Lateralization of autonomic activity in response to limb-specific threat

In times of stress or danger, the autonomic nervous system (ANS) signals the fight or flight response. A canonical function of ANS activity is to globally mobilize metabolic resources, preparing the organism to respond to threat. Yet a body of research has demonstrated that, rather than displaying a homogenous pattern across the body, autonomic responses to arousing events - as measured through changes in electrodermal activity (EDA) - can differ between right and left body locations. Surprisingly, the metabolic function of such ANS asymmetry has not been investigated. In the current study, we investigated whether asymmetric autonomic responses could be induced through limb-specific aversive stimulation. Participants were given mild electric stimulation to either the left or right arm while EDA was monitored bilaterally. Across participants, a strong ipsilateral EDA response bias was observed, with increased EDA response in the hand adjacent to the stimulation. This effect was observable in over 50% of individual subjects. These results demonstrate that autonomic output is more complex than canonical interpretations suggest. We suggest that, in stressful situations, autonomic outputs can prepare either the whole-body fight or flight response, or a simply a limb-localized flick, which can effectively neutralize the threat while minimizing global resource consumption. These findings provide insight into the evolutionary pathway of neural systems processing general arousal by linking observed asymmetry in the peripheral arousal response to a historical leveraging of neural structures organized to mediate responses to localized threat.

Structures of PKA-phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy

Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure, yet the underlying molecular mechanism remains controversial. PLN interacts with sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent phosphorylation of PLN during the fight-or-flight response. Here, we present the crystal structures of the catalytic domain of PKA in complex with wild-type and DCM-mutant PLNs. Our structures, combined with the results from other biophysical and biochemical assays, reveal a common disease mechanism: the mutations in PLN reduce its phosphorylation level by changing its conformation and weakening its interactions with PKA. In addition, we demonstrate that another more ubiquitous SERCA-regulatory peptide, called another-regulin (ALN), shares a similar mechanism mediated by PKA in regulating SERCA activity.

Effect of Yoga Pranayama (Breathing Techniques) on the Vagus Nerve in Countering Major Depression and Related Ailments; A Literature Review

Major depressive disorder (MDD) is a major psychiatric condition associated with functional impairment and high levels of morbidity and mortality (M. Li, 2015) (Lohoff, 2010). It is characterized by mode alterations, diminished interests, impaired cognitive function and vegetative symptoms such as disturbed sleep and appetite changes (Christian Otte, 2016) are common patients suffering from MDD. Our nervous system is built around the balance and harmony of two opposing activities (Laurie Kelly McCorry, 2007). 1. The sympathetic nervous system (SNS) is associated with the fight or flight response. 2. The parasympathetic nervous system (PNS) is associated with relaxation, digestion, and regeneration. These two systems are meant to work in rhythmic alternation, a process that supports healthy rhythms of alertness and restfulness that facilitate physical and mental health (Shah, 2018). In order to treat ailments such as MDD, many techniques are used to stimulate the vagus nerve for better functioning (Bruno Bonaz, 2018). Different forms of pranayama tends to activate different branches of the autonomic nervous system, this causes positive changes to the oxygen consumption, metabolism and skin resistance. The literature evidence gathered states that the mechanisms of the vagul nerve stimulation helps in the parasympathetic activation in an event of stress depression and major depression. When the pranayam is mixed with certain yogic asana’s while controlling the breath, it seems to have a better countering of MDD and related disorders.

Effect of plant derived epinephrine on Saccharomyces cerevisiae

Epinephrine, a hormone known to produce ‘fight or flight’ response in higher animals, stimulates the hepatic cells to release stored glucose. The receptor for epinephrine is known to be a G-protein coupled receptor (GPCR). Baker’s yeast, also known as Saccharomyces cerevisiae, is reported to have a Gprotein coupled receptor (GPCR). The G-protein coupled receptor (GPCR) has a role in sensing glucose activation of adenylate cyclase during the switch from respirative/gluconeogenic metabolism to fermentation. Epinephrine, having varying roles in the animal system, has been reported in certain plant species. In the present study, Epinephrine quantified from extracts of G. globosa and P. oleracea was evaluated for its effect on the yeast cells.

Neurohumoral Cardiac Regulation: Optogenetics Gets Into the Groove

The cardiac autonomic nervous system (ANS) is the main modulator of heart function, adapting contraction force, and rate to the continuous variations of intrinsic and extrinsic environmental conditions. While the parasympathetic branch dominates during rest-and-digest sympathetic neuron (SN) activation ensures the rapid, efficient, and repeatable increase of heart performance, e.g., during the “fight-or-flight response.” Although the key role of the nervous system in cardiac homeostasis was evident to the eyes of physiologists and cardiologists, the degree of cardiac innervation, and the complexity of its circuits has remained underestimated for too long. In addition, the mechanisms allowing elevated efficiency and precision of neurogenic control of heart function have somehow lingered in the dark. This can be ascribed to the absence of methods adequate to study complex cardiac electric circuits in the unceasingly moving heart. An increasing number of studies adds to the scenario the evidence of an intracardiac neuron system, which, together with the autonomic components, define a little brain inside the heart, in fervent dialogue with the central nervous system (CNS). The advent of optogenetics, allowing control the activity of excitable cells with cell specificity, spatial selectivity, and temporal resolution, has allowed to shed light on basic neuro-cardiology. This review describes how optogenetics, which has extensively been used to interrogate the circuits of the CNS, has been applied to untangle the knots of heart innervation, unveiling the cellular mechanisms of neurogenic control of heart function, in physiology and pathology, as well as those participating to brain–heart communication, back and forth. We discuss existing literature, providing a comprehensive view of the advancement in the understanding of the mechanisms of neurogenic heart control. In addition, we weigh the limits and potential of optogenetics in basic and applied research in neuro-cardiology.

Authentic Fear Responses in Virtual Reality: A Mobile EEG Study on Affective, Behavioral and Electrophysiological Correlates of Fear

Fear is an evolutionary adaption to a hazardous environment, linked to numerous complex behavioral responses, e.g., the fight-or-flight response, suiting their respective environment. However, for the sake of experimental control, fear is mainly investigated under rather artificial laboratory conditions. The latter transform these evolutionary adaptions into artificial responses, like keystrokes. The immersive, multidimensional character of virtual reality (VR) enables realistic behavioral responses, overcoming aforementioned limitations. To investigate authentic fear responses from a holistic perspective, participants explored either a negative or a neutral VR cave. To promote real-life behavior, we built a physical replica of the cave, providing haptic sensations. Electrophysiological correlates of fear-related approach and avoidance tendencies, i.e., frontal alpha asymmetries (FAA) were evaluated. To our knowledge, this is the first study to simultaneously capture complex behavior and associated electrophysiological correlates under highly immersive conditions. Participants in the negative condition exhibited a broad spectrum of realistic fear behavior and reported intense negative affect as opposed to participants in the neutral condition. Despite these affective and behavioral differences, the groups could not be distinguished based on the FAAs for the greater part of the cave exploration. Taking the specific behavioral responses into account, the obtained FAAs could not be reconciled with well-known FAA models. Consequently, putting laboratory-based models to the test under realistic conditions shows that they may not unrestrictedly predict realistic behavior. As the VR environment facilitated non-mediated and realistic emotional and behavioral responses, our results demonstrate VR’s high potential to increase the ecological validity of scientific findings (video abstract: https://www.youtube.com/watch?v=qROsPOp87l4&feature=youtu.be).

Multiscale Modelling of β-Adrenergic Stimulation in Cardiac Electromechanical Function

β-adrenergic receptor stimulation (β-ARS) is a physiological mechanism that regulates cardiovascular function under stress conditions or physical exercise. Triggered during the so-called “fight-or-flight” response, the activation of the β-adrenergic receptors located on the cardiomyocyte membrane initiates a phosphorylation cascade of multiple ion channel targets that regulate both cellular excitability and recovery and of different proteins involved in intracellular calcium handling. As a result, β-ARS impacts both the electrophysiological and the mechanical response of the cardiomyocyte. β-ARS also plays a crucial role in several cardiac pathologies, greatly modifying cardiac output and potentially causing arrhythmogenic events. Mathematical patient-specific models are nowadays envisioned as an important tool for the personalised study of cardiac disease, the design of tailored treatments, or to inform risk assessment. Despite that, only a reduced number of computational studies of heart disease have incorporated β-ARS modelling. In this review, we describe the main existing multiscale frameworks to equip cellular models of cardiac electrophysiology with a β-ARS response. We also outline various applications of these multiscale frameworks in the study of cardiac pathology. We end with a discussion of the main current limitations and the future steps that need to be taken to adapt these models to a clinical environment and to incorporate them in organ-level simulations.

β-adrenergic stimulation synchronizes a broad spectrum of action potential firing rates of cardiac pacemaker cells towards a higher population average

The heartbeat is initiated by pacemaker cells residing in the sinoatrial node (SAN). SAN cells generate spontaneous action potentials (APs), i.e. normal automaticity. The sympathetic nervous system increases heart rate commensurate with blood supply and cardiac output demand, known as the fight-or-flight response, via stimulation of SAN β-adrenergic receptors (βAR). It is classically believed that all cells increase their spontaneous AP firing rate in a similar fashion. In the present study we measured βAR responses among 166 single SAN cells isolated from 33 guinea pig hearts. However, the responses substantially varied. In each cell changes in AP cycle length in response to βAR stimulation highly correlated (R2=0.97) with the AP cycle lengths before stimulation. While, as expected, on average the cells increased their pacemaker rate, greater responses were observed in cells with slower basal rates, and vice versa, cells with higher basal rates showed smaller responses, no responses, or even negative responses, i.e. their rate decreased. Thus, βAR stimulation synchronizes operation of the cell population towards a higher average rate, rather than uniformly shifting the rate in each cell, creating a new paradigm of fight-or-flight response among individual pacemaker SAN cells.

Understanding Emotions: Origins and Roles of the Amygdala

Emotions arise from activations of specialized neuronal populations in several parts of the cerebral cortex, notably the anterior cingulate, insula, ventromedial prefrontal, and subcortical structures, such as the amygdala, ventral striatum, putamen, caudate nucleus, and ventral tegmental area. Feelings are conscious, emotional experiences of these activations that contribute to neuronal networks mediating thoughts, language, and behavior, thus enhancing the ability to predict, learn, and reappraise stimuli and situations in the environment based on previous experiences. Contemporary theories of emotion converge around the key role of the amygdala as the central subcortical emotional brain structure that constantly evaluates and integrates a variety of sensory information from the surroundings and assigns them appropriate values of emotional dimensions, such as valence, intensity, and approachability. The amygdala participates in the regulation of autonomic and endocrine functions, decision-making and adaptations of instinctive and motivational behaviors to changes in the environment through implicit associative learning, changes in short- and long-term synaptic plasticity, and activation of the fight-or-flight response via efferent projections from its central nucleus to cortical and subcortical structures.

Children’s Peritraumatic Responses During Sexual Abuse Incidents: Exploring the Narratives of Children From Different Ethnoreligious Groups in Israel

The peritraumatic response of children during incidents of child sexual abuse (CSA) is a neglected construct in the literature. Despite the widespread use of the fight-flight-freeze model, recent studies have shown that in the unique context of child abuse, additional peritraumatic responses could be relevant. The current mixed-methods study examined children’s peritraumatic responses to CSA. The sample consisted of 249 forensic interviews with children aged from 4 to 13 years. An initial qualitative analysis resulted in identifying various ways in which the children responded to the abuse, the children’s decision-making around these responses, as well their perceptions of their response. This analysis was followed by quantitative analyses, which explored the frequency of these peritraumatic responses and their correlation with the characteristics of the children and abuse. Six peritraumatic response categories were identified, the most common being fight, flight, and fear. Only ethnoreligious identity was significantly correlated with the fight-or-flight response, with a significantly lower frequency among Muslim and ultra-Orthodox Jewish children. Frequency of abuse and perpetrator familiarity were correlated with the frequency of the fight-or-flight response, indicating that the latter was less relevant in reoccurring incidents of abuse and with perpetrators who were family members. The findings promote the conceptualization of children’s peritraumatic responses during incidents of abuse and the realization of the crucial role of children’s ecological systems in their peritraumatic responses to incidents of abuse.