Nervous System Control Research Articles

From 2D to 3D Co-Culture Systems: A Review of Co-Culture Models to Study the Neural Cells Interaction.

The central nervous system (CNS) controls and regulates the functional activities of the organ systems and maintains the unity between the body and the external environment. The advent of co-culture systems has made it possible to elucidate the interactions between neural cells in vitro and to reproduce complex neural circuits. Here, we classified the co-culture system as a two-dimensional (2D) co-culture system, a cell-based three-dimensional (3D) co-culture system, a tissue slice-based 3D co-culture system, an organoid-based 3D co-culture system, and a microfluidic platform-based 3D co-culture system. We provide an overview of these different co-culture models and their applications in the study of neural cell interaction. The application of co-culture systems in virus-infected CNS disease models is also discussed here. Finally, the direction of the co-culture system in future research is prospected.

Brain oscillatory activity in adolescent idiopathic scoliosis

Pathophysiology of Adolescent Idiopathic Scoliosis (AIS) is not yet completely understood. This exploratory study aims to investigate two aspects neglected in clinical practice: a defective postural central nervous system control in AIS, and alterations of body schema due to scoliosis spinal deformities. We recorded EEG data and balance data in four different standing positions in 14 adolescents with AIS and in 14 controls. A re-adaptation of the Image Marking Procedure (IMP) assessed body schema alterations on the horizontal (Body Perception Indices (BPIs)) and vertical direction (interacromial and bisiliac axes inclinations). Our results revealed no differences in balance control between groups; higher EEG alpha relative power over sensorimotor areas ipsilateral to the side of the curve and a significant increase of theta relative power localized over the central areas in adolescents with AIS. The difference in BPI shoulder and BPI waist significantly differed between the two groups. The inclinations of the perceived interacromial axes in adolescents with AIS was opposite to the real inclination. Increased theta activity and alpha lateralization observed may be a compensatory strategy to overcome sensorimotor dysfunction mirrored by altered body schema. Scoliosis onset might be preceded by sensorimotor control impairments that last during curve progression.

Detecting task-relevant spatiotemporal modules and their relation to motor adaptation.

How does the central nervous system (CNS) control our bodies, including hundreds of degrees of freedom (DoFs)? A hypothesis to reduce the number of DoFs posits that the CNS controls groups of joints or muscles (i.e., modules) rather than each joint or muscle independently. Another hypothesis posits that the CNS primarily controls motion components relevant to task achievements (i.e., task-relevant components). Although the two hypotheses are examined intensively, the relationship between the two concepts remains unknown, e.g., unimportant modules may possess task-relevant information. Here, we propose a framework of task-relevant modules, i.e., modules relevant to task achievements, while combining the two concepts mentioned above in a data-driven manner. To examine the possible role of the task-relevant modules, we examined the modulation of the task-relevant modules in a motor adaptation paradigm in which trial-to-trial modifications of motor output are observable. The task-relevant modules, rather than conventional modules, showed adaptation-dependent modulations, indicating the relevance of task-relevant modules to trial-to-trial updates of motor output. Our method provides insight into motor control and adaptation via an integrated framework of modules and task-relevant components.

The Influence of Energy Drinks on Lower Limb Muscle Fatigue and Recovery in Healthy Young Adults

Many studies have researched the influences of energy drinks (Edrinks) on the central nervous system, balance, and neuromuscular control. Understanding the neuromuscular adaptations that occur after drinking Celsius Edrinks on muscle fatigue and balance can be helpful when advising the use of Edrinks during physical activity. This study aims to understand the impact Celsius Edrinks has on neuromuscular adaptations in lower limb musculature during muscle fatigue, and balance in young, healthy adults. Two males and eighteen females were recruited for this study. The tibialis anterior, gastrocnemius, and Gluteus Medius neuromuscular data were captured with surface EMG electrodes. The number of single-leg heel raises repetitions and time to fatigue were recorded. Subjects were asked to perform single-leg heel raises to fatigue and single-leg balance activities pre-energy drink consumption, and the same tasks were repeated on the opposite not tested limb (post Edrinks consumption) to equate data points. Neuromuscular timing data suggested modifications on leg musculature. Although not significant, the amount of single-leg heel raises performed pre, and post-drink intake increased post-energy drink consumption. We infer that the ingredients in Celsius energy drinks, including caffeine, Taurine, and Guarana, alter nerve conduction velocity in lower limb musculature during exercise and balance activities. Future studies should research the influence of Celsius energy drinks in different scenarios and populations.

Targeting APC-Host Microbe interactions 2Robust control of a neurotropic parasite through MHC I presentation by infected neurons

Control of Central Nervous System (CNS) pathogens by CD8 T cells is pivotal to avoid fatal neuroinflammation. Yet the modalities of MHC I presentation in the brain are poorly understood. We analyzed the antigen presentation mechanisms underlying CD8 T cell-mediated brain restriction of Toxoplasma gondii, a neurotropic parasite that can chronically reside as cysts in the CNS and cause deadly encephalitis. First we engineered transgenic parasites expressing a model antigen that allows the establishment of latent toxoplasmosis in C57BL/6 mice, a mouse model that normally develops encephalitis following T. gondii infection. We show that MHC I presentation of that model antigen suffices to prevent encephalitis, even when restricted to the rapidly dividing tachyzoite stage. We find that improper parasite control in the context of encephalitis correlates with suboptimal MHC I presentation of T. gondii antigens by primary neuronal cultures. Using a new model of conditional MHC I-deficient mice, we finally demonstrate that brain parasite control requires neuronal MHC I presentation. Thus, MHC I presentation by CNS neurons is a crucial checkpoint that determines the clinical outcome of a prevalent and persisting brain infection.

Rotavirus Downregulates Tyrosine Hydroxylase in the Noradrenergic Sympathetic Nervous System in Ileum, Early in Infection and Simultaneously with Increased Intestinal Transit and Altered Brain Activities.

ABSTRACTWhile rotavirus diarrhea has been considered to occur only due to intrinsic intestinal effects within the enteric nervous system, we provide evidence for central nervous system control underlying the clinical symptomology. Our data visualize infection by large-scale three-dimensional (3D) volumetric tissue imaging of a mouse model and demonstrate that rotavirus infection disrupts the homeostasis of the autonomous system by downregulating tyrosine hydroxylase in the noradrenergic sympathetic nervous system in ileum, concomitant with increased intestinal transit. Interestingly, the nervous response was found to occur before the onset of clinical symptoms. In adult infected animals, we found increased pS6 immunoreactivity in the area postrema of the brain stem and decreased phosphorylated STAT5-immunoreactive neurons in the bed nucleus of the stria terminalis, which has been associated with autonomic control, including stress response. Our observations contribute to knowledge of how rotavirus infection induces gut-nerve-brain interaction early in the disease.

Neuroendocrine microRNAs linked to energy homeostasis: future therapeutic potential.

The brain orchestrates whole-body metabolism through an intricate system involving interneuronal crosstalk and communication. Specifically, a key player in this complex circuitry is the hypothalamus that controls feeding behaviour, energy expenditure, body weight and metabolism, whereby hypothalamic neurons sense and respond to circulating hormones, nutrients, and chemicals. Dysregulation of these neurons contributes to the development of metabolic disorders, such as obesity and type 2 diabetes. The involvement of hypothalamic microRNAs, post-transcriptional regulators of gene expression, in the central regulation of energy homeostasis has become increasingly apparent, although not completely delineated. This review summarizes current evidence demonstrating the regulation of feeding-related neuropeptides by brain-derived microRNAs as well as the regulation of specific miRNAs by nutrients and other peripheral signals. Moreover, the involvement of microRNAs in the central nervous system control of insulin, leptin, and estrogen signal transduction is examined. Finally, the therapeutic and diagnostic potential of microRNAs for metabolic disorders will be discussed andthe regulation of brain-derived microRNAs by nutrients and other peripheral signals is considered. Demonstrating a critical role of microRNAs in hypothalamic regulation of energy homeostasis is an innovative route to uncover novel biomarkers and therapeutic candidates for metabolic disorders.

Unilateral Cervical Vagotomy Modulates Immune Cell Profiles and the Response to a Traumatic Brain Injury.

TBI induces splenic B and T cell expansion that contributes to neuroinflammation and neurodegeneration. The vagus nerve, the longest of the cranial nerves, is the predominant parasympathetic pathway allowing the central nervous system (CNS) control over peripheral organs, including regulation of inflammatory responses. One way this is accomplished is by vagus innervation of the celiac ganglion, from which the splenic nerve innervates the spleen. This splenic innervation enables modulation of the splenic immune response, including splenocyte selection, activation, and downstream signaling. Considering that the left and right vagus nerves have distinct courses, it is possible that they differentially influence the splenic immune response following a CNS injury. To test this possibility, immune cell subsets were profiled and quantified following either a left or a right unilateral vagotomy. Both unilateral vagotomies caused similar effects with respect to the percentage of B cells and in the decreased percentage of macrophages and T cells following vagotomy. We next tested the hypothesis that a left unilateral vagotomy would modulate the splenic immune response to a traumatic brain injury (TBI). Mice received a left cervical vagotomy or a sham vagotomy 3 days prior to a fluid percussion injury (FPI), a well-characterized mouse model of TBI that consistently elicits an immune and neuroimmune response. Flow cytometric analysis showed that vagotomy prior to FPI resulted in fewer CLIP+ B cells, and CD4+, CD25+, and CD8+ T cells. Vagotomy followed by FPI also resulted in an altered distribution of CD11bhigh and CD11blow macrophages. Thus, transduction of immune signals from the CNS to the periphery via the vagus nerve can be targeted to modulate the immune response following TBI.

Octopamine signaling via OctαR is essential for a well-orchestrated climbing performance of adult Drosophila melanogaster

The biogenic amine octopamine (OA) orchestrates many behavioural processes in insects. OA mediates its function by binding to OA receptors belonging to the G protein-coupled receptors superfamily. Despite the potential relevance of OA, our knowledge about the role of each octopaminergic receptor and how signalling through these receptors controls locomotion still limited. In this study, RNA interference (RNAi) was used to knockdown each OA receptor type in almost all Drosophila melanogaster tissues using a tubP-GAL4 driver to investigate the loss of which receptor affects the climbing ability of adult flies. The results demonstrated that although all octopaminergic receptors are involved in normal negative geotaxis but OctαR-deficient flies had impaired climbing ability more than those deficient in other OA receptors. Mutation in OA receptors coding genes develop weak climbing behaviour. Directing knockdown of octαR either in muscular system or nervous system or when more specifically restricted to motor and gravity sensing neurons result in similar impaired climbing phenotype, indicating that within Drosophila legs, OA through OctαR orchestrated the nervous system control and muscular tissue responses. OctαR-deficient adult males showed morphometric changes in the length and width of leg parts. Leg parts morphometric changes were also observed in Drosophila mutant in OctαR. Transmission electron microscopy revealed that the leg muscles OctαR-deficient flies have severe ultrastructural changes compared to those of control flies indicating the role played by OctαR signalling in normal muscular system development. The severe impairment in the climbing performance of OctαR-deficient flies correlates well with the completely distorted leg muscle ultrastructure in these flies. Taken together, we could conclude that OA via OctαR plays an important multifactorial role in controlling locomotor activity of Drosophila.

Targeting CNS Neural Mechanisms of Gait in Stroke Neurorehabilitation.

The central nervous system (CNS) control of human gait is complex, including descending cortical control, affective ascending neural pathways, interhemispheric communication, whole brain networks of functional connectivity, and neural interactions between the brain and spinal cord. Many important studies were conducted in the past, which administered gait training using externally targeted methods such as treadmill, weight support, over-ground gait coordination training, functional electrical stimulation, bracing, and walking aids. Though the phenomenon of CNS activity-dependent plasticity has served as a basis for more recently developed gait training methods, neurorehabilitation gait training has yet to be precisely focused and quantified according to the CNS source of gait control. Therefore, we offer the following hypotheses to the field: Hypothesis 1. Gait neurorehabilitation after stroke will move forward in important ways if research studies include brain structural and functional characteristics as measures of response to treatment. Hypothesis 2. Individuals with persistent gait dyscoordination after stroke will achieve greater recovery in response to interventions that incorporate the current and emerging knowledge of CNS function by directly engaging CNS plasticity and pairing it with peripherally directed, plasticity-based motor learning interventions. These hypotheses are justified by the increase in the study of neural control of motor function, with emerging research beginning to elucidate neural factors that drive recovery. Some are developing new measures of brain function. A number of groups have developed and are sharing sophisticated, curated databases containing brain images and brain signal data, as well as other types of measures and signal processing methods for data analysis. It will be to the great advantage of stroke survivors if the results of the current state-of-the-art and emerging neural function research can be applied to the development of new gait training interventions.

When the levee of sympathetic outflow breaks

In this issue of Immunity, Bi etal. identify a microglia-neuron signaling axis that is critical for maintaining central control of the sympathetic nervous system. They find that platelet growth factor B released by microglia acts on neurons via PDGFRα to regulate sympathetic outflow. Disrupting this pathway leads to neuronal excitability, highlighting a promising therapeutic target to modulate sympathetic outflow and reduce hypertension.

Descending control of nociception in insects?

Modulation of nociception allows animals to optimize chances of survival by adapting their behaviour in different contexts. In mammals, this is executed by neurons from the brain and is referred to as the descending control of nociception. Whether insects have such control, or the neural circuits allowing it, has rarely been explored. Based on behavioural, neuroscientific and molecular evidence, we argue that insects probably have descending controls for nociception. Behavioural work shows that insects can modulate nocifensive behaviour. Such modulation is at least in part controlled by the central nervous system since the information mediating such prioritization is processed by the brain. Central nervous system control of nociception is further supported by neuroanatomical and neurobiological evidence showing that the insect brain can facilitate or suppress nocifensive behaviour, and by molecular studies revealing pathways involved in the inhibition of nocifensive behaviour both peripherally and centrally. Insects lack the endogenous opioid peptides and their receptors that contribute to mammalian descending nociception controls, so we discuss likely alternative molecular mechanisms for the insect descending nociception controls. We discuss what the existence of descending control of nociception in insects may reveal about pain perception in insects and finally consider the ethical implications of these novel findings.

Sex differences in autonomic responses to stress: implications for cardiometabolic physiology.

Chronic stress is a significant risk factor for negative health outcomes. Furthermore, imbalance of autonomic nervous system control leads to dysregulation of physiological responses to stress and contributes to the pathogenesis of cardiometabolic and psychiatric disorders. However, research on autonomic stress responses has historically focused on males, despite evidence that females are disproportionality affected by stress-related disorders. Accordingly, this mini-review focuses on the influence of biological sex on autonomic responses to stress in humans and rodent models. The reviewed literature points to sex differences in the consequences of chronic stress, including cardiovascular and metabolic disease. We also explore basic rodent studies of sex-specific autonomic responses to stress with a focus on sex hormones and hypothalamic-pituitary-adrenal axis regulation of cardiovascular and metabolic physiology. Ultimately, emerging evidence of sex differences in autonomic-endocrine integration highlights the importance of sex-specific studies to understand and treat cardiometabolic dysfunction.

A hypothesis about acupuncture's anxiolytic mechanism of action and its effect on the formation of self-efficacy beliefs and academic performance

Pre-exam anxiety is highly prevalent among students of all educational levels, leading to decreased performance. This anxiety causes psychological and physiological changes related to stress, which can affect the formation of self-efficacy beliefs. Studies have shown a correlation between pre-exam anxiety, self-efficacy and academic performance. Acupuncture (AC) has an anxiolytic effect recognized in the treatment of generalized anxiety disorder and anxiety in the pre-operative and pre-exam period. Stress-related variables such as cortisol level, blood pressure and heart rate can be modulated by AC. Brain regions related to the control of the autonomic nervous system, emotional, memory and cognitive processing are also modulated by AC. Therefore, the aim of this study is present a hypothesis about how the AC reduces anxiety and stress through neuroendocrine modulation, optimizing the formation of self-efficacy beliefs, which promote behaviors responsible for improved performance.

Eastern equine encephalitis virus rapidly infects and disseminates in the brain and spinal cord of cynomolgus macaques following aerosol challenge.

Eastern equine encephalitis virus (EEEV) is mosquito-borne virus that produces fatal encephalitis in humans. We recently conducted a first of its kind study to investigate EEEV clinical disease course following aerosol challenge in a cynomolgus macaque model utilizing the state-of-the-art telemetry to measure critical physiological parameters. Here, we report the results of a comprehensive pathology study of NHP tissues collected at euthanasia to gain insights into EEEV pathogenesis. Viral RNA and proteins as well as microscopic lesions were absent in the visceral organs. In contrast, viral RNA and proteins were readily detected throughout the brain including autonomic nervous system (ANS) control centers and spinal cord. However, despite presence of viral RNA and proteins, majority of the brain and spinal cord tissues exhibited minimal or no microscopic lesions. The virus tropism was restricted primarily to neurons, and virus particles (~61-68 nm) were present within axons of neurons and throughout the extracellular spaces. However, active virus replication was absent or minimal in majority of the brain and was limited to regions proximal to the olfactory tract. These data suggest that EEEV initially replicates in/near the olfactory bulb following aerosol challenge and is rapidly transported to distal regions of the brain by exploiting the neuronal axonal transport system to facilitate neuron-to-neuron spread. Once within the brain, the virus gains access to the ANS control centers likely leading to disruption and/or dysregulation of critical physiological parameters to produce severe disease. Moreover, the absence of microscopic lesions strongly suggests that the underlying mechanism of EEEV pathogenesis is due to neuronal dysfunction rather than neuronal death. This study is the first comprehensive investigation into EEEV pathology in a NHP model and will provide significant insights into the evaluation of countermeasure.

Involvement of the Dorsal Vagal Complex in Alcohol-Related Behaviors

The neurobiological mechanisms that regulate the development and maintenance of alcohol use disorder (AUD) are complex and involve a wide variety of within and between systems neuroadaptations. While classic reward, preoccupation, and withdrawal neurocircuits have been heavily studied in terms of AUD, viable treatment targets from this established literature have not proven clinically effective as of yet. Therefore, examination of additional neurocircuitries not classically studied in the context of AUD may provide novel therapeutic targets. Recent studies demonstrate that various neuropeptides systems are important modulators of alcohol reward, seeking, and intake behaviors. This includes neurocircuitry within the dorsal vagal complex (DVC), which is involved in the control of the autonomic nervous system, control of intake of natural rewards like food, and acts as a relay of interoceptive sensory information via interactions of numerous gut-brain peptides and neurotransmitter systems with DVC projections to central and peripheral targets. DVC neuron subtypes produce a variety of neuropeptides and transmitters and project to target brain regions critical for reward such as the mesolimbic dopamine system as well as other limbic areas important for the negative reinforcing and aversive properties of alcohol withdrawal such as the extended amygdala. This suggests the DVC may play a role in the modulation of various aspects of AUD. This review summarizes the current literature on neurotransmitters and neuropeptides systems in the DVC (e.g., norepinephrine, glucagon-like peptide 1, neurotensin, cholecystokinin, thyrotropin-releasing hormone), and their potential relevance to alcohol-related behaviors in humans and rodent models for AUD research. A better understanding of the role of the DVC in modulating alcohol related behaviors may lead to the elucidation of novel therapeutic targets for drug development in AUD.

Gut Microbiota Regulates the Sympathetic Nerve Activity and Peripheral Serotonin Through Hypothalamic MicroRNA-204 in Order to Increase the Browning of White Adipose Tissue in Obesity.

The prevalence of obesity is increasing worldwide, and novel therapeutic strategies such as enhancement of thermogenic pathways in white adipose tissue (WAT) are gaining more attention. The gut/brain axis plays an essential role in promoting the browning of WAT. However, the mechanism by which this axis regulates WAT function is not fully understood. On the other hand, the role of microRNAs (miRNAs) in the control of WAT browning has already been established. Therefore, understanding the communication pathways linking the gut/brain axis and miRNAs might establish a promising intervention for obesity.Our published data showed that microRNA-204 (miR-204), a microRNA that plays an important role in the control of the central nervous system (CNS) and the pathogenesis of obesity, is affected by gut dysbiosis. Therefore, miR-204 could be a key element that controls the browning of WAT by acting as a potential link between the gut microbiota and the brain. In this review, we summarized the current knowledge about communication pathways between the brain, gut, and miR-204 and examined the literature to discuss potential research directions that might lead to a better understanding of the mechanisms underlying the browning of WAT in obesity.

How Does the Central Nervous System Control Forthcoming Movement with Different Emotional Stimuli?

Maintaining postural balance is a key factor in human motor skills, based in part on emotional stimuli. Our objective in this study was to measure the effect of emotion on postural control as influenced by the direction of forthcoming movement. Eighteen right-handed women initiated a step forward or backward or remained in a static position after visualizing an emotional stimulus (positive, negative, or neutral). Center of pressure (COP) parameters (2D velocity, Medio-lateral (ML), and antero-posterior (AP) amplitude) were recorded for 3-second windows for movement direction and emotional stimulus. We observed a motion * direction effect on 2D velocity, characterized by a decrease in the emotional stimulus and static direction windows. The participants' ML amplitude was influenced by direction, and their reduced amplitude was evident in the presence of emotions. AP amplitude was high in the direction versus emotion window. In the static position, the AP amplitude was high in the direction window and low in the emotion window. The participants' movement planning and programming phase (direction window) was characterized by less oscillation for forward or backward movements and more oscillation before movement, suggesting anticipatory postural adjustments in the emotion window. Static direction was characterized by low oscillation, compared to forward and backward movement and in negative versus positive emotional context, proving the interactive impact of direction and emotion on COP amplitudes. Thus, postural control was influenced by both movement (direction) and emotional content (valence). This study provided insight regarding the interactive effect of emotion and direction on planning and programming forthcoming movement.

Comparative and Evolutionary Aspects of the Digestive System and Its Enteric Nervous System Control.

All life forms must gain nutrients from the environment and from single cell organisms to mammals a digestive system is present. Components of the digestive system that are recognized in mammals can be seen in the sea squirt that has had its current form for around 500my. Nevertheless, in mammals, the organ system that is most varied is the digestive system, its architecture being related to the dietary niche of each species. Forms include those of foregut or hindgut fermenters, single or multicompartment stomachs and short or capacious large intestines. Dietary niches include nectarivores, folivores, carnivores, etc. The human is exceptional in that, through food preparation (>80% of human consumption is prepared food in modern societies), humans can utilize a wider range of foods than other species. They are cucinivores, food preparers. In direct descendants of simple organisms, such as sponges, there is no ENS, but as the digestive tract becomes more complex, it requires integrated control of the movement and assimilation of its content. This is achieved by the nervous system, notably the enteric nervous system (ENS) and an array of gut hormones. An ENS is first observed in the phylum cnidaria, exemplified by hydra. But hydra has no collections of neurons that could in any way be regarded as a central nervous system. All animals more complex than hydra have an ENS, but not all have a CNS. In mammals, the ENS is extensive and is necessary for control of movement, enteric secretions and local blood flow, and regulation of the gut immune system. In animals with a CNS, the ENS and CNS have reciprocal connections. From hydra to human, an ENS is essential to life.

Influence of Spontaneous and Mechanical Ventilation on Frequency-Based Measures of Heart Rate Variability.

Frequency-based measures of heart rate variability have been shown to be a useful physiological marker in both clinical and research settings providing insight into the functioning of the autonomic nervous system. Ongoing interactions between the autonomic nervous system control of the heart and lung occurs during each ventilation cycle because of their anatomical position within the closed thoracic cavity. Mechanical ventilation and subsequent removal change the normal ventilator mechanics producing alterations in the tidal volume, intrathoracic pressure, and oxygen delivery. A noninvasive method called heart rate variability (HRV) can be used to evaluate this interaction during ventilation and can be quantified by applying frequency-based measures of the variability between heartbeats. Although HRV is a reliable method to measure alteration of the autonomic nervous system (ANS) function and cardiopulmonary interaction, there have been limited reports concerning the changes in the frequency-based measure of HRV during both spontaneous and mechanical ventilation. The purpose of this methodological study is therefore to describe the physiological influence of both spontaneous and mechanical ventilation on frequency-based measures of HRV.