General Neuroscience

Neural Basis of Positive Behavior: Resilience

Esthefani Chávez Hinostroza


Introduction

Every human being in the course of his life goes through various situations before which he must give an answer in order to maintain his personal stability. This response can be both positive and negative, which will determine the impact that he will have as a functioning member of society, since he will be able to make the choice of behaving assertively or reticently. Given this scenario, this article will explore the neural basis of one of the positive behaviors that deserves to be promoted in individuals: resilience. The science of resilience will be discussed by focusing on the impact that genetics has on resilience, analyzing the neural circuits that influence stress coping, how the process of neurogenesis affects resilience, and finally, the neurobiology of the animal models with respect to resilience.

 

Genetics in resilience

    The heritability index is an essential element to determine the level of adaptability of an individual in highly stressful situations, which added to their personal history of response to these stressors will define the degree to which they will be able to be or not be resilient.

    The hypothalamic-pituitary-adrenal (HPA) axis is one of the components affected by genetics, since the functional variants of the mineralocorticoid receptor and glucocorticoid receptor (GC) genes are involved in establishing the threshold of the HPA axis and regulating its termination in response to stress [1].

    In addition, another study reported a link between the genetic variation FKBP5 and the inadequate recovery of HPA axis activity when performing the Trier test in healthy people, demonstrating a risk factor for high cortisol levels and psychopathology with respect to stress [2].

    Carriers of the short 5-HTTLPR allele show high rates of risk of depression due to exposure to stressful life events [3]. People with the Met158 allele have higher levels of dopamine and norepinephrine, which is why they are likely to manifest a greater degree of anxiety and derogatory behavior [4].

    At the same time, there are random epigenetic changes that facilitate resilience favoring survival in the face of highly complex events, while those changes related to vulnerability allow for better conduct in more satisfactory periods. The transcriptional mechanisms of resilience show that resilience is mediated by a unique series of changes that allow adaptation, but not the lack of maladaptive changes that occur in vulnerable individuals [5].

 

Neural circuits in stress coping

    Understanding the neural circuits that are responsible for resilience begins with fully comprehending the neural circuits responsible for fear, reward, and regulation of emotion. These circuits show how the brain handles unfamiliar situations.

    Recent studies show that the conditioning of fear is located in the amygdala, the extinction of fear memory involves the vmPFC, and the fear response that arises in the beginning and the subsequent flexible displacement is related to the activation of a network that gathers the striatum and the vmPFC [5, 6].

    The regulation of the emotions of conditioned fear could arise through connections with mechanisms of greater simplicity of extinction of fear [7]. The amygdala intervenes in the capacity of the stimuli produced by exposure to fear and the hippocampus acts on the contextual and temporal factors given by the conditioning of fear.

    Evidence has been found that interindividual variability in neuronal responses serves as a reward for anticipation in healthy individuals is linked to the Val158met COMT polymorphism [8]. Likewise, the optimism of traits regarding resilience may be associated with reward mechanisms. VTA dopamine neurons are activated in response to a reward and are blocked by hostile stimuli [9]. Certain neurons manage to be activated by the absence of expected reward, which is inferred that they are involved in the control of mood [10]. Some investigations refer to the intervention of the VTA-nucleus accumbens circuit in depressive behavior, but there is no consensus on the particular role of dopamine [5].

    The neural model of emotion regulation, in which the ventral and dorsal systems participate, is related to patterns of abnormal psychic disorders [11]. The amygdala, the hippocampus, subgenual ACC and PFC are involved in anxiety and mood disorders [12]. A cognitive re-evaluation, a mechanism for regulating emotions, when presented on a daily basis is linked to a higher CRP and, at the same time, less activation of the amygdala in the face of stressors; which suggests that through re-evaluation can be facilitated coping and reduce risks of depression and anxiety [13].

 

Figure 3. Neural circuitries of fear and reward

 

    A simple schematic of the key limbic regions in the fear and reward circuitries. These regions are highly interconnected and function as a series of integrated parallel circuits that regulate emotional states. Each is heavily innervated by the brain's monoaminergic systems —noradrenaline (from the locus coeruleus (LC)), dopamine (from the ventral tegmental área (VTA)) and serotonin (from the raphe nuclei (not shown)) — which are thought to modulate the activity of these areas. a | Fear-inducing sensory information is relayed through the thalamus (Thal) to the amygdala (Amy). The amygdala is particularly important for conditioned aspects of learning and memory, as is best studied in fear models. The hippocampus (HP) has a crucial role in declarative memory, but it probably functions more broadly in regulating emotional, including fear, and behaviour. b | The nucleus accumbens (NAc) is a key reward region that regulates an individual's responses to natural rewards and mediates the addicting actions of drugs of abuse. The prefrontal cortex (PFC) — which is composed of multiple regions (for example, the dorsolateral PFC, the medial PFC, the orbitofrontal cortex and the anterior cingulate cortex, among others) with distinct but overlapping functions — is sometimes also included in the limbic system and is essential to emotion regulation. PFC regions provide top down control of emotional responses by acting on both the amygdala and the NAc (a and b) [5].

 

Neurogenesis in the resilience process

    Neurogenesis of the hippocampus is a process influenced by physiological factors as inherent to the environment, whose role has been involved in the response to stress. Evidence has been found that neurogenesis allows greater coping with stress in animals with ablated neurogenesis. On the other hand, the lack of neurogenesis may not vary the ability to react to stress at the time of ablation, but may influence the response to future stressors. In addition, neurogenesis can be part of the resilient attitude in some animals evaluated in experiments, those with high basal neurogenesis or where this can be activated effectively; It should be mentioned that accurate coping allows neurogenesis and increases the possibility of a satisfactory subsequent coping [14].

 

Neurobiology of animal models of resilience

    Experimental studies have determined neural and molecular factors that facilitate susceptibility, which, if eliminated, contribute to stress resistance [15]. It should be noted that this approach proposes that resistance to stress is only a passive process, through which the absence of response from an animal is adaptive, but there is also evidence that active coping strategies influence it, being molecular as behavioral. [16]. In the course of stress resulting from social defeat, animals that take less docile postures during the attack show reduced social avoidance, revealing that this behavioral coping strategy can influence aggressive interaction and decrease the effects of stress [17]. This is related to a large number of unique variations in gene expression and chromatin changes in specific brain regions that are not seen in susceptible animals [18, 19].


References


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Esthefani Chávez Hinostroza

Esthefani Chávez Hinostroza


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