the stressor through correct performance in a button-matching task or whether the stressor would be randomly terminated, i.e., uncontrollable. Along with neural responses, we assessed participants' accuracy, reaction times, and heart rate. To relate neural activations and subjective experience, we asked participants to rate perceived control, helplessness, and stress. Results were largely in line with our hypotheses. The vmPFC was generally deactivated by stress, but this effect was attenuated when participants could terminate the stressor compared to when their responses had no effect. Furthermore, activation in stress-responsive regions, including the bilateral insula, was reduced during controllable trials. Under uncontrollable stress, greater vmPFC recruitment was linked to reduced feelings of helplessness. An investigation of condition-dependent differences in vmPFC connectivity yielded no significant results. Our findings further corroborate animal research and emphasise the role of the vmPFC in controllability-dependent regulation of stress responses. Based on the results, we discuss future directions in the context of resilience research and mental health promotion.

A Translational Paradigm to Study the Effects of Uncontrollable Stress in Humans

Theories on the aetiology of depression in humans are intimately linked to animal research on stressor controllability effects. However, explicit translations of established animal designs are lacking. In two consecutive studies, we developed a translational paradigm to study stressor controllability effects in humans. In the first study, we compared three groups of participants, one exposed to escapable stress, one yoked inescapable stress group, and a control group not exposed to stress. Although group differences indicated successful stress induction, the manipulation failed to differentiate groups according to controllability. In the second study, we employed an improved paradigm and contrasted only an escapable stress group to a yoked inescapable stress group. The final design successfully induced differential effects on self-reported perceived control, exhaustion, helplessness, and behavioural indices of adaptation to stress. The latter were examined in a new escape behaviour test which was modelled after the classic shuttle box animal paradigm. Contrary to the learned helplessness literature, exposure to uncontrollable stress led to more activity and exploration; however, these behaviours were ultimately not adaptive. We discuss the results and possible applications in light of the findings on learning and agency beliefs, inter-individual differences, and interventions aimed at improving resilience to stress-induced mental dysfunction.

A Distinctive Pattern of Hippocampal-Prefrontal Cortical Network Activity during Stress Predicts Learned Resistance

The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (mPFC) and the hippocampus are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded CA1 and mPFC neural activities in rats during the exposure to controllable, uncontrollable, or no shocks, and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from non-stressed animals and predict resistant or helpless individuals based on neural oscillatory dynamics. We identified a pattern of enhanced CA1-mPFC theta power, synchrony, cross-frequency interaction, and neuronal coupling that strongly predicted learned resistance, and that was lacking in helpless individuals. Our findings suggest that hippocampal-prefrontal network theta activity supports cognitive mechanisms of stress coping, and its impairment may underlie vulnerability to stress-related disorders.

Coping Models of Stress and Resilience

This chapter provides a review of research on the role of processes of coping as a source of resilience to the adverse effects of stress in childhood, adolescence, and adulthood. Advances in research on models of coping that distinguish responses based on stressor controllability are emphasized. Important similarities between models of coping and emotion regulation are highlighted to encourage integration of research on these two topics. Findings from research on the association between coping and symptoms of psychopathology in adulthood, childhood, and adolescence are reviewed. Directions for future research, including the implications of research on coping for the development of preventive interventions and treatments, are highlighted.