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Sample records for vagal afferents stimulation

  1. Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: An electrophysiological study in healthy volunteers

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    Nonis, Romain; D’Ostilio, Kevin; Schoenen, Jean

    2017-01-01

    Background Benefits of cervical non-invasive vagus nerve stimulation (nVNS) devices have been shown in episodic cluster headache and preliminarily suggested in migraine, but direct evidence of vagus nerve activation using such devices is lacking. Vagal somatosensory evoked potentials (vSEPs) associated with vagal afferent activation have been reported for invasive vagus nerve stimulation (iVNS) and non-invasive auricular vagal stimulation. Here, we aimed to show and characterise vSEPs for cervical nVNS. Methods vSEPs were recorded for 12 healthy volunteers who received nVNS over the cervical vagus nerve, bipolar electrode/DS7A stimulation over the inner tragus, and nVNS over the sternocleidomastoid (SCM) muscle. We measured peak-to-peak amplitudes (P1-N1), wave latencies, and N1 area under the curve. Results P1-N1 vSEPs were observed for cervical nVNS (11/12) and auricular stimulation (9/12), with latencies similar to those described previously, whereas SCM stimulation revealed only a muscle artefact with a much longer latency. A dose-response analysis showed that cervical nVNS elicited a clear vSEP response in more than 80% of the participants using an intensity of 15 V. Conclusion Cervical nVNS can activate vagal afferent fibres, as evidenced by the recording of far-field vSEPs similar to those seen with iVNS and non-invasive auricular stimulation. PMID:28648089

  2. Plasticity of gastrointestinal vagal afferent satiety signals.

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    Page, A J; Kentish, S J

    2017-05-01

    The vagal link between the gastrointestinal tract and the central nervous system (CNS) has numerous vital functions for maintaining homeostasis. The regulation of energy balance is one which is attracting more and more attention due to the potential for exploiting peripheral hormonal targets as treatments for conditions such as obesity. While physiologically, this system is well tuned and demonstrated to be effective in the regulation of both local function and promoting/terminating food intake the neural connection represents a susceptible pathway for disruption in various disease states. Numerous studies have revealed that obesity in particularly is associated with an array of modifications in vagal afferent function from changes in expression of signaling molecules to altered activation mechanics. In general, these changes in vagal afferent function in obesity further promote food intake instead of the more desirable reduction in food intake. It is essential to gain a comprehensive understanding of the mechanisms responsible for these detrimental effects before we can establish more effective pharmacotherapies or lifestyle strategies for the treatment of obesity and the maintenance of weight loss. © 2016 John Wiley & Sons Ltd.

  3. Plasticity of gastro-intestinal vagal afferent endings.

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    Kentish, Stephen J; Page, Amanda J

    2014-09-01

    Vagal afferents are a vital link between the peripheral tissue and central nervous system (CNS). There is an abundance of vagal afferents present within the proximal gastrointestinal tract which are responsible for monitoring and controlling gastrointestinal function. Whilst essential for maintaining homeostasis there is a vast amount of literature emerging which describes remarkable plasticity of vagal afferents in response to endogenous as well as exogenous stimuli. This plasticity for the most part is vital in maintaining healthy processes; however, there are increased reports of vagal plasticity being disrupted in pathological states, such as obesity. Many of the disruptions, observed in obesity, have the potential to reduce vagal afferent satiety signalling which could ultimately perpetuate the obese state. Understanding how plasticity occurs within vagal afferents will open a whole new understanding of gut function as well as identify new treatment options for obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Cocaine- and amphetamine-regulated transcript mediates the actions of cholecystokinin on rat vagal afferent neurons.

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    De Lartigue, Guillaume; Dimaline, Rod; Varro, Andrea; Raybould, Helen; De la Serre, Claire Barbier; Dockray, Graham J

    2010-04-01

    Cholecystokinin (CCK) acts on vagal afferent neurons to inhibit food intake and gastric emptying; it also increases expression of the neuropeptide cocaine- and amphetamine-regulated transcript (CART), but the significance of this is unknown. We investigated the role of CARTp in vagal afferent neurons. Release of CART peptide (CARTp) from cultured vagal afferent neurons was determined by enzyme-linked immunosorbent assay. Expression of receptors and neuropeptides in rat vagal afferent neurons in response to CARTp was studied using immunohistochemistry and luciferase promoter reporter constructs. Effects of CARTp and CCK were studied on food intake. CCK stimulated CARTp release from cultured nodose neurons. CARTp replicated the effect of CCK in stimulating expression of Y2R and of CART itself in these neurons in vivo and in vitro, but not in inhibiting cannabinoid-1, melanin-concentrating hormone, and melanin-concentrating hormone-1 receptor expression. Effects of CCK on Y2R and CART expression were reduced by CART small interfering RNA or brefeldin A. Exposure of rats to CARTp increased the inhibitory action of CCK on food intake after short-, but not long-duration, fasting. The actions of CCK in stimulating CART and Y2R expression in vagal afferent neurons and in inhibiting food intake are augmented by CARTp; CARTp is released by CCK from these neurons, indicating that it acts as an autocrine excitatory mediator. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. NMDA receptors control vagal afferent excitability in the nucleus of the solitary tract.

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    Vance, Katie M; Rogers, Richard C; Hermann, Gerlinda E

    2015-01-21

    Previous behavioral studies have demonstrated that presynaptic N-methyl-d-aspartate (NMDA) receptors expressed on vagal afferent terminals are involved in food intake and satiety. Therefore, using in vitro live cell calcium imaging of prelabeled rat hindbrain slices, we characterized which NMDA receptor GluN2 subunits may regulate vagal afferent activity. The nonselective NMDA receptor antagonist d,l-2-amino-5-phosphonopentanoic acid (d,l-AP5) significantly inhibited vagal terminal calcium influx, while the excitatory amino acid reuptake inhibitor d,l-threo-β-benzyloxyaspartic acid (TBOA), significantly increased terminal calcium levels following pharmacological stimulation with ATP. Subunit-specific NMDA receptor antagonists and potentiators were used to identify which GluN2 subunits mediate the NMDA receptor response on the vagal afferent terminals. The GluN2B-selective antagonist, ifenprodil, selectively reduced vagal calcium influx with stimulation compared to the time control. The GluN2A-selective antagonist, 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl] benzyl]benzenesulfonamide (TCN 201) produced smaller but not statistically significant effects. Furthermore, the GluN2A/B-selective potentiator (pregnenolone sulfate) and the GluN2C/D-selective potentiator [(3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone; (CIQ)] enhanced vagal afferent calcium influx during stimulation. These data suggest that presynaptic NMDA receptors with GluN2B, GluN2C, and GluN2D subunits may predominantly control vagal afferent excitability in the nucleus of the solitary tract. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Plasticity of vagal afferent signaling in the gut

    Directory of Open Access Journals (Sweden)

    Gintautas Grabauskas

    2017-01-01

    Full Text Available Vagal sensory neurons mediate the vago-vagal reflex which, in turn, regulates a wide array of gastrointestinal functions including esophageal motility, gastric accommodation and pancreatic enzyme secretion. These neurons also transmit sensory information from the gut to the central nervous system, which then mediates the sensations of nausea, fullness and satiety. Recent research indicates that vagal afferent neurons process non-uniform properties and a significant degree of plasticity. These properties are important to ensure that vagally regulated gastrointestinal functions respond rapidly and appropriately to various intrinsic and extrinsic factors. Similar plastic changes in the vagus also occur in pathophysiological conditions, such as obesity and diabetes, resulting in abnormal gastrointestinal functions. A clear understanding of the mechanisms which mediate these events may provide novel therapeutic targets for the treatment of gastrointestinal disorders due to vago-vagal pathway malfunctions.

  7. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

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    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul

    2006-01-01

    Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are es...

  8. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin.

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    de Lartigue, Guillaume; de La Serre, Claire Barbier; Raybould, Helen E

    2011-11-30

    The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Genetic tracing of Nav1.8-expressing vagal afferents in the mouse.

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    Gautron, Laurent; Sakata, Ichiro; Udit, Swalpa; Zigman, Jeffrey M; Wood, John N; Elmquist, Joel K

    2011-10-15

    Nav1.8 is a tetrodotoxin-resistant sodium channel present in large subsets of peripheral sensory neurons, including both spinal and vagal afferents. In spinal afferents, Nav1.8 plays a key role in signaling different types of pain. Little is known, however, about the exact identity and role of Nav1.8-expressing vagal neurons. Here we generated mice with restricted expression of tdTomato fluorescent protein in all Nav1.8-expressing afferent neurons. As a result, intense fluorescence was visible in the cell bodies, central relays, and sensory endings of these neurons, revealing the full extent of their innervation sites in thoracic and abdominal viscera. For instance, vagal and spinal Nav1.8-expressing endings were seen clearly within the gastrointestinal mucosa and myenteric plexus, respectively. In the gastrointestinal muscle wall, labeled endings included a small subset of vagal tension receptors but not any stretch receptors. We also examined the detailed innervation of key metabolic tissues such as liver and pancreas and evaluated the anatomical relationship of Nav1.8-expressing vagal afferents with select enteroendocrine cells (i.e., ghrelin, glucagon, GLP-1). Specifically, our data revealed the presence of Nav1.8-expressing vagal afferents in several metabolic tissues and varying degrees of proximity between Nav1.8-expressing mucosal afferents and enteroendocrine cells, including apparent neuroendocrine apposition. In summary, this study demonstrates the power and versatility of the Cre-LoxP technology to trace identified visceral afferents, and our data suggest a previously unrecognized role for Nav1.8-expressing vagal neurons in gastrointestinal functions. Copyright © 2011 Wiley-Liss, Inc.

  10. Chronic kidney disease impairs renal nerve and haemodynamic reflex responses to vagal afferent input through a central mechanism.

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    Salman, Ibrahim M; Hildreth, Cara M; Phillips, Jacqueline K

    2017-05-01

    We investigated age- and sex-related changes in reflex renal sympathetic nerve activity (RSNA) and haemodynamic responses to vagal afferent stimulation in a rodent model of chronic kidney disease (CKD). Using anaesthetised juvenile (7-8weeks) and adult (12-13weeks) Lewis Polycystic Kidney (LPK) and Lewis control rats of either sex (n=63 total), reflex changes in RSNA, heart rate (HR) and mean arterial pressure (MAP) to vagal afferent stimulation (5-s train, 4.0V, 2.0-ms pulses, 1-16Hz) were measured. In all groups, stimulation of the vagal afferents below 16Hz produced frequency-dependent reductions in RSNA, HR and MAP, while a 16Hz stimulus produced an initial sympathoinhibition followed by sympathoexcitation. In juvenile LPK versus age-matched Lewis, sympathoinhibition was reduced when responses were expressed as % baseline (P<0.05), but not as microvolts, while bradycardic responses were greater. Reflex depressor responses were greater (P=0.015) only in juvenile female LPK. In adult LPK, reflex sympathoinhibition (%) was blunted (P<0.05), and an age-related decline apparent (when expressed as microvolts). Reflex reductions in HR and MAP were only diminished (P<0.05) in adult female LPK versus age-matched Lewis. Peak reflex sympathoexcitation at 16Hz did not differ between groups; however, area under the curve values were greater in the LPK versus Lewis (overall, 9±1 versus 19±3μVs, P<0.05) irrespective of age, suggestive of enhanced sympathoexcitatory drive in the LPK. Our data demonstrates a progressive deficit in the central processing of vagal afferent input and a differential sex influence on reflex regulation of autonomic function and blood pressure homeostasis in CKD. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  11. Effects of levodropropizine on vagal afferent C-fibres in the cat.

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    Shams, H; Daffonchio, L; Scheid, P

    1996-03-01

    1. Levodropropizine (LVDP) is an effective antitussive drug. Its effects on single-unit discharge of vagal afferent C-fibres were tested in anaesthetized cats to assess whether an inhibition of vagal C-fibres is involved in its antitussive properties. Vagal C-fibres, identified by their response to phenylbiguanide (PBG), were recorded via suction electrodes from the distal part of the cut vagus. Based on their response to lung inflation, C-fibres were classified as pulmonary (19 fibres) or non-pulmonary (6 fibres). 2. PBG increased the discharge rate of both C-fibre types and activated a respiratory reflex causing apnoea. This reflex was abolished when the second vagus nerve was cut as well, while PBG-mediated stimulation of the C-fibres was not affected by vagotomy. 3. LVDP was administered intravenously and the C-fibre response to PBG was compared with that before administration of the drug. LVDP reduced both the duration of apnoea and the response of the C-fibre to PBG. 4. Comparison of the C-fibre responses to PBG and to a mixture of PBG and LVDP revealed that the period of apnoea was shortened and the discharge rate of the C-fibre reduced when LVDP was present. 5. The LVDP-induced inhibition of the C-fibre response to PBG was on average 50% in pulmonary and 25% in non-pulmonary fibres. 6. These results suggest that LVDP significantly reduces the response of vagal C-fibres to chemical stimuli. It is, thus, likely that the antitussive effect of LVDP is mediated through its inhibitory action on C-fibres.

  12. Contribution of vagal afferents to respiratory reflexes evoked by acute inhalation of ozone in dogs

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    Schelegle, E.S.; Carl, M.L.; Coleridge, H.M.; Coleridge, J.C.; Green, J.F. (Univ. of California, Davis (United States))

    1993-05-01

    Acute inhalation of ozone induces vagally mediated rapid shallow breathing and bronchoconstriction. In spontaneously breathing anesthetized dogs, we attempted to determine whether afferent vagal C-fibers in the lower airways contributed to these responses. Dogs inhaled 3 ppm ozone for 40-70 min into the lower trachea while cervical vagal temperature was maintained successively at 37, 7, and 0 degrees C. At 37 degrees C, addition of ozone to the inspired air decreased tidal volume and dynamic lung compliance and increased breathing frequency, total lung resistance, and tracheal smooth muscle tension. Ozone still evoked significant effects when conduction in myelinated vagal axons was blocked selectively by cooling the nerves to 7 degrees C. Ozone-induced effects were largely abolished when nonmyelinated vagal axons were blocked by cooling to 0 degree C, breathing during ozone inhalation at 0 degree C being generally similar to that during air breathing at 0 degree C, except that minute volume and inspiratory flow were higher. We conclude that afferent vagal C-fibers in the lower airways make a major contribution to the acute respiratory effects of ozone and that nonvagal afferents contribute to the effects that survive vagal blockade.

  13. The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

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    Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe {sup i}n situ{sup .} The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs.

  14. Effects of levodropropizine on vagal afferent C-fibres in the cat.

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    Shams, H.; Daffonchio, L.; Scheid, P.

    1996-01-01

    1. Levodropropizine (LVDP) is an effective antitussive drug. Its effects on single-unit discharge of vagal afferent C-fibres were tested in anaesthetized cats to assess whether an inhibition of vagal C-fibres is involved in its antitussive properties. Vagal C-fibres, identified by their response to phenylbiguanide (PBG), were recorded via suction electrodes from the distal part of the cut vagus. Based on their response to lung inflation, C-fibres were classified as pulmonary (19 fibres) or no...

  15. Asystole Following Profound Vagal Stimulation During Hepatectomy

    Directory of Open Access Journals (Sweden)

    Preeta John

    2008-01-01

    Full Text Available Asystole in a non laparoscopic upper abdominal surgery following intense vagal stimulation is a rare event. This case report highlights the need for awareness of such a complication when a thoracic epidural anaesthetic has been given in addition to a general anaesthetic for an upper abdominal procedure. A combined thoracic epidural and general anaesthetic was given. The anterior abdominal wall was retracted forty minutes after administration of the epidural bolus. This maneuver resulted in a profound vagal response with bradycardia and asystole. The patient was resuscitated successfully with a cardiac massage, atropine and adrenaline and the surgery was resumed. Surgery lasted eleven hours and was uneventful.

  16. EGR1 Is a target for cooperative interactions between cholecystokinin and leptin, and inhibition by ghrelin, in vagal afferent neurons.

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    de Lartigue, Guillaume; Lur, Gyorgy; Dimaline, Rod; Varro, Andrea; Raybould, Helen; Dockray, Graham J

    2010-08-01

    Food intake is regulated by signals from peripheral organs, but the way these are integrated remains uncertain. Cholecystokinin (CCK) from the intestine and leptin from adipocytes interact to inhibit food intake. Our aim was to examine the hypothesis that these interactions occur at the level of vagal afferent neurons via control of the immediate early gene EGR1. We now report that CCK stimulates redistribution to the nucleus of early growth response factor-1 (EGR1) in these neurons in vivo and in culture, and these effects are not dependent on EGR1 synthesis. Leptin stimulates EGR1 expression; leptin alone does not stimulate nuclear translocation, but it strongly potentiates the action of CCK. Ghrelin inhibits CCK-stimulated nuclear translocation of EGR1 and leptin-stimulated EGR1 expression. Expression of the gene encoding the satiety peptide cocaine- and amphetamine-regulated transcript (CARTp) is stimulated by CCK via an EGR1-dependent mechanism, and this is strongly potentiated by leptin. Leptin potentiated inhibition of food intake by endogenous CCK in the rat in conditions reflecting changes in EGR1 activation. The data indicate that by separately regulating EGR1 activation and synthesis, CCK and leptin interact cooperatively to define the capacity for satiety signaling by vagal afferent neurons; manipulation of these interactions may be therapeutically beneficial.

  17. Chronic exposure to low dose bacterial lipopolysaccharide inhibits leptin signaling in vagal afferent neurons.

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    de La Serre, Claire B; de Lartigue, Guillaume; Raybould, Helen E

    2015-02-01

    Bacterially derived factors are implicated in the causation and persistence of obesity. Ingestion of a high fat diet in rodents and obesity in human subjects is associated with chronic elevation of low plasma levels of lipopolysaccharide (LPS), a breakdown product of Gram-negative bacteria. The terminals of vagal afferent neurons are positioned within the gut mucosa to convey information from the gut to the brain to regulate food intake and are responsive to LPS. We hypothesized that chronic elevation of LPS could alter vagal afferent signaling. We surgically implanted osmotic mini-pumps that delivered a constant, low-dose of LPS into the intraperitoneal cavity of rats (12.5 μg/kg/hr for 6 weeks). LPS-treated rats developed hyperphagia and showed marked changes in vagal afferent neuron function. Chronic LPS treatment reduced vagal afferent leptin signaling, characterized by a decrease in leptin-induced STAT3 phosphorylation. In addition, LPS treatment decreased cholecystokinin-induced satiety. There was no alteration in leptin signaling in the hypothalamus. These findings offer a mechanism by which a change in gut microflora can promote hyperphagia, possibly leading to obesity. Copyright © 2014. Published by Elsevier Inc.

  18. Age-related changes in vagal afferents innervating the gastrointestinal tract.

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    Phillips, Robert J; Walter, Gary C; Powley, Terry L

    2010-02-16

    Recent progress in understanding visceral afferents, some of it reviewed in the present issue, serves to underscore how little is known about the aging of the visceral afferents in the gastrointestinal (GI) tract. In spite of the clinical importance of the issue-with age, GI function often becomes severely compromised-only a few initial observations on age-related structural changes of visceral afferents are available. Primary afferent cell bodies in both the nodose ganglia and dorsal root ganglia lose Nissl material and accumulate lipofucsin, inclusions, aggregates, and tangles. Additionally, in changes that we focus on in the present review, vagal visceral afferent terminals in both the muscle wall and the mucosa of the GI tract exhibit age-related structural changes. In aged animals, both of the vagal terminal types examined, namely intraganglionic laminar endings and villus afferents, exhibit dystrophic or regressive morphological changes. These neuropathies are associated with age-related changes in the structural integrity of the target organs of the affected afferents, suggesting that local changes in trophic environment may give rise to the aging of GI innervation. Given the clinical relevance of GI tract aging, a more complete understanding both of how aging alters the innervation of the gut and of how such changes might be mitigated should be made research priorities. Copyright 2009 Elsevier B.V. All rights reserved.

  19. Chemical afferent vagal axotomy blocks re-intake after partial withdrawal of gastric food contents.

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    Zafra, María A; Molina, Filomena; Puerto, Amadeo

    2017-12-01

    The aim of this study was to investigate the biological process by which animals regulate meal size. An experimental procedure for its study is to examine food re-intake after partial withdrawal of gastric food contents. The aim of the present experiments was to investigate the role of vagal afferents in food re-intake after perivagal administration of capsaicin, a neurotoxin that specifically damages weakly myelinated or unmyelinated vagal sensory axons. In experiment 1, capsaicin-treated animals initially consumed higher amounts of food in comparison to controls (in first 24 hours) but their excess intake was compensated for in subsequent daily satiation tests. However, capsaicin treatment impaired the common short-term re-intake behavior observed in control rats after partial removal of gastric food nutrients, and the lesioned animals consumed significantly less food than had been withdrawn after completion of the initial meal; moreover, in this deficit condition, no counteraction was observed in subsequent repeated tests. This behavioral disturbance cannot be attributed to an indirect effect of capsaicin on gastric emptying volume, because the stomach contents were similar in both groups (Experiment 2). These findings are discussed in terms of the critical role played by vagal afferents in rapid visceral adjustments related to short-term food intake, as also observed in other gastrointestinal regulatory behaviors that require immediate processing of visceral sensory information.

  20. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons.

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    de Lartigue, Guillaume; Barbier de la Serre, Claire; Espero, Elvis; Lee, Jennifer; Raybould, Helen E

    2011-07-01

    Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.

  1. Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus.

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    Yu, Xiaoyun; Hu, Youtian; Yu, Shaoyong

    2014-08-15

    Acid reflux-induced heartburn and noncardiac chest pain are processed peripherally by sensory nerve endings in the wall of the esophagus, but the underlying mechanism is still unclear. This study aims to determine the effects of acid on esophageal vagal nociceptive afferent subtypes. Extracellular single-unit recordings were performed in guinea pig vagal nodose or jugular C fiber neurons by using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. We recorded action potentials (AP) of esophageal nodose or jugular C fibers evoked by acid perfusion and compared esophageal distension-evoked AP before and after acid perfusion. Acid perfusion for 30 min (pH range 7.4 to 5.8) did not evoke AP in nodose C fibers but significantly decreased their responses to esophageal distension, which could be recovered after washing out acid for 90 min. In jugular C fibers, acid perfusion not only evoked AP but also inhibited their responses to esophageal distension, which were not recovered after washing out acid for 120 min. Lower concentration of capsaicin perfusion mimicked acid-induced effects in nodose and jugular C fibers. Pretreatment with TRPV1 antagonist AMG9810, but not acid-sensing ion channel (ASIC) inhibitor amiloride, significantly inhibited acid-induced effects in nodose and jugular C fiber. These results demonstrate that esophageal vagal nociceptive afferent nerve subtypes display distinctive responses to acid. Acid activates jugular, but not nodose, C fibers and inhibits both of their responses to esophageal distension. These effects are mediated mainly through TRPV1. This inhibitory effect is a novel finding and may contribute to esophageal sensory/motor dysfunction in acid reflux diseases. Copyright © 2014 the American Physiological Society.

  2. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Jelsing, Jacob; van de Wall, Esther H E M

    2009-01-01

    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R...... blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac...... system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia....

  3. Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity.

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    de Lartigue, Guillaume; Ronveaux, Charlotte C; Raybould, Helen E

    2014-09-01

    The vagal afferent pathway senses hormones released from the gut in response to nutritional cues and relays these signals to the brain. We tested the hypothesis that leptin resistance in vagal afferent neurons (VAN) is responsible for the onset of hyperphagia by developing a novel conditional knockout mouse to delete leptin receptor selectively in sensory neurons (Nav1.8/LepR (fl/fl) mice). Chow fed Nav1.8/LepR (fl/fl) mice weighed significantly more and had increased adiposity compared with wildtype mice. Cumulative food intake, meal size, and meal duration in the dark phase were increased in Nav1.8/LepR (fl/fl) mice; energy expenditure was unaltered. Reduced satiation in Nav1.8/LepR (fl/fl) mice is in part due to reduced sensitivity of VAN to CCK and the subsequent loss of VAN plasticity. Crucially Nav1.8/LepR (l/fl) mice did not gain further weight in response to a high fat diet. We conclude that disruption of leptin signaling in VAN is sufficient and necessary to promote hyperphagia and obesity.

  4. TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.

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    Yu, Xiaoyun; Hu, Youtian; Ru, Fei; Kollarik, Marian; Undem, Bradley J; Yu, Shaoyong

    2015-03-15

    Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception. Copyright © 2015 the American Physiological Society.

  5. Effects of Electrical Vagal Stimulation and Bilateral Vagotomy on ...

    African Journals Online (AJOL)

    Effect of electrical vagal stimulation and bilateral vagotomy on the flow and electrolyte composition of bile was studied in fasted and anaesthetized male albino Wistar Rats. Entero-hepatic circulation was maintained artificially by continuous infusion of 1% sodium teurocholate. In each experiment, bile was collected at 15 ...

  6. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

    Science.gov (United States)

    Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

    2015-03-15

    Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. Copyright © 2015 the American Physiological Society.

  7. Pathology Influences Blood Pressure Change following Vagal Stimulation in an Animal Intubation Model.

    OpenAIRE

    Jones, P; Guillaud, L; Desbois, C; Benoist, J.F.; Combrisson, H; Dauger, S.; Peters, M J

    2013-01-01

    The haemodynamic response to critical care intubation is influenced by the use of sedation and relaxant drugs and the activation of the vagal reflex. It has been hypothesized that different disease states may have a contrasting effect on the cardiovascular response to vagal stimulation. Our objective was to determine whether the blood pressure response to vagal stimulation was modified by endotoxaemia or hypovolaemia.

  8. Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling and satiation in diet induced obese rats.

    Science.gov (United States)

    de Lartigue, Guillaume; Barbier de la Serre, Claire; Espero, Elvis; Lee, Jennifer; Raybould, Helen E

    2012-01-01

    The gastrointestinal hormone cholecystokinin (CCK) plays an important role in regulating meal size and duration by activating CCK1 receptors on vagal afferent neurons (VAN). Leptin enhances CCK signaling in VAN via an early growth response 1 (EGR1) dependent pathway thereby increasing their sensitivity to CCK. In response to a chronic ingestion of a high fat diet, VAN develop leptin resistance and the satiating effects of CCK are reduced. We tested the hypothesis that leptin resistance in VAN is responsible for reducing CCK signaling and satiation. Lean Zucker rats sensitive to leptin signaling, significantly reduced their food intake following administration of CCK8S (0.22 nmol/kg, i.p.), while obese Zucker rats, insensitive to leptin, did not. CCK signaling in VAN of obese Zucker rats was reduced, preventing CCK-induced up-regulation of Y2 receptor and down-regulation of melanin concentrating hormone 1 receptor (MCH1R) and cannabinoid receptor (CB1). In VAN from diet-induced obese (DIO) Sprague Dawley rats, previously shown to become leptin resistant, we demonstrated that the reduction in EGR1 expression resulted in decreased sensitivity of VAN to CCK and reduced CCK-induced inhibition of food intake. The lowered sensitivity of VAN to CCK in DIO rats resulted in a decrease in Y2 expression and increased CB1 and MCH1R expression. These effects coincided with the onset of hyperphagia in DIO rats. Leptin signaling in VAN is required for appropriate CCK signaling and satiation. In response to high fat feeding, the onset of leptin resistance reduces the sensitivity of VAN to CCK thus reducing the satiating effects of CCK.

  9. Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling and satiation in diet induced obese rats.

    Directory of Open Access Journals (Sweden)

    Guillaume de Lartigue

    Full Text Available The gastrointestinal hormone cholecystokinin (CCK plays an important role in regulating meal size and duration by activating CCK1 receptors on vagal afferent neurons (VAN. Leptin enhances CCK signaling in VAN via an early growth response 1 (EGR1 dependent pathway thereby increasing their sensitivity to CCK. In response to a chronic ingestion of a high fat diet, VAN develop leptin resistance and the satiating effects of CCK are reduced. We tested the hypothesis that leptin resistance in VAN is responsible for reducing CCK signaling and satiation.Lean Zucker rats sensitive to leptin signaling, significantly reduced their food intake following administration of CCK8S (0.22 nmol/kg, i.p., while obese Zucker rats, insensitive to leptin, did not. CCK signaling in VAN of obese Zucker rats was reduced, preventing CCK-induced up-regulation of Y2 receptor and down-regulation of melanin concentrating hormone 1 receptor (MCH1R and cannabinoid receptor (CB1. In VAN from diet-induced obese (DIO Sprague Dawley rats, previously shown to become leptin resistant, we demonstrated that the reduction in EGR1 expression resulted in decreased sensitivity of VAN to CCK and reduced CCK-induced inhibition of food intake. The lowered sensitivity of VAN to CCK in DIO rats resulted in a decrease in Y2 expression and increased CB1 and MCH1R expression. These effects coincided with the onset of hyperphagia in DIO rats.Leptin signaling in VAN is required for appropriate CCK signaling and satiation. In response to high fat feeding, the onset of leptin resistance reduces the sensitivity of VAN to CCK thus reducing the satiating effects of CCK.

  10. Selectivity for Specific Cardiovascular Effects of Vagal Nerve Stimulation With a Multi-Contact Electrode Cuff

    NARCIS (Netherlands)

    Ordelman, Simone Cornelia Maria Anna; Kornet, L.; Cornelussen, R.; Buschman, H.P.J.; Veltink, Petrus H.

    2012-01-01

    The cardiovascular system can be influenced by electrically stimulating the vagal nerve. Selectivity for specific cardiac fibers may be limited when stimulating at the cervical level. Our objective was to increase effectiveness and selectivity for cardiovascular effects of vagal nerve stimulation by

  11. Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability

    DEFF Research Database (Denmark)

    Landau, Anne M.; Dyve, Suzan; Jakobsen, Steen

    2015-01-01

    Background Vagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention. Objective/hypothesis We hypothesized that salutary effects of VNS are mediated, at least in part, by augmentation of the inhibitory effects of cortical...... binding potentials for selected brain regions of each animal. Results VNS treatment markedly reduced the binding potential of yohimbine in limbic, thalamic and cortical brain regions, in inverse correlation with the baseline binding potential. Conclusion The result is consistent with release...... of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS....

  12. Effects of auricular electrical stimulation on vagal activity in healthy men: evidence from a three-armed randomized trial.

    Science.gov (United States)

    La Marca, Roberto; Nedeljkovic, Marko; Yuan, Lizhuang; Maercker, Andreas; Elhert, Ulrike

    2010-04-01

    The activity of the VN (vagus nerve) is negatively associated with risk factors such as stress and smoking, morbidity and mortality. In contrast, it is also a target of therapeutic intervention. VN stimulation is used in depression and epilepsy. Because of its high invasivity and exclusive application to therapy-resistant patients, there is interest in less invasive methods affecting the VN. Several studies examining acupuncture report beneficial effects on vagal activity. However, findings are inconsistent, and applied methods are heterogeneous resulting in difficulties in interpretation. The purpose of the present study was evaluation of the effects of acupuncture on vagal activity in a three-armed randomized trial while controlling several disturbing factors. Fourteen healthy men participated in random order in four examinations: a control condition without intervention, a condition with placebo, manual acupuncture and electroacupuncture. Acupuncture was conducted on the concha of the ear, as there is neuroanatomical evidence for vagal afferents. Each examination took place once, with a week's time between examinations. RSA(TR) (respiratory sinus arrhythmia adjusted for tidal volume) indicating vagal activity was measured continuously. The study was conducted partially blind in accordance with recommendations. After controlling for respiration,condition-specific pain sensation, individual differences in belief of acupuncture effectiveness and time effects not attributable to the interventions, electroacupuncture but not manual acupuncture was found to have a positive effect on RSA(TR). The results underline the potential role of auricular electrical stimulation to induce an increase in vagal activity, and it therefore might be used as preventive or adjuvant therapeutic intervention promoting health.

  13. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Brock, C; Brock, B; Aziz, Q

    2016-01-01

    -VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which...

  14. Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a series of three cases.

    Science.gov (United States)

    Tomei, Krystal L; Mau, Christine Y; Ghali, Michael; Pak, Jayoung; Goldstein, Ira M

    2018-03-01

    We describe three children with Angelman syndrome and medically refractory epilepsy. Case series of three pediatric patients with Angelman syndrome and medically refractory epilepsy. All three patients failed medical treatment and were recommended for vagal nerve stimulator (VNS) implantation. Following VNS implantation, all three patients experienced reduction in seizure frequency greater than that afforded by medication alone. We present vagal nerve stimulator implantation as a viable treatment option for medically refractory epilepsy associated with Angelman syndrome.

  15. Intragastric gavage with denatonium benzoate acutely induces neuronal activation in the solitary tract nucleus via the vagal afferent pathway.

    Science.gov (United States)

    Jung, Hyo Young; Kim, Woosuk; Yoo, Dae Young; Nam, Sung Min; Kim, Jong Whi; Choi, Jung Hoon; Yoon, Yeo Sung; Kim, Hye Young; Hwang, In Koo

    2014-12-01

    Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.

  16. Pathology influences blood pressure change following vagal stimulation in an animal intubation model.

    Science.gov (United States)

    Jones, Peter; Guillaud, Laurent; Desbois, Christophe; Benoist, Jean-Francois; Combrisson, Helene; Dauger, Stephane; Peters, Mark J

    2013-01-01

    The haemodynamic response to critical care intubation is influenced by the use of sedation and relaxant drugs and the activation of the vagal reflex. It has been hypothesized that different disease states may have a contrasting effect on the cardiovascular response to vagal stimulation. Our objective was to determine whether the blood pressure response to vagal stimulation was modified by endotoxaemia or hypovolaemia. New Zealand White rabbits were anaesthetised with urethane before tracheotomy. The exposed left Vagus nerve of randomised groups of control (n = 11), endotoxin (n = 11, 1 mg/kg), hypovolaemia 40% (n = 8) and hypovolaemia 20% (n = 8) rabbits were subjected to 10 Hz pulsed electrical stimulations of 25 s duration every 15 min. Haemodynamic parameters were recorded from a catheter in the right carotid artery connected to an iWorx monitor. Serum catecholamines were measured every 30 min using reverse-phase ion-pairing liquid chromatography. The change in blood pressure after vagal stimulation was compared to controls for one hour after the first death in the experimental groups. 29% of the rabbits died in the hypovolaemia 40% group and 27% in the endotoxin group. One rabbit died in the hypovolaemia 40% group before vagal stimulation and was excluded. Following electrical stimulation of the Vagus nerve there was a fall in blood pressure in control rabbits. Blood pressure was conserved in the hypovolaemic rabbits compared to controls (pblood pressure to decrease more than the controls. Serum catecholamines were significantly raised in both the hypovolaemic and endotoxaemic rabbits. Pathology may contribute to modifications in blood pressure when vagal activation occurs. Patients who are either already vasoconstricted, or not vasoplegic, may be less at risk from intubation-related vagally mediated reductions in blood pressure than those with vasodilatory pathologies.

  17. Pathology influences blood pressure change following vagal stimulation in an animal intubation model.

    Directory of Open Access Journals (Sweden)

    Peter Jones

    Full Text Available PURPOSE: The haemodynamic response to critical care intubation is influenced by the use of sedation and relaxant drugs and the activation of the vagal reflex. It has been hypothesized that different disease states may have a contrasting effect on the cardiovascular response to vagal stimulation. Our objective was to determine whether the blood pressure response to vagal stimulation was modified by endotoxaemia or hypovolaemia. METHODS: New Zealand White rabbits were anaesthetised with urethane before tracheotomy. The exposed left Vagus nerve of randomised groups of control (n = 11, endotoxin (n = 11, 1 mg/kg, hypovolaemia 40% (n = 8 and hypovolaemia 20% (n = 8 rabbits were subjected to 10 Hz pulsed electrical stimulations of 25 s duration every 15 min. Haemodynamic parameters were recorded from a catheter in the right carotid artery connected to an iWorx monitor. Serum catecholamines were measured every 30 min using reverse-phase ion-pairing liquid chromatography. The change in blood pressure after vagal stimulation was compared to controls for one hour after the first death in the experimental groups. RESULTS: 29% of the rabbits died in the hypovolaemia 40% group and 27% in the endotoxin group. One rabbit died in the hypovolaemia 40% group before vagal stimulation and was excluded. Following electrical stimulation of the Vagus nerve there was a fall in blood pressure in control rabbits. Blood pressure was conserved in the hypovolaemic rabbits compared to controls (p<0.01. For the endotoxaemic rabbits, there was a non-significant trend for the mean blood pressure to decrease more than the controls. Serum catecholamines were significantly raised in both the hypovolaemic and endotoxaemic rabbits. CONCLUSIONS: Pathology may contribute to modifications in blood pressure when vagal activation occurs. Patients who are either already vasoconstricted, or not vasoplegic, may be less at risk from intubation-related vagally mediated

  18. Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus.

    Science.gov (United States)

    Lee, Jennifer; Cummings, Bethany P; Martin, Elizabeth; Sharp, James W; Graham, James L; Stanhope, Kimber L; Havel, Peter J; Raybould, Helen E

    2012-03-15

    Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon-like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide (GIP), which act to change gastrointestinal function and regulate postprandial plasma glucose. There is evidence that both release and action of incretin hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent neurons in response to intestinal glucose in a model of type 2 diabetes mellitus, the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3-mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle (water, 0.5 ml /100 g body wt) or glucose (330 μmol/100 g body wt); after 6 min tissue was removed and cellular activation was determined by immunohistochemistry for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats, pCaMKII immunoreactivity was increased in duodenal 5-HT (P < 0.001), K (P < 0.01) and L (P < 0.01) cells in response to glucose; glucose-induced activation of all three cell types was significantly reduced in RD and 3MD compared with PD rats. Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD compared with PD rats (P < 0.01). Administration of glucose significantly increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose-induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent neurons (P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest that glucose sensing in enteroendocrine and enterochromaffin cells and activation of neural pathways is markedly impaired in UCD-T2DM rats.

  19. Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

    Science.gov (United States)

    Ronveaux, Charlotte C; Tomé, Daniel; Raybould, Helen E

    2015-04-01

    Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal afferent neurons (VANs). The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments. © 2015 American Society for Nutrition.

  20. Relief of fecal incontinence by sacral nerve stimulation linked to focal brain activation

    DEFF Research Database (Denmark)

    Lundby, Lilli; Møller, Arne; Buntzen, Steen

    2011-01-01

    This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence.......This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence....

  1. Successful removal and reimplant of vagal nerve stimulator device after 10 years

    Directory of Open Access Journals (Sweden)

    Marco Giulioni

    2012-01-01

    Full Text Available The number of implanted vagal nerve stimulators is growing and the need for removal or revision of the devices will become even more frequent. A significant concern about Vagus Nerve Stimulation (VNS therapy is the presence of the spiral stimulating electrodes, wrapped around the nerve, once treatment is considered ineffective or is no longer desired. Our purpose is to demonstrate the feasibility of complete removal and replacement of the vagal nerve stimulator electrodes using microsurgical technique even after a long period, without damaging the nerve. We attempted removal and replacement of spiral stimulating electrodes from a patient who received a 10-year long VNS therapy for drug-resistant epilepsy. Our results indicate that the spiral electrodes may be safely removed from the vagus nerve, even after several years. The reversibility of lead implantation may enhance the attractiveness of VNS therapy. Furthermore, with a correct microsurgical technique, it is possible to respect the normal anatomy and functionality of vagal nerve and to reimplant a new VNS system with all its components, maintaining the same therapeutic efficacy after many years.

  2. Activation of cannabinoid CB1 receptors suppresses the ROS-induced hypersensitivity of rat vagal lung C-fiber afferents.

    Science.gov (United States)

    Yeh, Chou-Ming; Ruan, Ting; Lin, Yu-Jung; Hsu, Tien-Huan

    2016-10-01

    Reactive oxygen species (ROS), including H2O2, have been shown to induce hypersensitivity of vagal lung C-fibers (VLCFs) mainly through receptor potential ankyrin 1 (TRPA1) and P2X receptors. Cannabinoids (CBs) exert antinociceptive effects by binding to specific CB receptors, designated CB1 and CB2 (type 2) for type 1 and type 2, respectively. We investigated whether activation of CB receptors can suppress ROS-mediated VLCF hypersensitivity and, if so, what type(s) of CB receptors are involved. Aerosolized H2O2 (0.05%) was inhaled by anesthetized spontaneously breathing rats (n = 304) to sensitize VLCFs. Airway reflex reactivity to intravenous capsaicin, a VLCF stimulant, was measured. Perivagal pretreatments with various types of agonists and antagonists, a technique that can modulate VLCF sensitivity, were made to delineate the roles of the CB receptors. Aerosolized H2O2 induced an augmented apneic response to capsaicin, which was blocked by bilateral vagotomy or by perivagal capsaicin treatment, suggesting that the response is mediated through VLCFs. Perivagal treatment with HU210 (a nonselective CB agonist) or ACPA (a selective CB1 receptor agonist), but not JWH133 (a CB2 receptor agonist), attenuated this H2O2-induced VLCF hypersensitivity. The suppressive effects of HU210 and ACPA were prevented by an additional treatment with AM251 (a selective CB1 antagonist), but not with AM630 (a selective CB2 antagonist). Perivagal treatment with a combination of ACPA, HC030031 (a TRPA1 receptor antagonist), and iso-PPADS (a P2X receptor antagonist) further attenuated the H2O2-induced VLCF hypersensitivity, as compared with treatment with a combination of HC030031 and iso-PPADS. Our results suggest that activation of CB1 receptors may suppress the ROS-mediated VLCF hypersensitivity through a mechanism that is at least partly distinct from the function of TRPA1 and P2X receptors. Copyright © 2016. Published by Elsevier Ltd.

  3. Anorexia‐cachexia syndrome in hepatoma tumour‐bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC‐1/GDF15

    Science.gov (United States)

    Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N.; Langhans, Wolfgang; Lutz, Thomas A.; Blomqvist, Anders

    2016-01-01

    Abstract Background The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour‐derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour‐derived macrophage inhibitory cytokine‐1 (MIC‐1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC‐1 in mice. Methods Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC‐1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. Results In tumour‐bearing sham‐operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer‐induced anorexia or body weight loss. Tumour‐bearing rats had substantially increased MIC‐1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. Conclusions These findings demonstrate the importance of the AP in the mediation of cancer‐dependent anorexia and body weight loss and support a pathological role of MIC‐1 as a tumour‐derived factor mediating CACS, possibly via an AP

  4. Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

    OpenAIRE

    Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

    2010-01-01

    Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recordin...

  5. Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

    Science.gov (United States)

    Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

  6. Do the psychological effects of vagus nerve stimulation partially mediate vagal pain modulation?

    Science.gov (United States)

    Frangos, Eleni; Richards, Emily A; Bushnell, M Catherine

    2017-01-01

    There is preclinical and clinical evidence that vagus nerve stimulation modulates both pain and mood state. Mechanistic studies show brainstem circuitry involved in pain modulation by vagus nerve stimulation, but little is known about possible indirect descending effects of altered mood state on pain perception. This possibility is important, since previous studies have shown that mood state affects pain, particularly the affective dimension (pain unpleasantness). To date, human studies investigating the effects of vagus nerve stimulation on pain perception have not reliably measured psychological factors to determine their role in altered pain perception elicited by vagus nerve stimulation. Thus, it remains unclear how much of a role psychological factors play in vagal pain modulation. Here, we present a rationale for including psychological measures in future vagus nerve stimulation studies on pain.

  7. Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

    Science.gov (United States)

    Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

    2010-01-01

    Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recording responses from the pharyngeal, laryngeal, and hyoid muscles, esophagus, and the lower esophageal sphincter (LES). The effects on the medullary vagal nuclei of the stimuli: slow distension (N=10), rapid distension (N=9), and in control animals (N=10) were identified using the immunohistochemical analysis of c-fos. The experimental groups were stimulated 3 times per minute for 3 hours. After the experiment, the brains were removed and processed for c-fos immunoreactivity or thioinin. We found that slow balloon distension activated the esophago-UES contractile reflex and esophago LES relaxation response, and rapid air injection activated the belch and its component reflexes. Slow balloon distension activated the NTSce, NTSdl, NTSvl, DMNc, DMNr and NAr; and rapid air injection primarily activated AP, NTScd, NTSim, NTSis, NTSdm, NTSvl, NAc and NAr. We concluded that different sets of medullary vagal nuclei mediate different reflexes of the esophagus activated from different sets of mechanoreceptors. The NTScd is the primary NTS subnucleus mediating reflexes from the mucosal rapidly adapting touch receptors, and the NTSce is the primary NTS subnucleus mediating reflexes from the muscular slowly adapting tension receptors. The AP may be involved in mediation of belching. PMID:20971087

  8. Tactile stimulation with kinesiology tape alleviates muscle weakness attributable to attenuation of Ia afferents.

    Science.gov (United States)

    Konishi, Yu

    2013-01-01

    Prolonged vibration stimulation to normal individuals could lead to muscle weakness attributable to attenuation of afferent feedback. This weakness is neurophysiologically similar to that seen in patients with knee injury. Theoretically, increasing input to gamma motor neurons could reverse this weakness. Sensory input to these neurons from skin could indirectly increase Ia afferent feedback. The present study examined the effect of this tactile stimulation in the form of Kinesiology tape on muscle weakness attributable to attenuation of afferent feedback. Randomized, crossover design. All participants were measured their eccentric maximal voluntary contractions under the 2 conditions (taping and non-taping). First, maximal voluntary contraction during eccentric contraction was measured as baseline. For the taping condition, Kinesiology tape was applied around each subject's knee joint during maximal voluntary contraction measurement after vibration. For the non-taping condition, tape was not applied during maximal voluntary contraction measurement after vibration. Mean percentage changes between pre- and post-vibration stimulation were compared between two conditions. Maximal voluntary contraction and average electromyography of taping condition was significantly larger than that of non-taping condition. Our results suggest that tactile stimulation in the form of Kinesiology tape inhibits the decline of both strength and electromyography. Alpha motor neuron activity attenuated by prolonged vibration would thus be partially rescued by tactile stimulation. These results indirectly suggest that stimulation of skin around the knee could counter quadriceps femoris weakness due to attenuated Ia afferent activity. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  9. Haemodynamic Responses to Selective Vagal Nerve Stimulation under Enalapril Medication in Rats.

    Directory of Open Access Journals (Sweden)

    Mortimer Gierthmuehlen

    Full Text Available Selective vagal nerve stimulation (sVNS has been demonstrated to lower blood pressure (BP in rats without causing major side effects. This method might be adapted for the treatment of therapy-resistant hypertension in patients. Converting enzyme inhibitors (CEIs are among the first drugs that are administered for arterial hypertension and prominently reduce BP primarily by interacting with the renin-angiotensin system of the kidneys. Beyond the reduction of BP, CEI have a positive effect on the survival rate after myocardial infarction; they reduce the rates of stroke and improve the neurohormonal status in heart-failure patients. If sVNS might be introduced as a therapy against resistant hypertension, patients will at least partially stay on their CEI medication. It is therefore the aim of this study to investigate the influence of the CEI enalapril on the haemodynamic and respiratory effects of sVNS. In 10 male Wistar rats, a polyimide-based multichannel-cuff-electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibres. Stimulation parameters were adapted to the thresholds of the individual animals and included repetition frequencies between 30 and 50 Hz, amplitudes of 0.5 to 1.5 mA and pulse widths between 0.4 ms and 1.0 ms. BP responses were detected with a microtip transducer in the left carotid artery, and electrocardiography was recorded with subcutaneous electrodes. After intravenous administration of enalapril (2 mg/kg bodyweight, the animals' mean arterial blood pressures (MAPs decreased significantly, while the heart rates (HRs were not significantly influenced. The effects of sVNS on BP and HR were attenuated by enalapril but were still present. We conclude that sVNS can lower the MAP during enalapril treatment without relevant side effects.

  10. Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb.

    Science.gov (United States)

    Khan, Serajul I; Burne, John A

    2010-01-13

    Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI origin of cutaneous inhibition of the motoneurons.

  11. Semiconditional electrical stimulation of pudendal nerve afferents stimulation to manage neurogenic detrusor overactivity in patients with spinal cord injury.

    Science.gov (United States)

    Lee, Young-Hee; Kim, Jung Moon; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min

    2011-10-01

    To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Patients with neurogenic detrusor overactivity were subdivided into complete injury and incomplete injury groups by ASIA classification and subdivided into tetraplegia and paraplegia groups by neurologic level of injury. Bladder function, such as bladder volumes infused to the bladder until the first occurrence of neurogenic detrusor overactivity (V(ini)) and the last contraction suppressed by electrical stimulation (V(max)) was measured by water cystometry (CMG) and compared with the results of each subgroup. Among the 40 subjects, 35 patients showed neurogenic detrusor overactivity in the CMG study. Among these 35 patients, detrusor overactivity was suppressed effectively by pudendal nerve afferent electrical stimulation in 32 patients. The infusion volume until the occurrence of the first reflex contraction (V(ini)) was 99.4±80.3 ml. The volume of saline infused to the bladder until the last contraction suppressed by semiconditional pudendal nerve stimulation (V(max)) was 274.3±93.2 ml, which was significantly greater than V(ini). In patients with good response to the pudendal nerve afferent stimulation, the bladder volume significantly increased by stimulation in all the patients. In this study, semiconditional electrical stimulation on the dorsal penile afferent nerve could effectively inhibit neurogenic detrusor overactivity and increase bladder volume in patients with spinal cord injury.

  12. Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract.

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    Beaumont, Eric; Campbell, Regenia P; Andresen, Michael C; Scofield, Stephanie; Singh, Krishna; Libbus, Imad; KenKnight, Bruce H; Snyder, Logan; Cantrell, Nathan

    2017-08-01

    Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts.NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents but

  13. Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report.

    Science.gov (United States)

    Patwardhan, Ravish V; Dellabadia, John; Rashidi, Mahmoud; Grier, Laurie; Nanda, Anil

    2005-08-01

    To describe a case of left vagal nerve stimulation (VNS) resulting in immediate cessation of status epilepticus (SE) with good neurological outcome. A 30-year-old man with medically intractable seizures including episodes of SE was successfully treated using left VNS. After requiring discontinuation of phenytoin, valproic acid, carbamazepine, and topiramate because of severe allergic reactions resembling Stevens-Johnson syndrome, the patient required pentobarbital coma along with phenobarbital, tiagabine, and levetiracetam for seizure frequency reduction. He underwent left vagal nerve stimulator placement after nearly 9 days of barbiturate-induced coma, with stimulation initiated in the operating room. On the following day, electroencephalography revealed resolution of previously observed periodic lateral epileptiform discharges and the patient was free of seizures. Prestimulation seizure frequency was recorded at 59 times a day, with some seizures enduring 45 minutes despite barbiturate coma. Poststimulation, the patient has been free of seizures for 19 days and is presently taking only levetiracetam and phenobarbital, from which he continues to be successfully weaned without seizures. He is awake, alert, and can recall events leading up to his seizures, with good long-term memory and residual left upper extremity and lower extremity weakness. This case illustrates the role of left vagal stimulation in the treatment of SE and otherwise medically intractable seizures caused by allergic reactions. To our knowledge, this is the first case in the world literature for adults reporting cessation of SE after VNS. Another case with a similar improvement has been reported in the pediatric population.

  14. Semiconditional Electrical Stimulation of Pudendal Nerve Afferents Stimulation to Manage Neurogenic Detrusor Overactivity in Patients with Spinal Cord Injury

    OpenAIRE

    Lee, Young-Hee; Kim, Jung Moon; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min

    2011-01-01

    Objective To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Method Patients with neurogenic detrusor overactivity were subdivided into complete i...

  15. Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers.

    Science.gov (United States)

    Woock, John P; Yoo, Paul B; Grill, Warren M

    2010-05-25

    Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s) and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations. A finite element model (FEM) of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs) along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in alpha-chloralose anesthetized cats. Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration. A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.

  16. Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers

    Directory of Open Access Journals (Sweden)

    Grill Warren M

    2010-05-01

    Full Text Available Abstract Background Intraurethral electrical stimulation (IES of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations. Methods A finite element model (FEM of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in α-chloralose anesthetized cats. Results Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration. Conclusions A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.

  17. Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow.

    Science.gov (United States)

    Uitterdijk, André; Yetgin, Tuncay; te Lintel Hekkert, Maaike; Sneep, Stefan; Krabbendam-Peters, Ilona; van Beusekom, Heleen M M; Fischer, Trent M; Cornelussen, Richard N; Manintveld, Olivier C; Merkus, Daphne; Duncker, Dirk J

    2015-09-01

    Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction.

  18. Combined Vagal Stimulation and Limb Remote Ischemic Perconditioning Enhances Cardioprotection via an Anti-inflammatory Pathway.

    Science.gov (United States)

    Wang, Qiang; Liu, Gao-Pu; Xue, Fu-Shan; Wang, Shi-Yu; Cui, Xin-Long; Li, Rui-Ping; Yang, Gui-Zhen; Sun, Chao; Liao, Xu

    2015-10-01

    Various combined interventions to acquire enhanced cardioprotection are prevalent focuses of current research. This randomized experiment assessed whether combined vagal stimulation perconditioning (VSPerC) and limb remote ischemic perconditioning (LRIPerC) improved cardioprotection compared to the use of either treatment alone in an in vivo rat model of myocardial ischemia/reperfusion injury. A total of 100 male Sprague Dawley rats were randomly allocated into five groups: sham group, ischemia/reperfusion (IR) group, VSPerC group, LRIPerC group, and combined VSPerC and LRIPerC (COMPerC) group. Serum enzymatic markers, inflammatory cytokines, myocardial inflammatory cytokines, and infarct size were assessed. Infarct size decreased significantly in the COMPerC group compared to the VSPerC and LRIPerC groups. Serum intercellular adhesion molecule 1 (ICAM-1) level at 120 min of reperfusion, myocardial interleukin-1 (IL-1), ICAM-1, and tumor necrosis factor α (TNF-α) levels in the ischemic region decreased significantly in the COMPerC group compared to the VSPerC group, but myocardial IL-10 levels in the nonischemic region increased markedly in the COMPerC group. Serum TNF-α levels at 30, 60, and 120 min of reperfusion; serum IL-1, IL-6, ICAM-1, and high mobility group box-1 protein (HMGB-1) levels at 120 min of reperfusion; and myocardial IL-1, IL-6, ICAM-1, and TNF-α levels in the ischemic region decreased significantly in the COMPerC group compared to the LRIPerC group. However, myocardial IL-10 levels in both ischemic and nonischemic regions were evidently higher in the COMPerC group. This study concludes that combined VSPerC and LRIPerC enhances cardioprotection compared to either treatment alone. This result is likely attributable to a more potent regulation of inflammation.

  19. Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers

    OpenAIRE

    Grill Warren M; Yoo Paul B; Woock John P

    2010-01-01

    Abstract Background Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES...

  20. Short-latency tachycardia evoked by stimulation of muscle and cutaneous afferents.

    Science.gov (United States)

    Gelsema, A J; Bouman, L N; Karemaker, J M

    1985-04-01

    The short-latency effect on heart rate of peripheral nerve stimulation was studied in decerebrate cats. Selective activation (17-40 microA, 100 Hz, 1 s long) of low-threshold fibers in the nerves to the triceps surae muscle yielded isometric contractions of maximal force that were accompanied by a cardiac cycle length shortening within 0.4 s from the start of stimulation. This effect was abolished by pharmacologically induced neuromuscular blockade. The cardiac cycle length shortening during paralysis reappeared after a 6- to 10-fold increase of the stimulation strength. Cutaneous (sural) nerve stimulation (15-25 microA, 100 Hz, 1 s long) elicited reflex contractions in the stimulated limb, which were also accompanied by a cardiac acceleration with similar latency. Paralysis prevented the reflex contractions and reduced the cardiac response in some cats and abolished it in others. The response reappeared in either case after a 5- to 10-fold increase of the stimulus strength. It is concluded that muscle nerve and cutaneous nerve activity both cause a similar cardiac acceleration with a latency of less than 0.4 s. The response to muscle nerve stimulation is elicited by activity in group III afferents. It is excluded that the cardiac response to nerve stimulation is secondary to a change in the respiratory pattern.

  1. Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

    Science.gov (United States)

    Damelio, F.; Gibbs, M. A.; Mehler, W. R.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

  2. Afferent electrical stimulation during cycling improves spinal processing of sensorimotor function after incomplete spinal cord injury.

    Science.gov (United States)

    Piazza, Stefano; Serrano-Muñoz, Diego; Gómez-Soriano, Julio; Torricelli, Diego; Segura-Fragosa, Antonio; Pons, José Luis; Taylor, Julian

    2017-01-01

    Appropriate afferent feedback delivery during the execution of motor tasks is important for rehabilitation after incomplete spinal cord injury (iSCI). However, during leg-cycling therapy, the plantar afferent feedback is minimal. We hypothesize that the augmentation of sensory input by combining cycling with a locomotor-like stimulation of plantar cutaneous innervations (ES-cycling), might help to restore proper spinal processing of sensorimotor function. Thirteen non-injured subjects and 10 subjects with iSCI performed 10 minutes of cycling and, on another session, of ES-cycling. To assess spinal processing of sensorimotor function, soleus H-reflex response was tested following a conditioning plantar electrical stimulation applied at 25-100 ms inter-stimulus intervals (ISI's), measured before and after the execution of the tasks. Before tasks execution, the conditioned H-reflex response was modulated in non-injured subjects, and absent in subjects with iSCI; after cycling, modulation profiles were unchanged. However, after ES-cycling a significant increase in H-reflex excitability was observed in the non-injured group at 100 ms ISI (p spinal processing of sensorimotor function. Reflex modulation recovery after ES-cycling may indicate the partial reactivation of these mechanisms.

  3. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

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    Caverson, M.M.; Ciriello, J.

    1987-04-01

    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  4. Movement and afferent representations in human motor areas: a simultaneous neuroimaging and transcranial magnetic/peripheral nerve-stimulation study

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    Hitoshi eShitara

    2013-09-01

    Full Text Available Neuroimaging combined with transcranial magnetic stimulation (TMS to primary motor cortex (M1 is an emerging technique that can examine motor-system functionality through evoked activity. However, because sensory afferents from twitching muscles are widely represented in motor areas the amount of evoked activity directly resulting from TMS remains unclear. We delivered suprathreshold TMS to left M1 or electrically stimulated the right median nerve (MNS in 18 healthy volunteers while simultaneously conducting functional magnetic resonance imaging and monitoring with electromyography (EMG. We examined in detail the localization of TMS-, muscle afferent- and superficial afferent-induced activity in M1 subdivisions. Muscle afferent- and TMS-evoked activity occurred mainly in rostral M1, while superficial afferents generated a slightly different activation distribution. In 12 participants who yielded quantifiable EMG, differences in brain activity ascribed to differences in movement-size were adjusted using integrated information from the EMGs. Sensory components only explained 10-20% of the suprathreshold TMS-induced activity, indicating that locally and remotely evoked activity in motor areas mostly resulted from the recruitment of neural and synaptic activity. The present study appears to justify the use of fMRI combined with suprathreshold TMS to M1 for evoked motor network imaging.

  5. Hemicrania Continua-like headache due to nonmetastatic lung cancer--a vagal cephalalgia.

    Science.gov (United States)

    Evans, Randolph W

    2007-10-01

    A 72-year-old man presented with a 7-week history of a new onset constant severe right-sided headache associated with redness and tearing of the right eye, which resolved on indomethacin due to nonmetastatic small cell carcinoma producing a large suprahilar mass. This is the first case report of a hemicrania continua-like headache with autonomic features due to lung cancer. I propose the term "vagal cephalalgia" to include headache and/or facial pain due to nonmetastatic lung cancer and cardiac cephalalgia which result from vagal afferent stimulation.

  6. Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish: cellular organization and neurotransmitters.

    Science.gov (United States)

    Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E

    2009-09-20

    The sense of taste is crucial in an animal's determination as to what is edible and what is not. This gustatory function is especially important in goldfish, who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe, which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons that have radially directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca(++)-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (+/-)-alpha-amino-3-hydroxy- 5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediate neurotransmission between reflex interneurons and vagal motoneurons. Thus, the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system.

  7. Acute Exposure to Terrestrial Trunked Radio (TETRA) has effects on the electroencephalogram and electrocardiogram, consistent with vagal nerve stimulation.

    Science.gov (United States)

    Burgess, Adrian P; Fouquet, Nathalie C; Seri, Stefano; Hawken, Malcolm B; Heard, Andrew; Neasham, David; Little, Mark P; Elliott, Paul

    2016-10-01

    Terrestrial Trunked Radio (TETRA) is a telecommunications system widely used by police and emergency services around the world. The Stewart Report on mobile telephony and health raised questions about possible health effects associated with TETRA signals. This study investigates possible effects of TETRA signals on the electroencephalogram and electrocardiogram in human volunteers. Blinded randomized provocation study with a standardized TETRA signal or sham exposure. In the first of two experiments, police officers had a TETRA set placed first against the left temple and then the upper-left quadrant of the chest and the electroencephalogram was recorded during rest and active cognitive processing. In the second experiment, volunteers were subject to chest exposure of TETRA whilst their electroencephalogram and heart rate variability derived from the electrocardiogram were recorded. In the first experiment, we found that exposure to TETRA had consistent neurophysiological effects on the electroencephalogram, but only during chest exposure, in a pattern suggestive of vagal nerve stimulation. In the second experiment, we observed changes in heart rate variability during exposure to TETRA but the electroencephalogram effects were not replicated. Observed effects of exposure to TETRA signals on the electroencephalogram (first experiment) and electrocardiogram are consistent with vagal nerve stimulation in the chest by TETRA. However given the small effect on heart rate variability and the lack of consistency on the electroencephalogram, it seems unlikely that this will have a significant impact on health. Long-term monitoring of the health of the police force in relation to TETRA use is on-going. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Low-frequency stimulation of group III and IV hind limb afferents evokes reflex pressor responses in decerebrate rats.

    Science.gov (United States)

    Harms, Jonathan E; Copp, Steven W; Kaufman, Marc P

    2016-10-01

    Contraction of freely perfused hind limb muscles in decerebrate rats evokes the exercise pressor reflex, resulting in sympathetic activation and increased blood pressure. This reflex is propagated along mechanically sensitive group III and metabolically sensitive group IV afferent nerve fibers. Recent research by our laboratory has focused on the exaggeration of the exercise pressor reflex in decerebrate rats with simulated peripheral artery disease, which was induced by ligating the femoral artery for 72 h before the start of the experiment. Recently, we showed that ligating the femoral artery increased the responses of single fiber group III and IV triceps surae muscle afferents to static contraction. The objective of this study was to determine if electrical stimulation of group III and IV afferents at frequencies approximating those occurring during static contraction was capable of reflexively increasing arterial blood pressure. We directly stimulated muscle afferents in the absence of muscle contraction for both freely perfused and ligated rats. We established 0.25 Hz as the minimal stimulation frequency to observe a sustained blood pressure response. The blood pressure response increased in a graded fashion as both stimulus frequency and motor threshold were increased. Additionally, we observed similar blood pressure responses from both freely perfused and ligated rats, suggesting that spinal and medullary processing of group III and IV afferent input plays no role in augmenting the pressor response to contraction caused by femoral artery ligation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  9. Synaptic depression in the CA1 region of freely behaving mice is highly dependent on afferent stimulation parameters

    Directory of Open Access Journals (Sweden)

    Jinzhong Jeremy Goh

    2013-01-01

    Full Text Available Persistent synaptic plasticity has been subjected to intense study in the decades since it was first described. Occurring in the form of long-term potentiation (LTP and long-term depression (LTD, it shares many cellular and molecular properties with hippocampus-dependent forms of persistent memory. Recent reports of both LTP and LTD occurring endogenously under specific learning conditions provide further support that these forms of synaptic plasticity may comprise the cellular correlates of memory. Most studies of synaptic plasticity are performed using in vitro or in vivo preparations where patterned electrical stimulation of afferent fibers is implemented to induce changes in synaptic strength. This strategy has proven very effective in inducing LTP, even under in vivo conditions. LTD in vivo has proven more elusive: although LTD occurs endogenously under specific learning conditions in both rats and mice, its induction in mice in the CA1 region has not been successfully demonstrated with afferent electrical stimulation alone. In this study we screened a large spectrum of protocols that are known to induce LTD either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo. Low frequency stimulation at 1, 2, 3, 5, 7 or 10 Hz given in the range of 100 through 1800 pulses produced, at best, short-term depression that lasted for up to 60 min. Varying the administration pattern of the stimuli (e.g. 900 pulses given twice at 5 min intervals, or changing the stimulation intensity did not improve the persistency of synaptic depression. LTD that lasts for at least 24h occurs under learning conditions in mice. We conclude that a coincidence of factors, such as afferent activity together with neuromodulatory inputs, play a decisive role in the enablement of LTD under more naturalistic (e.g. learning conditions.

  10. Different frequencies of transcutaneous electrical nerve stimulation on sympatho-vagal balance

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    Angélica Trevisan de Nardi

    2017-05-01

    Full Text Available This study aims to evaluate the effects of TENS at different frequencies on autonomic balance in healthy volunteers. It is a case-control study, and was composed of fourteen healthy volunteers (5 women with 28 (3.9 years old who underwent low (10 Hz 200ms-1 and high (100 Hz 200ms-1 frequency TENS. The interventions were randomized and applied for 30 minutes in the trajectory brachial nerve plexus from non-dominant member. Intensities were adjusted every 5 minutes and maintained below motor threshold. The autonomic balance was assessed before and after interventions by heart rate variability (HRV. TENS 10 Hz increased 10% sympathetic activity and decreased 10% parasympathetic activity; however, TENS 100 Hz showed opposite effects (p < 0.05. The sympatho-vagal balance increased with low frequency TENS and decreased with high frequency (p < 0.05. It can be concluded that different frequencies of TENS applied in the trajectory brachial nerve plexus modify cardiovascular autonomic responses. High frequency TENS reduces sympathetic activity and increases the parasympathetic, which favors beneficial effects on autonomic balance in healthy volunteers.

  11. Relation Between the Frequency of Short-Pulse Electrical Stimulation of Afferent Nerve Fibers and Evoked Muscle Force.

    Science.gov (United States)

    Dideriksen, Jakob; Leerskov, Kasper; Czyzewska, Magdalena; Rasmussen, Rune

    Objective: Functional electrical stimulation (FES) is conventionally performed by the stimulation of motor axons causing the muscle fibers innervated by these axons to contract. An alternative strategy that may evoke contractions with more natural motor unit behavior is to stimulate afferent fibers (primarily type Ia) to excite the motor neurons at the spinal level. The aim of the study was to investigate the range of forces that can be evoked in this way and the degree to which the torque can be controlled. Methods: We stimulated the tibial nerve of ten healthy participants at amplitudes at which the highest H-reflex with minimal M-wave was present. The evoked plantar flexion torque was recorded following short stimulation pulses (0.4 ms) with frequencies ranging from 20 to 200 Hz. Results: Across all subjects, the median highest evocable torque was 38.3% (quartiles: 16.9-51.0) of the maximum voluntary contraction torque (MVC). The average torque variability (standard deviation) was 1.7 +/- 0.7% MVC. For most subjects, the relation between stimulation frequency and evoked torque was well characterized by sigmoidal curves (median root mean square error: 6.4% MVC). The plateau of this sigmoid curve (indicating the range of frequencies over which torque amplitude could be modulated) was reached at 56.0 (quartiles: 29.4-81.9) Hz. Conclusion: Using the proposed method for FES, substantial evoked torques that could be controlled by stimulation frequency were achieved. Significance: Stimulation of afferent fibers could be a useful and fatigue-resistant strategy for several applications of FES.Objective: Functional electrical stimulation (FES) is conventionally performed by the stimulation of motor axons causing the muscle fibers innervated by these axons to contract. An alternative strategy that may evoke contractions with more natural motor unit behavior is to stimulate afferent fibers (primarily type Ia) to excite the motor neurons at the spinal level. The aim of the

  12. The role of cutaneous afferents in controlling locomotion evoked by epidural stimulation of the spinal cord in decerebrate cats.

    Science.gov (United States)

    Dorofeev, I Yu; Avelev, V D; Shcherbakova, N A; Gerasimenko, Yu P

    2008-09-01

    The effects of the cutaneous input on the formation of the locomotor pattern in conditions of epidural stimulation of the spinal cord in decerebrate cats were studied. Locomotor activity was induced by rhythmic stimulation of the dorsal surface of spinal cord segments L4-L5 at a frequency of 3-5 Hz. Electromyograms (EMG) recorded from the antagonist muscles quadriceps, semitendinosus, tibialis anterior, and gastrocnemius lateralis were recorded, along with the kinematics of stepping movements during locomotion on a moving treadmill and reflex responses to single stimuli. Changes in the pattern of reactions observed before and after exclusion of cutaneous receptors (infiltration of lidocaine solution at the base of the paw or irrigation of the paw pads with chlorothane solution) were assessed. This treatment led to impairment of the locomotor cycle: the paw was placed with the rear surface downward and was dragged along in the swing phase, and the duration of the stance phase decreased. Exclusion of cutaneous afferents suppressed the polysynaptic activity of the extensor muscles and the distal flexor muscle of the ipsilateral hindlimb during locomotion evoked by epidural stimulation of the spinal cord. The effects of exclusion of cutaneous afferents on the monosynaptic component of the EMG response were insignificant.

  13. The "vagal ansa": a source of complication in vagus nerve stimulation.

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    Gopalakrishnan, Chittur Viswanathan; Kestle, John R W; Connolly, Mary B

    2015-05-01

    A 16-year-old boy underwent vagus nerve stimulation for treatment-resistant multifocal epilepsy. During intraoperative system diagnostics, vigorous contraction of the ipsilateral sternomastoid muscle was observed. On re-exploration, a thin nerve fiber passing from the vagus to the sternomastoid was found hooked up in the upper electrode. Detailed inspection revealed an abnormal course of the superior root of the ansa cervicalis, which descended down as a single nerve trunk with the vagus and separated to join the inferior root. The authors discuss the variation in the course of the ansa cervicalis and how this could be a reason for postoperative neck muscle contractions.

  14. Vagal reflex stimulation complicating retrieval of an unusual foreign body from the laryngotracheal lumen: Case report

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    H.K. Omokanye

    2016-04-01

    Full Text Available Foreign body impaction in the aero digestive tract is a life-threatening emergency, particularly in the paediatric age group. Removal under general anaesthesia poses both surgical and anaesthetic challenges and this may rarely result in mortality. We report a case of a 4 year old boy with an unusual foreign body (FB impacted in the laryngotracheal causing difficult intubation and precluding tracheostomy with attendant vasovagal reflex stimulation and cardiac arrest. Clinical presentation and radiological evaluation of the patient were highlighted with a review of pertinent literature. We conclude that dis-impacting a foreign body in the trachea could potentiate bradycardia and cardiac arrest; co-existing hypercarbia and/or sepsis increase the risk and worsen the prognosis.

  15. Afferent and motoneuron activity in response to single neuromast stimulation in the posterior lateral line of larval zebrafish.

    Science.gov (United States)

    Haehnel-Taguchi, Melanie; Akanyeti, Otar; Liao, James C

    2014-09-15

    The lateral line system of fishes contains mechanosensory receptors along the body surface called neuromasts, which can detect water motion relative to the body. The ability to sense flow informs many behaviors, such as schooling, predator avoidance, and rheotaxis. Here, we developed a new approach to stimulate individual neuromasts while either recording primary sensory afferent neuron activity or swimming motoneuron activity in larval zebrafish (Danio rerio). Our results allowed us to characterize the transfer functions between a controlled lateral line stimulus, its representation by primary sensory neurons, and its subsequent behavioral output. When we deflected the cupula of a neuromast with a ramp command, we found that the connected afferent neuron exhibited an adapting response which was proportional in strength to deflection velocity. The maximum spike rate of afferent neurons increased sigmoidally with deflection velocity, with a linear range between 0.1 and 1.0 μm/ms. However, spike rate did not change when the cupula was deflected below 8 μm, regardless of deflection velocity. Our findings also reveal an unexpected sensitivity in the larval lateral line system: stimulation of a single neuromast could elicit a swimming response which increased in reliability with increasing deflection velocities. At high deflection velocities, we observed that lateral line evoked swimming has intermediate values of burst frequency and duty cycle that fall between electrically evoked and spontaneous swimming. An understanding of the sensory capabilities of a single neuromast will help to build a better picture of how stimuli are encoded at the systems level and ultimately translated into behavior. Copyright © 2014 the American Physiological Society.

  16. Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1996-01-01

    arterioles with the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was equally enhanced by omission of extracellular calcium and by addition of 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. The stimulatory effects of low calcium [with......Calcium-activated chloride channels have been proposed to control renin release from juxtaglomerular cells and to be involved in the excitation-contraction coupling of the renal afferent arteriole. The hypothesis was tested on renin release from rat glomeruli and in microperfused rabbit afferent...... or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate...

  17. The physiological motor patterns produced by neurons in the nucleus retroambiguus in the rat and their modulation by vagal, peripheral chemosensory, and nociceptive stimulation.

    Science.gov (United States)

    Subramanian, Hari H; Huang, Zheng-Gui; Silburn, Peter A; Balnave, Ron J; Holstege, Gert

    2018-02-01

    The nucleus retroambiguus (NRA) is a neuronal cell group in the medullary ventrolateral tegmentum, rostrocaudally between the obex and the first cervical spinal segment. NRA neurons are premotor interneurons with direct projections to the motoneurons of soft palate, pharynx, and larynx in the nucleus ambiguus in the lateral medulla as well as to the motoneurons in the spinal cord innervating diaphragm, abdominal, and pelvic floor muscles and the lumbosacral motoneurons generating sexual posture. These NRA premotor interneurons receive very strong projections from the periaqueductal gray (PAG) in the context of basic survival mechanisms as fight, flight, freezing, sound production, and sexual behavior. In the present study in rat we investigated the physiological motor patterns generated by NRA neurons, as the result of vagal, peripheral chemosensory, and nociceptive stimulation. The results show that the NRA contains phasic respiratory modulated neurons, as well as nonphasic tonically modulated neurons. Stimulation in the various rostrocaudal levels of the NRA generates site-specific laryngeal, respiratory, abdominal, and pelvic floor motor activities. Vagal and peripheral chemosensory stimulation induces both excitatory and inhibitory modulation of phasic NRA-neurons, while peripheral chemosensory and nociceptive stimulation causes excitation and inhibition of nonphasic NRA-neurons. These results are in agreement with the concept that the NRA represents a multifunctional group of neurons involved in the output of the emotional motor system, such as vomiting, vocalization, mating, and changes in respiration. © 2017 Wiley Periodicals, Inc.

  18. Does patterned afferent stimulation of sacral dermatomes suppress urethral sphincter reflexes in individuals with spinal cord injury?

    Science.gov (United States)

    McCoin, Jaime L; Bhadra, Narendra; Brose, Steven W; Gustafson, Kenneth J

    2015-03-01

    Dyssynergic contractions of the external urethral sphincter prevent efficient bladder voiding and lead to numerous health concerns. Patterned electrical stimulation of the sacral dermatomes reduces urethral sphincter spasms and allows functional bladder emptying in cats after chronic SCI. Reflex suppression in animals is strongly dependent on stimulus location and pattern. The purpose of this study was to determine whether the stimulation patterns and locations effective in animals suppress urethral sphincter spasms in humans with SCI. Ten subjects with chronic SCI underwent bladder filling to elicit distention-evoked contractions. During reflex contractions patterned electrical stimulation was applied to the S2 or S3 dermatome in random 25-sec intervals. Bladder and sphincter pressures were simultaneously recorded and compared between control and afferent stimulation periods. Six of the 10 subjects demonstrated both reflex bladder and sphincter contractions with bladder filling. No significant reduction in urethral pressure was observed during stimulation for any stimulus locations and patterns tested. Stimulation parameters and locations effective in SCI animals did not suppress reflex sphincter activity in these human subjects. It is likely that a broader set of stimulus patterns and dermatome locations will need to be tested to find the effective combination in humans. © 2014 Wiley Periodicals, Inc.

  19. Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

    Science.gov (United States)

    Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

    2014-01-01

    Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other

  20. Scalp-recorded evoked potentials as a marker for afferent nerve impulse in clinical vagus nerve stimulation.

    Science.gov (United States)

    Usami, Kenichi; Kawai, Kensuke; Sonoo, Masahiro; Saito, Nobuhito

    2013-07-01

    Vagus nerve stimulation (VNS) is a palliative treatment for drug resistant epilepsy for which the efficacy and safety are well established. Accumulating evidence suggests that ascending vagal signals modulate abnormal cortical excitability via various pathways. However, there is no direct evidence for an ascending conduction of neural impulses in a clinical case of VNS. We recorded and analyzed the short-latency components of the vagus nerve (VN) evoked potential (EP) from the viewpoint of determining whether or not it is a marker for the ascending neural conduction. EPs within 20 ms were prospectively recorded simultaneously from a surgical wound in the neck and at multiple scalp sites during implantation surgery in 25 patients with drug-resistant epilepsy. Electrical stimulation was delivered using the clinical VNS Therapy system. A recording was made before and after a muscle relaxant was administered, when changing the rostrocaudal position of stimulation, or when stimulating the ansa cervicalis instead of the VN. The short-latency components consisted of four peaks. The early component around 3 ms, which was most prominent in A1-Cz, remained unchanged after muscle relaxation while the later peaks disappeared. Rostral transition of the stimulation resulted in an earlier shift of the early component. The estimated conduction velocity was 27.4 ± 10.2 m/s. Stimulation of the ansa cervicalis induced no EP. The early component was regarded as directly resulting from ascending neural conduction of A fibers of the VN, probably originating around the jugular foramen. Recording of VN-EP might document the cause of treatment failure in some patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

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    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  2. Vagal Nerve Stimulation

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    Hakan Ekmekçi

    2017-05-01

    CONCLUSION: VNS, which is a treatment modality that will take place it deserves in epilepsy treatment with "the correct patient" and "correct reason", must be known better and its applications must be developed.

  3. Assessing sensorimotor excitability after spinal cord injury: a reflex testing method based on cycling with afferent stimulation.

    Science.gov (United States)

    Piazza, Stefano; Torricelli, Diego; Gómez-Soriano, Julio; Serrano-Muñoz, Diego; Ávila-Martín, Gerardo; Galán-Arriero, Iriana; Pons, José Luis; Taylor, Julian

    2018-01-17

    Several studies have examined spinal reflex modulation during leg cycling in healthy and spinal cord injury (SCI) subjects. However, the effect of cutaneous plantar afferent input on spinal excitability during leg cycling after SCI has not been characterised. The aim of the study was to test the feasibility of using controlled leg cycling in combination with plantar cutaneous electrical stimulation (ES) cycling to assess lower limb spinal sensorimotor excitability in subjects with motor complete or incomplete SCI. Spinal sensorimotor excitability was estimated by measuring cutaneomuscular-conditioned soleus H-reflex activity. Reflex excitability was tested before and after a 10-min ES cycling session in 13 non-injured subjects, 6 subjects with motor incomplete SCI (iSCI) who had moderately impaired gait function, 4 subjects with motor iSCI who had severely impaired gait function, and 5 subjects with motor complete SCI (cSCI). No modulation of soleus H-reflex with plantar cutaneous stimuli was observed after either iSCI or cSCI when compared to non-injured subjects. However, after ES cycling, reflex excitability significantly increased in subjects with iSCI and moderately impaired gait function. ES cycling facilitated spinal sensorimotor excitability only in subjects with motor iSCI with residual gait function. Increased spinal excitability induced with a combination of exercise and afferent stimulation could be adopted with diagnostic and prognostic purposes to reveal the activity-based neurorehabilitation profile of individual subjects with motor iSCI. ISRCTN 26172500 ; retrospectively registered on 15 July 2016 Graphical abstract ᅟ.

  4. In vivo release by vagal stimulation of L-/sup 3/Hglutamic acid in the nucleus tractus solitarius preloaded with L-/sup 3/Hglutamine

    Energy Technology Data Exchange (ETDEWEB)

    Granata, A.R.; Sved, A.F.; Reis, D.J.

    1984-01-01

    In anesthetized and paralyzed rats, using a push-pull perfusion technique, we examined the effect of bilateral vagal stimulation on the release of L-/sup 3/Hglutamic acid (L-/sup 3/HGlu) from the nucleus tractus solitarius (NTS), after preloading the tissue either with L-/sup 3/HGlu or L-/sup 3/Hglutamine (L-/sup 3/HGln). Vagal stimulation sufficient to produce a maximum fall of arterial pressure (AP) evoked release of L-/sup 3/HGlu from the NTS when the tissue was preloaded with either /sup 3/H-Glu or /sup 3/H-Gln, and of D-/sup 3/Haspartic acid (D-/sup 3/HAsp) when this stable Glu analogue was used to preloaded with either /sup 3/H-Glu or /sup 3/H-Gln, and of D-/sup 3/H precursor L-Gln is a good marker of the releasable pool of L-Glu in vivo and are consistent with the hypothesis that L-/sup 3/HGlu is a neurotransmitter in the NTS, mediating the vasodepressor response from cardiopulmonary mechanoreceptors.

  5. High frequency stimulation of the subthalamic nucleus leads to presynaptic GABA(B-dependent depression of subthalamo-nigral afferents.

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    Anton Dvorzhak

    Full Text Available Patients with akinesia benefit from chronic high frequency stimulation (HFS of the subthalamic nucleus (STN. Among the mechanisms contributing to the therapeutic success of HFS-STN might be a suppression of activity in the output region of the basal ganglia. Indeed, recordings in the substantia nigra pars reticulata (SNr of fully adult mice revealed that HFS-STN consistently produced a reduction of compound glutamatergic excitatory postsynaptic currents at a time when the tetrodotoxin-sensitive components of the local field potentials had already recovered after the high frequency activation. These observations suggest that HFS-STN not only alters action potential conduction on the way towards the SNr but also modifies synaptic transmission within the SNr. A classical conditioning-test paradigm was then designed to better separate the causes from the indicators of synaptic depression. A bipolar platinum-iridium macroelectrode delivered conditioning HFS trains to a larger group of fibers in the STN, while a separate high-ohmic glass micropipette in the rostral SNr provided test stimuli at minimal intensity to single fibers. The conditioning-test interval was set to 100 ms, i.e. the time required to recover the excitability of subthalamo-nigral axons after HFS-STN. The continuity of STN axons passing from the conditioning to the test sites was examined by an action potential occlusion test. About two thirds of the subthalamo-nigral afferents were occlusion-negative, i.e. they were not among the fibers directly activated by the conditioning STN stimulation. Nonetheless, occlusion-negative afferents exhibited signs of presynaptic depression that could be eliminated by blocking GABA(B receptors with CGP55845 (1 µM. Further analysis of single fiber-activated responses supported the proposal that the heterosynaptic depression of synaptic glutamate release during and after HFS-STN is mainly caused by the tonic release of GABA from co-activated striato

  6. Patient controlled versus automatic stimulation of pudendal nerve afferents to treat neurogenic detrusor overactivity.

    Science.gov (United States)

    Opisso, E; Borau, A; Rodríguez, A; Hansen, J; Rijkhoff, N J M

    2008-10-01

    We investigated whether patients with neurogenic detrusor overactivity can sense the onset of bladder contraction and in turn suppress the contraction by electrical stimulation of the dorsal penile-clitoral nerve. A total of 67 patients with different neurological disorders were recruited to undergo 3 filling cystometries. The first cystometry was done without stimulation. The second cystometry was performed with automatic controlled stimulation based on detrusor pressure. The third cystometry was done with patient controlled stimulation using a push button. Four females and 13 males underwent all 3 fillings. Compared to cystometry 1 average bladder capacity for cystometries 2 and 3 was 60% higher. Compared to peak pressure for cystometry 1 average peak pressure during suppressed contractions for cystometries 2 and 3 was 49% and 26% lower, respectively. The average delay of the onset of stimulation during cystometry 3 with respect to cystometry 2 was 5.7 seconds. The study shows that patient controlled genital nerve stimulation is as effective as automatic controlled stimulation to treat neurogenic detrusor overactivity. Thus, patient controlled stimulation is feasible in select patients, although patients must be trained in the technique.

  7. Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence

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    Damon G. Lamb

    2017-07-01

    Full Text Available Posttraumatic stress disorder (PTSD is a reaction to trauma that results in a chronic perception of threat, precipitating mobilization of the autonomic nervous system, and may be reflected by chronic disinhibition of limbic structures. A common injury preceding PTSD in veterans is mild traumatic brain injury (mTBI. This may be due to the vulnerability of white matter in these networks and such damage may affect treatment response. We evaluated transcutaneous vagal nerve stimulation (tVNS, a non-invasive, low-risk approach that may alter the functions of the limbo-cortical and peripheral networks underlying the hyperarousal component of PTSD and thus improve patient health and well-being. In this single visit pilot study evaluating the impact of tVNS in 22 combat veterans, we used a between-subjects design in people with either PTSD with preceding mTBI or healthy controls. Participants were randomized into stimulation or sham groups and completed a posturally modulated autonomic assessment and emotionally modulated startle paradigm. The primary measures used were respiratory sinus arrhythmia (high-frequency heart rate variability during a tilt-table procedure derived from an electrocardiogram, and skin conductance changes in response to acoustic startle while viewing emotional images (International Affective Picture System. The stimulation was well tolerated and resulted in improvements in vagal tone and moderation of autonomic response to startle, consistent with modulation of autonomic state and response to stress in this population. Our results suggest that tVNS affects systems underlying emotional dysregulation in this population and, therefore, should be further evaluated and developed as a potential treatment tool for these patients.

  8. Modulation of local field potentials by high-frequency stimulation of afferent axons in the hippocampal CA1 region.

    Science.gov (United States)

    Yu, Ying; Feng, Zhouyan; Cao, Jiayue; Guo, Zheshan; Wang, Zhaoxiang; Hu, Na; Wei, Xuefeng

    2016-03-01

    Modulation of the rhythmic activity of local field potentials (LFP) in neuronal networks could be a mechanism of deep brain stimulation (DBS). However, exact changes of LFP during the periods of high-frequency stimulation (HFS) of DBS are unclear because of the interference of dense stimulation artifacts with high amplitudes. In the present study, we investigated LFP changes induced by HFS of afferent axons in the hippocampal CA1 region of urethane-anesthetized rats by using a proper algorithm of artifact removal. Afterward, the LFP changes in the frequency bands of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] rhythms were studied by power spectrum analysis and coherence analysis for the recorded signals collected in the pyramidal layer and in the stratum radiatum of CA1 region before, during and after 1-min long 100 and 200[Formula: see text]Hz HFS. Results showed that the power of LFP rhythms in higher-frequency band ([Formula: see text] rhythm) increased in the pyramidal layer and the power of LFP rhythms in lower-frequency bands ([Formula: see text], [Formula: see text] and [Formula: see text] rhythms) decreased in the stratum radiatum during HFS. The synchronization of [Formula: see text] rhythm decreased and the synchronization of [Formula: see text] rhythm increased during HFS in the stratum radiatum. These results suggest that axonal HFS could modulate LFP rhythms in the downstream brain areas with a plausible underlying mechanism of partial axonal blockage induced by HFS. The study provides new evidence to support the mechanism of DBS modulating rhythmic activity of neuronal populations.

  9. Distinct target cell-dependent forms of short-term plasticity of the central visceral afferent synapses of the rat

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    Watabe Ayako M

    2010-10-01

    Full Text Available Abstract Background The visceral afferents from various cervico-abdominal sensory receptors project to the dorsal vagal complex (DVC, which is composed of the nucleus of the solitary tract (NTS, the area postrema and the dorsal motor nucleus of the vagus nerve (DMX, via the vagus and glossopharyngeal nerves and then the solitary tract (TS in the brainstem. While the excitatory transmission at the TS-NTS synapses shows strong frequency-dependent suppression in response to repeated stimulation of the afferents, the frequency dependence and short-term plasticity at the TS-DMX synapses, which also transmit monosynaptic information from the visceral afferents to the DVC neurons, remain largely unknown. Results Recording of the EPSCs activated by paired or repeated TS stimulation in the brainstem slices of rats revealed that, unlike NTS neurons whose paired-pulse ratio (PPR is consistently below 0.6, the distribution of the PPR of DMX neurons shows bimodal peaks that are composed of type I (PPR, 0.6-1.5; 53% of 120 neurons recorded and type II (PPR, Conclusions These two general types of short-term plasticity might contribute to the differential activation of distinct vago-vagal reflex circuits, depending on the firing frequency and type of visceral afferents.

  10. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  11. Stimulation of trigeminal afferents improves motor recovery after facial nerve injury: functional, electrophysiological and morphological proofs.

    Science.gov (United States)

    Skouras, Emmanouil; Pavlov, Stoyan; Bendella, Habib; Angelov, Doychin N

    2013-01-01

    Recovery of mimic function after facial nerve transection is poor: the successful regrowth of axotomized motoneurons to their targets is compromised by (1) poor axonal navigation and excessive collateral branching, (2) abnormal exchange of nerve impulses between adjacent regrowing axons, and (3) insufficient synaptic input to facial motoneurons. As a result, axotomized motoneurons get hyperexcitable and unable to discharge. Since improvement of growth cone navigation and reduction of the ephaptic cross talk between axons turn out be very difficult, we concentrated our efforts on the third detrimental component and proposed that an intensification of the trigeminal input to axotomized electrophysiologically silent facial motoneurons might improve specificity of reinnervation. To test our hypothesis we compared behavioral, electrophysiological, and morphological parameters after single reconstructive surgery on the facial nerve (or its buccal branch) with those obtained after identical facial nerve surgery but combined with direct or indirect stimulation of the ipsilateral infraorbital (ION) nerve. We found that in all cases, trigeminal stimulation was beneficial for the outcome by improving the quality of target reinnervation and recovery of vibrissa! motor performance.

  12. Acute inhalation of ozone stimulates bronchial C-fibers and rapidly adapting receptors in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Coleridge, J.C.G.; Coleridge, H.M.; Schelegle, E.S.; Green, J.F. (Univ. of California, Davis (United States) Univ. of California, San Francisco (United States))

    1993-05-01

    To identify the afferents responsible for initiating the vagally mediated respiratory changes evoked by acute exposure to ozone, the authors recorded vagal impulses in anesthetized, open-chest, artificially ventilated dogs and examined the pulmonary afferent response to ozone (2--3 ppM in air) delivered to the lower trachea for 20--60 min. Bronchial C-fibers (BrCs) were the lung afferents most susceptible to ozone, the activity of 10 of 11 BrCs increasing from 0.2 [+-] 0.2 to 4.6 [+-] 1.3 impulses/s within 1--7 min of ozone exposure. Ten of 15 rapidly adapting receptors (RARs) were stimulated by ozone, their activity increasing from 1.5 [+-] 0.4 to 4.7 [+-] 0.7 impulses/s. Stimulation of RARs (but not of BrCs) appeared secondary to the ozone-induced reduction of lung compliance because it was abolished by hyperinflation of the lungs. Ozone had little effect on pulmonary C-fibers or slowly adapting pulmonary stretch receptors. The authors' results suggest that both BrCs and RARs contribute to the tachypnea and bronchoconstriction evoked by acute exposure to ozone when vagal conduction is intact and that BrCs alone are responsible for the vagally mediated tachypnea that survives vagal cooling to 7[degrees]C. 23 refs., 5 figs.

  13. Effects of subthalamic nucleus lesions and stimulation upon corticostriatal afferents in the 6-hydroxydopamine-lesioned rat

    National Research Council Canada - National Science Library

    Walker, Ruth H; Moore, Cindy; Davies, Georgia; Dirling, Lisa B; Koch, Rick J; Meshul, Charles K

    2012-01-01

    ... or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate...

  14. Combining afferent stimulation and mirror therapy for rehabilitating motor function, motor control, ambulation, and daily functions after stroke.

    Science.gov (United States)

    Lin, Keh-chung; Huang, Pai-chuan; Chen, Yu-ting; Wu, Ching-yi; Huang, Wen-ling

    2014-02-01

    Mirror therapy (MT) and mesh glove (MG) afferent stimulation may be effective in reducing motor impairment after stroke. A hybrid intervention of MT combined with MG (MT + MG) may broaden aspects of treatment benefits. To demonstrate the comparative effects of MG + MT, MT, and a control treatment (CT) on the outcomes of motor impairments, manual dexterity, ambulation function, motor control, and daily function. Forty-three chronic stroke patients with mild to moderate upper extremity impairment were randomly assigned to receive MT + MG, MT, or CT for 1.5 hours/day, 5 days/week for 4 weeks. Outcome measures were the Fugl-Meyer Assessment (FMA) and muscle tone measured by Myoton-3 for motor impairment and the Box and Block Test (BBT) and 10-Meter Walk Test (10 MWT) for motor function. Secondary outcomes included kinematic parameters for motor control and the Motor Activity Log and ABILHAND Questionnaire for daily function. FMA total scores were significantly higher and synergistic shoulder abduction during reach was less in the MT + MG and MT groups compared with the CT group. Performance on the BBT and the 10 MWT (velocity and stride length in self-paced task and velocity in as-quickly-as-possible task) were improved after MT + MG compared with MT. MT + MG improved manual dexterity and ambulation. MT + MG and MT reduced motor impairment and synergistic shoulder abduction more than CT. Future studies may integrate functional task practice into treatments to enhance functional outcomes in patients with various levels of motor severity. The long-term effects of MG + MT remain to be evaluated.

  15. Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

    Science.gov (United States)

    Doeltgen, Sebastian H; Young, Jessica; Bradnam, Lynley V

    2016-08-01

    The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

  16. Urinary bladder irritation alters efficacy of vagal stimulation on rostral medullary neurons in chronic T8 spinalized rats.

    Science.gov (United States)

    Kaddumi, Ezidin G; Hubscher, Charles H

    2007-07-01

    The presence of pelvic visceral inputs to neurons in the rostral medulla that are responsive to electrical stimulation of the abdominal branches of the vagus nerve (VAG-abd) was investigated in a complete chronic T8 spinal transection rat model. Using extracellular electrophysiological recordings from single medullary reticular formation (MRF) neurons, 371 neurons in 15 rats responsive to pinching the ear (search stimulus) were tested for somato-visceral and viscero-visceral convergent responses to stimulation of the following nerves/territories: VAG-abd, dorsal nerve of the penis, pelvic nerve, distention of urinary bladder and colon, penile stimulation, urethral infusion, and touch/pinch of the entire body surface. In addition to these mechanical and electrical stimuli, a chemical stimulus applied to the bladder was assessed as well. Of the total neurons examined, 205 were tested before and 166 tested beginning 20 min after application of a chemical irritant (2% acetic acid) to the urinary bladder (same rats used pre/post irritation). As with intact controls, many ear-responsive MRF neurons responded to the electrical stimulation of VAG-abd. Although MRF neuron responses failed to be evoked with direct (mechanical and electrical nerve) pelvic visceral stimuli, acute chemical irritation of the urinary bladder produced a significant increase in the number of MRF neurons responsive to stimulation of VAG-abd. The results of this study indicate a central effect that potentially relates to some of the generalized below level pelvic visceral sensations that have been documented in patients with complete spinal cord injury.

  17. Renal Afferents.

    Science.gov (United States)

    Frame, Alissa A; Carmichael, Casey Y; Wainford, Richard D

    2016-09-01

    The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the renal sympathetic nerves. The renal sympathetic nerves, which are comprised of both afferent (sensory input) and efferent (sympathetic outflow) arms, have emerged as a major potential therapeutic target to treat hypertension and disease states exhibiting excess renal sympathetic activity. This review highlights recent advances in both clinical and basic science that have provided new insight into the distribution, function, and reinnervation of the renal sympathetic nerves, with a focus on the renal afferent nerves, in hypertension and hypertension-evoked disease states including salt-sensitive hypertension, obesity-induced hypertension, and chronic kidney disease. Increased understanding of the differential role of the renal afferent versus efferent nerves in the pathophysiology of hypertension has the potential to identify novel targets and refine therapeutic interventions designed to treat hypertension.

  18. Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro.

    Directory of Open Access Journals (Sweden)

    Francesco Dose

    Full Text Available Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in

  19. Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro.

    Science.gov (United States)

    Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

    2014-01-01

    Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other

  20. Tachykinins mediate vagal inhibition of gastrin secretion in pigs

    DEFF Research Database (Denmark)

    Schmidt, P; Poulsen, Steen Seier; Hilsted, L

    1996-01-01

    Electrical vagal stimulation activates both stimulatory and inhibitory nerve fibers regulating gastrin release in the porcine antrum. The aim of this study was to examine the role of tachykinins in the inhibitory vagal control of gastrin release in the porcine antrum....

  1. Use of social media to assess the effectiveness of vagal nerve stimulation in Dravet syndrome: A caregiver's perspective.

    Science.gov (United States)

    Ali, Rushna; Elsayed, Mona; Kaur, Manpreet; Air, Ellen; Mahmood, Naznin; Constantinou, Jules; Schwalb, Jason

    2017-04-15

    Dravet syndrome (DS) is a rare genetic epilepsy syndrome which is particularly pharmacoresistant. Vagus nerve stimulation (VNS) is commonly used in the treatment of DS as an adjunct to medical therapy. A meaningful assessment of post-surgical outcomes with VNS is difficult given the rarity of the condition. In a novel approach, we used social media to contact patients with DS to gather data on post-surgical seizure reduction and overall satisfaction with VNS. A survey consisting of 10 questions was posted to a social media webpage for a DS support group moderated by the Dravet Syndrome Foundation. The results were analyzed and percentages reported using the integrated SurveyMonkey analytical software. 49 responses were received. We found that 28.5% of patients had a >50% reduction in seizure frequency after VNS placement, 55.8% felt that VNS therapy had helped to reduce seizure frequency, and 83.7% felt that seizure severity had improved. Of the respondents, 75% felt that they would undergo VNS implantation again for similar outcomes. We employed the novel technique of using social media to gather the largest set of self-reported outcomes of VNS therapy for Dravet syndrome. As corroborated by prior studies of VNS effectiveness in Dravet syndrome, there is significant albeit limited improvement in seizure control. Our study shows that despite this limitation, it is still considered a useful treatment adjunct from a caregiver's perspective. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Vagal Sensory Neuron Subtypes that Differentially Control Breathing.

    Science.gov (United States)

    Chang, Rui B; Strochlic, David E; Williams, Erika K; Umans, Benjamin D; Liberles, Stephen D

    2015-04-23

    Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing. Genetically guided anatomical mapping revealed that these neurons densely innervate the lung and send long-range projections to different brainstem targets. Npy2r neurons are largely slow-conducting C fibers, while P2ry1 neurons are largely fast-conducting A fibers that contact pulmonary endocrine cells (neuroepithelial bodies). Optogenetic stimulation of P2ry1 neurons acutely silences respiration, trapping animals in exhalation, while stimulating Npy2r neurons causes rapid, shallow breathing. Activating P2ry1 neurons did not impact heart rate or gastric pressure, other autonomic functions under vagal control. Thus, the vagus nerve contains intermingled sensory neurons constituting genetically definable labeled lines with different anatomical connections and physiological roles. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Gut chemosensing: interactions between gut endocrine cells and visceral afferents.

    Science.gov (United States)

    Raybould, Helen E

    2010-02-16

    Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on a new data on endocrine cells in chemosensing in the GI tract, in particular on new findings on glucose-sensing by gut EEC cells and the importance of incretin peptides and vagal afferents in glucose homeostasis, on the role of G protein coupled receptors in gut chemosensing, and on the possibility that gut endocrine cells may be involved in the detection of a luminal constituent other than nutrients, the microbiota. The role of vagal afferent pathways as a downstream target of EEC cell products will be considered and, in particular, exciting new data on the plasticity of the vagal afferent pathway with respect to expression of receptors for GI hormones and how this may play a role in energy homeostasis will also be discussed. Copyright 2009 Elsevier B.V. All rights reserved.

  4. Vasopressin content in the cerebrospinal fluid and fluid perfusing cerebral ventricles in rats after the afferent vagus nerve fibres stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    Experiments were carried out on male rats in urethane anaesthesia. Cerebroventricular system was perfused with McIlwain-Rodniht`s solution from lateral ventricles to cerebellomedullary cistern. Both vagus nerves were cut and the central ends of the nerves were electrically stimulated during the collection of the third 30-min portion of perfusing fluid. Vasopressin (AVP) was determined by radioimmunoassay in samples of the cerebrospinal fluid (CSF) (the first portion) and in five successive samples of the perfusing fluid. AVP concentration in the CSF was several times greater than in the fluid perfusing cerebral ventricles. Alternate electrical stimulation of both vagus nerves did not change considerably the release of AVP into the fluid perfusing the cerebral ventricles in rat, although a certain upward tendency could be observed. It seems that only AVP raised in circulating blood and not in CSF, after vagus nerves stimulation may act on the central nervous structures. (author). 37 refs, 3 figs, 1 tab.

  5. Is intuitive eating related to resting state vagal activity?

    Science.gov (United States)

    Peschel, Stephanie K V; Tylka, Tracy L; Williams, DeWayne P; Kaess, Michael; Thayer, Julian F; Koenig, Julian

    2017-11-15

    Efferent and afferent fibers of the vagus nerve are involved in regulating hunger and satiety. Vagally-mediated heart rate variability (vmHRV) reflects vagal activity. Previously no study addressed a potential association between resting state vagal activity and intuitive eating. Self-reports on intuitive eating and measures of resting state vmHRV were obtained in 39 students (16 female, mean age: 19.64±1.44years). Hierarchical multiple regression models showed that, after controlling for gender, age, and body mass index, resting vagal activity was inversely related to the Unconditional Permission to Eat subscale of the Intuitive Eating scale. Individuals with higher resting vagal activity tend to be less willing to eat desired foods and are more likely to label certain foods as forbidden. Future studies should include measures of self-regulation and eating disorder symptomatology to identify potential mediators or moderators when attempting to replicate these preliminary findings in larger samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. [Stimulation of gastric mucosa afferents by phenylephrine potentiates anticonvulsive and eliminates sedative action of sodium valproate in the pentylenetetrazol kindling model in rats].

    Science.gov (United States)

    Serdiuk, S E; Gmiro, V E; Veselkina, O S

    2014-01-01

    Sodium valproate after chronic intragastric administration in the high dose of 100-200 mg/kg eliminates generalized clonic-tonic pentylenetetrazol seizures in 100 % of rats, but only in 33-57 % of rats it prevents local clonic kindling seizures. Strong sedation is induced by the specified doses of sodium valproate. The combined oral chronic administration of phenylephrine in threshold, noneffective alone dose of 0.2 mg/kg and sodium valproate in high doses of 100 mg/kg and 200 mg/kg potentiates anticonvulsive action of sodium valproate, because prevents both clonic-tonic kindling. seizures in 100 % of rats and clonic kindling seizures in 86-100 % of rats, and also it increases in 1.7-1.9 times anticonvulsive activity of valproate. The specified combinations of sodium valproate with phenylephrine do not produce the sedative side effect. The basis of the mechanism of potentiation of anticonvulsive action and elimination of sedative action of sodium valproate in high doses is the stimulation of gastric mucosa afferents by phenylephrine.

  7. Gut Chemosensing: Interactions between Gut Endocrine Cells and Visceral Afferents

    OpenAIRE

    Raybould, Helen E.

    2009-01-01

    Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on new data on endocrine cells in chemosensing in the GI tract, in particular on new fi...

  8. Upper gastrointestinal dysmotility after spinal cord injury: Is diminished vagal sensory processing one culprit?

    Directory of Open Access Journals (Sweden)

    Gregory M Holmes

    2012-07-01

    Full Text Available Despite the widely recognized prevalence of gastric, colonic and anorectal dysfunction after SCI, significant knowledge gaps persist regarding the mechanisms leading to post-SCI gastrointestinal (GI impairments. Briefly, the regulation of GI function is governed by a mix of parasympathetic, sympathetic and enteric neurocircuitry. Unlike the intestines, the stomach is dominated by parasympathetic (vagal control whereby gastric sensory information is transmitted via the afferent vagus nerve to neurons of the nucleus tractus solitarius (NTS. The NTS integrates this sensory information with signals from throughout the CNS. Glutamatergic and GABAergic NTS neurons project to other nuclei, including the preganglionic parasympathetic neurons of the dorsal motor nucleus of the vagus (DMV. Finally, axons from the DMV project to gastric myenteric neurons, again, through the efferent vagus nerve. SCI interrupts descending input to the lumbosacral spinal cord neurons that modulate colonic motility and evacuation reflexes. In contrast, vagal neurocircuitry remains anatomically intact after injury. This review presents evidence that unlike the post-SCI loss of supraspinal control which leads to colonic and anorectal dysfunction, gastric dysmotility occurs as an indirect or secondary pathology following SCI. Specifically, emerging data points toward diminished sensitivity of vagal afferents to GI neuroactive peptides, neurotransmitters and, possibly, macronutrients. The neurophysiological properties of rat vagal afferent neurons are highly plastic and can be altered by injury or energy balance. A reduction of vagal afferent signaling to NTS neurons may ultimately bias NTS output toward unregulated GABAergic transmission onto gastric-projecting DMV neurons. The resulting gastroinhibitory signal may be one mechanism leading to upper GI dysmotility following SCI.

  9. Protection against Ischemia-Induced Oxidative Stress Conferred by Vagal Stimulation in the Rat Heart: Involvement of the AMPK-PKC Pathway

    Directory of Open Access Journals (Sweden)

    Wei-Jin Zang

    2012-11-01

    Full Text Available Reactive oxygen species (ROS production is an important mechanism in myocardial ischemia and nicotinamide adenine dinucleotide phosphate (NADPH oxidase is one of major sources of ROS in the heart. Previous studies showed that vagus nerve stimulation (VNS is beneficial in treating ischemic heart diseases. However, the effect of VNS on ROS production remains elusive. In this study, we investigated the role of VNS onischemia-induced ROS production. Our results demonstrated that VNS alleviated the myocardial injury, attenuated the cardiac dysfunction, reserved the antioxidant enzyme activity and inhibited the formation of ROS as evidenced by the decreased NADPH oxidase (Nox activity and superoxide fluorescence intensity as well as the expression of p67phox, Rac1 and nitrotyrosine. Furthermore, VNS resulted in the phosphorylation and activation of adenosine monophosphate activated protein kinase (AMPK, which in turn led to an inactivation of Nox by protein kinase C (PKC; however, the phenomena were repressed by the administration of a muscarinic antagonist atropine. Taken together, these data indicate that VNS decreases ROS via AMPK-PKC-Nox pathway; this may have potential importance for the treatment of ischemic heart diseases.

  10. Electrical carotid sinus stimulation in treatment resistant arterial hypertension.

    Science.gov (United States)

    Jordan, Jens; Heusser, Karsten; Brinkmann, Julia; Tank, Jens

    2012-12-24

    Treatment resistant arterial hypertension is commonly defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. The sympathetic nervous system promotes arterial hypertension and cardiovascular as well as renal damage, thus, providing a logical treatment target in these patients. Recent physiological studies suggest that baroreflex mechanisms contribute to long-term control of sympathetic activity and blood pressure providing an impetus for the development of electrical carotid sinus stimulators. The concept behind electrical stimulation of baroreceptors or baroreflex afferent nerves is that the stimulus is sensed by the brain as blood pressure increase. Then, baroreflex efferent structures are adjusted to counteract the perceived blood pressure increase. Electrical stimulators directly activating afferent baroreflex nerves were developed years earlier but failed for technical reasons. Recently, a novel implantable device was developed that produces an electrical field stimulation of the carotid sinus wall. Carefully conducted experiments in dogs provided important insight in mechanisms mediating the depressor response to electrical carotid sinus stimulation. Moreover, these studies showed that the treatment success may depend on the underlying pathophysiology of the hypertension. Clinical studies suggest that electrical carotid sinus stimulation attenuates sympathetic activation of vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus lowering blood pressure. Yet, not all patients respond to treatment. Additional clinical trials are required. Patients equipped with an electrical carotid sinus stimulator provide a unique opportunity gaining insight in human baroreflex physiology. Copyright © 2012. Published by Elsevier B.V.

  11. Pulmonary vein region ablation in experimental vagal atrial fibrillation: role of pulmonary veins versus autonomic ganglia.

    Science.gov (United States)

    Lemola, Kristina; Chartier, Denis; Yeh, Yung-Hsin; Dubuc, Marc; Cartier, Raymond; Armour, Andrew; Ting, Michael; Sakabe, Masao; Shiroshita-Takeshita, Akiko; Comtois, Philippe; Nattel, Stanley

    2008-01-29

    Pulmonary vein (PV) -encircling radiofrequency ablation frequently is effective in vagal atrial fibrillation (AF), and there is evidence that PVs may be particularly prone to cholinergically induced arrhythmia mechanisms. However, PV ablation procedures also can affect intracardiac autonomic ganglia. The present study examined the relative role of PVs versus peri-PV autonomic ganglia in an experimental vagal AF model. Cholinergic AF was studied under carbachol infusion in coronary perfused canine left atrial PV preparations in vitro and with cervical vagal stimulation in vivo. Carbachol caused dose-dependent AF promotion in vitro, which was not affected by excision of all PVs. Sustained AF could be induced easily in all dogs during vagal nerve stimulation in vivo both before and after isolation of all PVs with encircling lesions created by a bipolar radiofrequency ablation clamp device. PV elimination had no effect on atrial effective refractory period or its responses to cholinergic stimulation. Autonomic ganglia were identified by bradycardic and/or tachycardic responses to high-frequency subthreshold local stimulation. Ablation of the autonomic ganglia overlying all PV ostia suppressed the effective refractory period-abbreviating and AF-promoting effects of cervical vagal stimulation, whereas ablation of only left- or right-sided PV ostial ganglia failed to suppress AF. Dominant-frequency analysis suggested that the success of ablation in suppressing vagal AF depended on the elimination of high-frequency driver regions. Intact PVs are not needed for maintenance of experimental cholinergic AF. Ablation of the autonomic ganglia at the base of the PVs suppresses vagal responses and may contribute to the effectiveness of PV-directed ablation procedures in vagal AF.

  12. Vagal Blocking for Obesity Control

    DEFF Research Database (Denmark)

    Johannessen, Helene; Revesz, David; Kodama, Yosuke

    2017-01-01

    BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device...

  13. Anti‐inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation

    Science.gov (United States)

    Sinniger, Valérie; Pellissier, Sonia

    2016-01-01

    Abstract Brain and viscera interplay within the autonomic nervous system where the vagus nerve (VN), containing approximately 80% afferent and 20% efferent fibres, plays multiple key roles in the homeostatic regulations of visceral functions. Recent data have suggested the anti‐inflammatory role of the VN. This vagal function is mediated through several pathways, some of them still debated. The first one is the anti‐inflammatory hypothalamic–pituitary–adrenal axis which is stimulated by vagal afferent fibres and leads to the release of cortisol by the adrenal glands. The second one, called the cholinergic anti‐inflammatory pathway, is mediated through vagal efferent fibres that synapse onto enteric neurons which release acetylcholine (ACh) at the synaptic junction with macrophages. ACh binds to α‐7‐nicotinic ACh receptors of those macrophages to inhibit the release of tumour necrosis (TNF)α, a pro‐inflammatory cytokine. The last pathway is the splenic sympathetic anti‐inflammatory pathway, where the VN stimulates the splenic sympathetic nerve. Norepinephrine (noradrenaline) released at the distal end of the splenic nerve links to the β2 adrenergic receptor of splenic lymphocytes that release ACh. Finally, ACh inhibits the release of TNFα by spleen macrophages through α‐7‐nicotinic ACh receptors. Understanding of these pathways is interesting from a therapeutic point of view, since they could be targeted in various ways to stimulate anti‐inflammatory regulation in TNFα‐related diseases such as inflammatory bowel disease and rheumatoid arthritis. Among others, VN stimulation, either as an invasive or non‐invasive procedure, is becoming increasingly frequent and several clinical trials are ongoing to evaluate the potential effectiveness of this therapy to alleviate chronic inflammation. PMID:27059884

  14. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation.

    Science.gov (United States)

    Bonaz, Bruno; Sinniger, Valérie; Pellissier, Sonia

    2016-10-15

    Brain and viscera interplay within the autonomic nervous system where the vagus nerve (VN), containing approximately 80% afferent and 20% efferent fibres, plays multiple key roles in the homeostatic regulations of visceral functions. Recent data have suggested the anti-inflammatory role of the VN. This vagal function is mediated through several pathways, some of them still debated. The first one is the anti-inflammatory hypothalamic-pituitary-adrenal axis which is stimulated by vagal afferent fibres and leads to the release of cortisol by the adrenal glands. The second one, called the cholinergic anti-inflammatory pathway, is mediated through vagal efferent fibres that synapse onto enteric neurons which release acetylcholine (ACh) at the synaptic junction with macrophages. ACh binds to α-7-nicotinic ACh receptors of those macrophages to inhibit the release of tumour necrosis (TNF)α, a pro-inflammatory cytokine. The last pathway is the splenic sympathetic anti-inflammatory pathway, where the VN stimulates the splenic sympathetic nerve. Norepinephrine (noradrenaline) released at the distal end of the splenic nerve links to the β2 adrenergic receptor of splenic lymphocytes that release ACh. Finally, ACh inhibits the release of TNFα by spleen macrophages through α-7-nicotinic ACh receptors. Understanding of these pathways is interesting from a therapeutic point of view, since they could be targeted in various ways to stimulate anti-inflammatory regulation in TNFα-related diseases such as inflammatory bowel disease and rheumatoid arthritis. Among others, VN stimulation, either as an invasive or non-invasive procedure, is becoming increasingly frequent and several clinical trials are ongoing to evaluate the potential effectiveness of this therapy to alleviate chronic inflammation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  15. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

    Science.gov (United States)

    Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

  16. Excitability changes in sacral afferents innervating the urethra, perineum and hindlimb skin of the cat during micturition

    Science.gov (United States)

    Buss, R R; Shefchyk, S J

    1999-01-01

    Excitability changes in afferents innervating the urethra, perineum and hindlimb were measured in decerebrated cats during micturition and in response to stimulation of lumbosacral afferents. Increases in excitability were interpreted as primary afferent depolarization (PAD) and decreases as primary afferent hyperpolarization.Excitability increases were observed in 11 of 19 urethral pudendal afferents during micturition. Four of these 11 afferents showed an excitability increase during voiding. Seven of these showed a biphasic change with a decrease in excitability when sphincter activity resumed at the end of the void. Three of 19 afferents showed an excitability decrease during micturition and no change was detected in five afferents.During micturition, the peak amplitude of urethral afferent-evoked excitatory postsynaptic potentials in seven of eight sphincter motoneurones was diminished to a mean of 36% of control values.Eighty per cent of hindlimb cutaneous afferents and 50% of dorsal penile/clitoral and superficial perineal nerve afferents in the sacral cord showed increased excitability during voiding. No excitability increases were measured in 13 hindlimb cutaneous fibres examined in the lumbar segments.PAD was observed in sacral urethral, perineal and hindlimb cutaneous afferents in response to electrical stimulation of other perineal, urethral, hindlimb cutaneous and group II muscle afferents.It is concluded that control of transmission from urethral afferents by the micturition circuitry is different to that by sensory transmission from hindlimb and perineal regions during micturition. We hypothesize that more than one population of sacral PAD-mediating interneurones is involved. PMID:9852338

  17. Cortical vs. afferent stimulation as an adjunct to functional task practice training: a randomized, comparative pilot study in people with cervical spinal cord injury.

    Science.gov (United States)

    Gomes-Osman, Joyce; Field-Fote, Edelle C

    2015-08-01

    To assess single-session effects of three different types of stimuli known to increase cortical excitability when combined with functional task practice. Randomized cross-over trial. A total of 24 participants with chronic cervical spinal cord injury. One 30-minute session of each, applied concurrently with functional task practice: transcranial direct current stimulation, vibration, and transcutaneous electrical nerve stimulation. Nine-hole Peg Test, pinch force, visuomotor tracking, and cortical excitability were collected at pretest, posttest and late posttest (30 minutes after). Early effects (posttest minus pretest) and short-term persistence (late posttest minus pretest) were assessed using a general linear mixed model. Magnitude of effect size was assessed using the Cohen's d. Transcutaneous electrical nerve stimulation was associated with moderate, significant early effects and short-term persistence on Nine-hole Peg Test performance (1.8 ±1.8, p = 0.003, d = 0.59; 2.0 ±2.5, p stimulation (1.8 ±2.5, p = 0.003, Cohen's d = 0.52) was also associated with significant short-term persistence of moderate size on Nine-hole Peg Test performance (1.8 ±2.5, p = 0.003, Cohen's d = 0.52) and visuomotor tracking performance (p = 0.05, d = 0.51). Early effects on corticomotor excitability were significant for transcutaneous electrical nerve stimulation (p = 0.003), approached significance for transcranial direct current stimulation (p = 0.07), and only vibration was associated with significant short-term persistence (p = 0.006). Meaningful improvements in aspects of hand-related function that persisted at least 30 minutes after intervention were observed with transcutaneous electrical nerve stimulation and transcranial direct current stimulation, when combined with functional task practice. © The Author(s) 2014.

  18. Dopamine D1/D5, But not D2/D3, Receptor Dependency of Synaptic Plasticity at Hippocampal Mossy Fiber Synapses that Is Enabled by Patterned Afferent Stimulation, or Spatial Learning.

    Science.gov (United States)

    Hagena, Hardy; Manahan-Vaughan, Denise

    2016-01-01

    Although the mossy fiber (MF) synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24 h) synaptic plasticity that is akin to that observed at the Schaffer collateral (SCH)-CA1 and perforant path (PP)-dentate gyrus (DG) synapses of freely behaving rats. In addition, they also respond to novel spatial learning with very enduring forms of long-term potentiation (LTP) and long-term depression (LTD). These latter forms of synaptic plasticity are directly related to the learning behavior: novel exploration of generalized changes in space facilitates the expression of LTP at MF-CA3 synapses, whereas exploration of novel configurations of large environmental features facilitates the expression of LTD. In the absence of spatial novelty, synaptic plasticity is not expressed. Motivation is a potent determinant of whether learning about the spatial experience effectively occurs and the neuromodulator dopamine (DA) plays a key role in motivation-based learning. Prior research on the regulation by DA receptors of long-term synaptic plasticity in CA1 and DG synapses in vivo suggests that whereas D2/D3 receptors may modulate a general predisposition toward expressing plasticity, D1/D5 receptors may directly regulate the direction of change in synaptic strength that occurs during learning. Although the CA3 region is believed to play a pivotal role in many forms of learning, the role of dopamine receptors in persistent (>24 h) forms of synaptic plasticity at MF-CA3 synapses is unknown. Here, we report that whereas pharmacological antagonism of D2/D3 receptors had no impact on LTP or LTD, antagonism of D1/D5 receptors significantly impaired LTP and LTD that were induced by solely by means of patterned afferent stimulation, or LTP/LTD that are typically enhanced by the conjunction of afferent stimulation and novel spatial learning. These data indicate an

  19. Functional electrical stimulation post-spinal cord injury improves locomotion and increases afferent input into the central nervous system in rats.

    Science.gov (United States)

    Beaumont, Eric; Guevara, Edgar; Dubeau, Simon; Lesage, Frederic; Nagai, Mary; Popovic, Milos

    2014-01-01

    Functional electrical stimulation (FES) has been found to be effective in restoring voluntary functions after spinal cord injury (SCI) and stroke. However, the central nervous system (CNS) changes that occur in as a result of this therapy are largely unknown. To examine the effects of FES on the restoration of voluntary locomotor function of the CNS in a SCI rat model. SCI rats were instrumented with chronic FES electrodes in the hindlimb muscles and were divided into two groups: (a) FES therapy and (b) sedentary. At day 7 post-SCI, the animals were assessed for locomotion performance by using a Basso, Beattie and Bresnahan (BBB) scale. They were then anesthetized for a terminal in vivo experiment. The lumbar spinal cord and somatosensory cortex were exposed and the instrumented muscles were stimulated electrically. Associated neurovascular responses in the CNS were recorded with an intrinsic optical imaging system. FES greatly improved locomotion recovery by day 7 post-SCI, as measured by BBB scores (P spinal cord and somatosensory cortex when the muscles were stimulated between 1 and 3 motor threshold (MT). Hind limb rehabilitation with FES is an effective strategy to improve locomotion during the acute phase post-SCI. The results of this study indicate that after FES, the CNS preserves/acquires the capacity to respond to peripheral electrical stimulation.

  20. Muscle afferent excitability testing in spinal root-intact rats: dissociating peripheral afferent and efferent volleys generated by intraspinal microstimulation.

    Science.gov (United States)

    Tomatsu, Saeka; Kim, Geehee; Confais, Joachim; Seki, Kazuhiko

    2017-02-01

    Presynaptic inhibition of the sensory input from the periphery to the spinal cord can be evaluated directly by intra-axonal recording of primary afferent depolarization (PAD) or indirectly by intraspinal microstimulation (excitability testing). Excitability testing is superior for use in normal behaving animals, because this methodology bypasses the technically challenging intra-axonal recording. However, use of excitability testing on the muscle or joint afferent in intact animals presents its own technical challenges. Because these afferents, in many cases, are mixed with motor axons in the peripheral nervous system, it is crucial to dissociate antidromic volleys in the primary afferents from orthodromic volleys in the motor axon, both of which are evoked by intraspinal microstimulation. We have demonstrated in rats that application of a paired stimulation protocol with a short interstimulus interval (ISI) successfully dissociated the antidromic volley in the nerve innervating the medial gastrocnemius muscle. By using a 2-ms ISI, the amplitude of the volleys evoked by the second stimulation was decreased in dorsal root-sectioned rats, but the amplitude did not change or was slightly increased in ventral root-sectioned rats. Excitability testing in rats with intact spinal roots indicated that the putative antidromic volleys exhibited dominant primary afferent depolarization, which was reasonably induced from the more dorsal side of the spinal cord. We concluded that excitability testing with a paired-pulse protocol can be used for studying presynaptic inhibition of somatosensory afferents in animals with intact spinal roots.NEW & NOTEWORTHY Excitability testing of primary afferents has been used to evaluate presynaptic modulation of synaptic transmission in experiments conducted in vivo. However, to apply this method to muscle afferents of animals with intact spinal roots, it is crucial to dissociate antidromic and orthodromic volleys induced by spinal

  1. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    Full Text Available Physiological high frequency activities (HFA are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections, or different terminal layers (layer IV vs. layer II/III affect its frequency, we, in the primary somatosensory cortex (SI, compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response and N80 (late response of somatosensory evoked potentials (HFA(SEP(N20 and HFA(SEP(N80 and compared those overriding N1 and N2 (first and second responses of cortico-cortical evoked potentials (HFA(CCEP(N1 and HFA(CCEP(N2. HFA(SEP(N20 showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1 had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1 and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

  2. Optimization of Transcutaneous Vagus Nerve Stimulation Using Functional MRI.

    Science.gov (United States)

    Yakunina, Natalia; Kim, Sam Soo; Nam, Eui-Cheol

    2017-04-01

    Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy, depression, and a number of other disorders. Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) has been considered as a non-invasive alternative. Several functional magnetic resonance imaging (fMRI) studies on the effects of tVNS used different stimulation parameters and locations in the ear, which makes it difficult to determine the optimal tVNS methodology. The present study used fMRI to determine the most effective location for tVNS. Four stimulation locations in the ear were compared: the inner tragus, inferoposterior wall of the ear canal, cymba conchae, and earlobe (sham). Thirty-seven healthy subjects underwent two 6-min tVNS stimulation runs per electrode location (monophasic rectangular 500 μs pulses, 25 Hz). General linear model was performed using SPM; region-of-interest analyses were performed for the brainstem areas. Stimulation at the ear canal resulted in the weakest activation of the nucleus of solitary tract (NTS), the recipient of most afferent vagal projections, and of the locus coeruleus (LC), a brainstem nucleus that receives direct input from the NTS. Stimulation of the inner tragus and cymba conchae activated these two nuclei as compared to sham. However, ROI analysis showed that only stimulation of the cymba conchae produced a significantly stronger activation in both the NTS and LC than did the sham stimulation. These findings suggest that tVNS at the cymba conchae properly activates the vagal pathway and results in its strongest activation, and thus may be the optimal location for tVNS therapies applied to the auricle. © 2016 International Neuromodulation Society.

  3. Effect of ozone on breathing in dogs: vagal and nonvagal mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, K.; Nadel, J.A.; Hahn, H.L.

    1987-01-01

    We exposed two awake dogs with a chronic tracheostomy and the cervical vagus nerves exteriorized in skin loops to 1.0 ppm of ozone (O/sub 3/) for 2 h at intervals of 4 wk. We measured ventilatory variables before and after O/sub 3/ exposure during rest and exercise before and after vagal block. We compared the effects of vagal blockade, exercise, and O/sub 3/ on the primary determinants of breathing pattern (VT/TI, VT/TE, TI, and TE) in each of three conditions: base line (steady state), during hypercapnia, and after inhalation of 1% histamine. Under base-line conditions, O/sub 3/ increased respiratory rate and decreased tidal volume (VT) by shortening time of expiration (TE) and time of inspiration (TI) without affecting VT/TI, an indicator of the neural drive to breathing. During progressive hypercapnia, O/sub 3/ shortened TE and TI by effects both on tonic (nonvolume-related) and on phasic (volume-related) vagal inputs, and only the latter were prevented completely by cooling of the vagus nerves. Histamine-induced tachypnea was increased by O/sub 3/ and was totally blocked by cooling the vagus nerves. It was concluded that O/sub 3/ shortens the timing of respiration without increasing ventilatory drive, shortens TI and TE through vagal and nonvagal pathways, increases tonic nonvagal and phasic vagal inputs, and stimulates more than one vagal fiber type.

  4. Musings on the wanderer: what's new in our understanding of vago-vagal reflexes? III. Activity-dependent plasticity in vago-vagal reflexes controlling the stomach.

    Science.gov (United States)

    Travagli, R Alberto; Hermann, Gerlinda E; Browning, Kirsteen N; Rogers, Richard C

    2003-02-01

    Vago-vagal reflex circuits modulate digestive functions from the oral cavity to the transverse colon. Previous articles in this series have described events at the level of the sensory receptors encoding the peripheral stimuli, the transmission of information in the afferent vagus, and the conversion of this data within the dorsal vagal complex (DVC) to impulses in the preganglionic efferents. The control by vagal efferents of the postganglionic neurons impinging on the glands and smooth muscles of the target organs has also been illustrated. Here we focus on some of the mechanisms by which these apparently static reflex circuits can be made quite plastic as a consequence of the action of modulatory inputs from other central nervous system sources. A large body of evidence has shown that the neuronal elements that constitute these brain stem circuits have nonuniform properties and function differently according to status of their target organs and the level of activity in critical modulatory inputs. We propose that DVC circuits undergo a certain amount of short-term plasticity that allows the brain stem neuronal elements to act in harmony with neural systems that control behavioral and physiological homeostasis.

  5. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity

    DEFF Research Database (Denmark)

    Frøkjaer, J B; Bergmann, S; Brock, C

    2016-01-01

    , using transcutaneous electrical vagal nerve stimulation (t-VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy subjects. METHODS: Eighteen healthy subjects were randomized to a subject-blinded, sham......-controlled, cross-over study with an active protocol including stimulation of auricular branch of the vagus nerve, and breathing at full inspiratory capacity and forced full expiration. Recording of cardiac derived parameters including cardiac vagal tone, moderate pain thresholds to muscle, and bone pressure......BACKGROUND: The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori-motor function. Our research question was to whether combined electrical and physiological modulation of vagal tone...

  6. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish.

    Science.gov (United States)

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander; Liao, James C

    2015-01-15

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. Copyright © 2015 the American Physiological Society.

  7. Vagal withdrawal during endoscopic retrograde cholangiopancreatography

    DEFF Research Database (Denmark)

    Christensen, M; Rasmussen, Verner; Schulze, S

    2000-01-01

    tone during the ERCP was found, but we observed no difference between the metoprolol and the placebo group. For both groups the lowest vagal tone occurred at maximum heart rate during endoscopy. The SDRR/meanRR ratio returned towards base line for the subsequent 60 min after endoscopy. CONCLUSIONS....... During ERCP the patients were monitored with a Holter tape recorder. Holter tapes from 31 patients (16 receiving metoprolol) were available to analyse the ratio of the standard deviations of the RR intervals (SDRR) to the mean RR intervals (measure of vagal tone) during ERCP. RESULTS: A decreased vagal...

  8. Vagal modulation of pre-inspiratory activity in hypoglossal discharge in the decerebrate rat.

    Science.gov (United States)

    Ghali, Michael George Zaki

    2015-08-15

    Respiration consists of three phases--inspiration (I), post-inspiration (post-I), and late expiration (E2). Pre-I is a subphase occurring at the end of E2. Hypoglossal (XII) discharge contains I and occasionally pre-I activity. Functionally, XII pre-I underlies tongue muscle contraction and expansion of the upper airway, causing a decrease in airway resistance in anticipation of the succeeding inspiratory effort. It has been shown that vagotomy causes an increase in pre-I activity in XII in anesthetized animals. Also, in anesthetized artificially-ventilated animals, XII onset is synchronized with that of inspiratory phrenic nerve (PhN) activity. Therefore, we sought to systematically test the hypothesis that XII pre-I is present in vagus-intact unanesthetized decerebrate animals and vagal afferents negatively modulate XII pre-I discharge in decerebrate rats, in the absence of confounding anesthesia. Experiments were performed on seven Sprague-Dawley unanesthetized decerebrate adult male rats and bilateral PhN and XII recordings performed. In three animals, vagotomy was performed during PhN recordings and one animal was vagotomized during initial surgical preparation prior to recordings. In vagus-intact animals, XII pre-I duration averaged 12.4 ms. Vagotomy was associated with greater XII pre-I duration, expressed in absolute time (89.5 vs. 12.4 ms; pdecerebrate animals and is negatively modulated by vagal afferents. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Activation and inhibition of the micturition reflex by penile afferents in the cat

    National Research Council Canada - National Science Library

    John P. Woock; Paul B. Yoo; Warren M. Grill

    2008-01-01

    .... We quantified the effects on the micturition reflex of sensory inputs from genital afferents traveling in the penile component of the somatic pudendal nerve by electrical stimulation of the dorsal nerve of the penis (DNP) in α...

  10. Activation and inhibition of the micturition reflex by penile afferents in the cat

    OpenAIRE

    Woock, John P; Yoo, Paul B.; Grill, Warren M.

    2008-01-01

    Coordination of the urinary bladder and the external urethral sphincter (EUS) is controlled by descending projections from the pons, and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents, traveling in the penile component of the somatic pudendal nerve, by electrical stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized male cats. Depending on the frequency of stimulation ...

  11. Vagally mediated inhibition of acoustic stress-induced cortisol release by orally administered kappa-opioid substances in dogs.

    Science.gov (United States)

    Bueno, L; Gue, M; Fargeas, M J; Alvinerie, M; Junien, J L; Fioramonti, J

    1989-04-01

    The effects of oral vs. iv administration of kappa- and mu-opioid agonists on plasma cortisol release induced by acoustic stress (AS) were evaluated in fasted dogs with an implanted jugular catheter. AS was induced by 1 h of music (less than or equal to 86 decibels) played through earphones and was accompanied by a 382% maximal rise in plasma cortisol after 15-30 min. Administered orally 30 min before the AS session, both U-50488 (0.1 mg/kg) and PD 117-302 (0.05 mg/kg) significantly (P less than or equal to 0.01) decreased (by 71.2% and 80.9%, respectively) the maximal increase in plasma cortisol induced by AS, while bremazocine, morphine, as well as iv administration of U-50488 at similar doses were ineffective. The effects of U-50488 and PD 117-302 orally administered (0.1 mg/kg) on the hypercortisolemia induced by AS were abolished by pretreatment with iv naloxone (0.1 mg/kg) or MR 2266 (0.1 mg/kg). Naloxone given alone significantly (P less than 0.01) increased basal plasma cortisol, without affecting cortisol increase induced by AS. Vagotomy abolished the effects of orally administered U-50488 on the AS-induced increase in plasma cortisol. Neither U-50488 nor PD 117302 (0.1 mg/kg, orally) reduced the increase in plasma cortisol induced by intracerebroventricular administration of ovine CRF (100 ng/kg). It is concluded that kappa- but not mu-opioid agonists are able to inhibit the stimulation of the hypothalamo-pituitary-adrenocortical axis induced by AS by acting selectively on peripheral kappa-receptors located in the wall of the proximal gut. This action is neurally mediated through afferent vagal fibers affecting central nervous system release of CRF induced by a centrally acting stressor.

  12. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    Science.gov (United States)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  13. Duodenal lipid sensing activates vagal afferents to regulate non-shivering brown fat thermogenesis in rats.

    Directory of Open Access Journals (Sweden)

    Clémence Blouet

    Full Text Available Previous evidence indicates that duodenal lipid sensing engages gut-brain neurocircuits to determine food intake and hepatic glucose production, but a potential role for gut-brain communication in the control of energy expenditure remains to be determined. Here, we tested the hypothesis that duodenal lipid sensing activates a gut-brain-brown adipose tissue neuraxis to regulate thermogenesis. We demonstrate that direct administration of lipids into the duodenum increases brown fat temperature. Co-infusion of the local anesthetic tetracaine with duodenal lipids abolished the lipid-induced increase in brown fat temperature. Systemic administration of the CCKA receptor antagonist devazepide blocked the ability of duodenal lipids to increase brown fat thermogenesis. Parenchymal administration of the N-methyl-d-aspartate receptor blocker MK-801 directly into the caudomedial nucleus of the solitary tract also abolished duodenal lipid-induced activation of brown fat thermogenesis. These findings establish that duodenal lipid sensing activates a gut-brain-brown fat axis to determine brown fat temperature, and thereby reveal a previously unappreciated pathway that regulates thermogenesis.

  14. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

    Science.gov (United States)

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2014-10-01

    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals. Copyright © 2014 the American Physiological Society.

  15. Anatomy and Physiology of Phrenic Afferent Neurons.

    Science.gov (United States)

    Nair, Jayakrishnan; Streeter, Kristi A; Turner, Sara M F; Sunshine, Michael D; Bolser, Donald C; Fox, Emily J; Davenport, Paul W; Fuller, David D

    2017-08-23

    Large diameter myelinated phrenic afferents discharge in phase with diaphragm contraction and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that 1) activation of both myelinated and non-myelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; 2) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; 3) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and 4) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and non-myelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity. Copyright © 2017, Journal of Neurophysiology.

  16. Vagal sensory evoked potentials disappear under the neuromuscular block - an experimental study.

    Science.gov (United States)

    Leutzow, Bianca; Lange, Jörn; Gibb, Andreas; Schroeder, Henry; Nowak, Andreas; Wendt, Michael; Usichenko, Taras I

    2013-09-01

    Transcutaneous vagal nerve stimulation is a promising treatment modality in patients suffering mood disorders and chronic pain, however, the mechanisms are still to be elucidated. A recently developed technique of EEG responses to electrical stimulation of the inner side of the tragus suggests that these responses are far field potentials, generated in the vagal system - Vagal Sensory Evoked Potentials (VSEP). To reproduce the VSEP technique free from myogenic artifacts. Fourteen ASA I-II patients scheduled for elective surgery in standardized Total Intravenous Anesthesia (TIVA) were enrolled. Transcutaneous electrical stimulation was applied to the inner side of the right tragus. Averaged EEG responses were recorded from the electrode positions C4-F4 and T4-O2 before and after induction of TIVA, during the maximal effect of the non-depolarizing muscle relaxing agent, cis-atracurium (C-AR) and after recovery from C-AR under TIVA. Typical response curves with P1, N1 and P2 peaks could be reproduced in all patients before and after anesthesia induction. The response curves disappeared during the C-AR action and re-appeared after recovery from C-AR under TIVA. The disappearance of the scalp responses to electrical tragus stimulation under the neuromuscular block suggests a muscular origin of these potentials. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Immunomodulation of afferent neurons in guinea-pig isolated airway.

    Science.gov (United States)

    Riccio, M M; Myers, A C; Undem, B J

    1996-01-01

    duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent nerve terminals projecting from the airway and thus may contribute to the pathophysiology of allergic airway diseases. PMID:8866873

  18. Ventral tegmental area afferents and drug-dependent behaviors

    Directory of Open Access Journals (Sweden)

    Idaira eOliva

    2016-03-01

    Full Text Available Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA, a midbrain structure comprised of dopamine, GABA and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects of drugs. In this review we present evidence implicating the VTA in drug-related behaviors, highlight the diversity of neuronal populations in the VTA, and discuss the behavioral effects of selectively manipulating VTA afferents. Future experiments are needed to determine which VTA afferents and what neuronal populations in the VTA mediate specific drug-dependent behaviors. Further studies are also necessary for identifying the afferent-specific synaptic alterations onto dopamine and non-dopamine neurons in the VTA following drug administration. The identification of neural circuits and adaptations involved with drug-dependent behaviors can highlight potential neural targets for pharmacological and deep brain stimulation interventions to treat substance abuse disorders.

  19. Role of brainstem TRH/TRH-R1 receptors in the vagal gastric cholinergic response to various stimuli including sham-feeding.

    Science.gov (United States)

    Taché, Y; Yang, H; Miampamba, M; Martinez, V; Yuan, P Q

    2006-04-30

    Pavlov's pioneering work established that sham-feeding induced by sight or smell of food or feeding in dogs with permanent esophagostomy stimulates gastric acid secretion through vagal pathways. Brain circuitries and transmitters involved in the central vagal regulation of gastric function have recently been unraveled. Neurons in the dorsal vagal complex including the dorsal motor nucleus of the vagus (DMN) express thyrotropin-releasing hormone (TRH) receptor and are innervated by TRH fibers originating from TRH synthesizing neurons in the raphe pallidus, raphe obscurus and the parapyramidal regions. TRH injected into the DMN or cisterna magna increases the firing of DMN neurons and gastric vagal efferent discharge, activates cholinergic neurons in gastric submucosal and myenteric plexuses, and induces a vagal-dependent, atropine-sensitive stimulation of gastric secretory (acid, pepsin) and motor functions. TRH antibody or TRH-R1 receptor oligodeoxynucleotide antisense pretreatment in the cisterna magna or DMN abolished vagal-dependent gastric secretory and motor responses to sham-feeding, 2-deoxy-D-glucose, cold exposure and chemical activation of cell bodies in medullary raphe nuclei. TRH excitatory action in the DMN is potentiated by co-released prepro-TRH-(160-169) flanking peptide, Ps4 and 5-HT, and inhibited by a number of peptides involved in the stress/immune response and inhibition of food-intake. These neuroanatomical, electrophysiological and neuropharmacological data are consistent with a physiological role of brainstem TRH in the central vagal stimulation of gastric myenteric cholinergic neurons in response to several vagal dependent stimuli including sham-feeding.

  20. Voltage-gated sodium channels in nociceptive versus non-nociceptive nodose vagal sensory neurons innervating guinea pig lungs

    Science.gov (United States)

    Kwong, Kevin; Carr, Michael J; Gibbard, Anna; Savage, Tony J; Singh, Kuljit; Jing, Junping; Meeker, Sonya; Undem, Bradley J

    2008-01-01

    Lung vagal sensory fibres are broadly categorized as C fibres (nociceptors) and A fibres (non-nociceptive; rapidly and slowly adapting low-threshold stretch receptors). These afferent fibre types differ in degree of myelination, conduction velocity, neuropeptide content, sensitivity to chemical and mechanical stimuli, as well as evoked reflex responses. Recent studies in nociceptive fibres of the somatosensory system indicated that the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels (VGSC) are preferentially expressed in the nociceptive fibres of the somatosensory system (dorsal root ganglia). Whereas TTX-R sodium currents have been documented in lung vagal sensory nerves fibres, a rigorous comparison of their expression in nociceptive versus non-nociceptive vagal sensory neurons has not been carried out. Using multiple approaches including patch clamp electrophysiology, immunohistochemistry, and single-cell gene expression analysis in the guinea pig, we obtained data supporting the hypothesis that the TTX-R sodium currents are similarly distributed between nodose ganglion A-fibres and C-fibres innervating the lung. Moreover, mRNA and immunoreactivity for the TTX-R VGSC molecules NaV1.8 and NaV1.9 were present in nearly all neurons. We conclude that contrary to findings in the somatosensory neurons, TTX-R VGSCs are not preferentially expressed in the nociceptive C-fibre population innervating the lungs. PMID:18187475

  1. Chicken (Gallus domesticus) inner ear afferents.

    Science.gov (United States)

    Hara, H; Chen, X; Hartsfield, J F; Hara, J; Martin, D; Fermin, C D

    1998-01-01

    Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

  2. Nitric oxide has tonic inhibitory effect, but is not involved in the vagal control or VIP effects on motility of the porcine antrum

    DEFF Research Database (Denmark)

    Schmidt, P T; Orskov, C; Rasmussen, T N

    2003-01-01

    BACKGROUND: The involvement of nitric oxide (NO) in vagal control and vasoactive intestinal polypeptide (VIP)-induced effects on antral motility was studied using isolated perfused preparations of porcine gastric antrum with intact vagal innervation. METHODS: The presence of NO and VIP-producing ......BACKGROUND: The involvement of nitric oxide (NO) in vagal control and vasoactive intestinal polypeptide (VIP)-induced effects on antral motility was studied using isolated perfused preparations of porcine gastric antrum with intact vagal innervation. METHODS: The presence of NO and VIP......-producing neurons was studied using immunohistochemistry and histochemical techniques. Widespread, but not total, co-localization of NO and VIP immunoreactivity was found in the submucosa and in the muscle layers. RESULTS: Electrical stimulation of the vagus nerves for 5 min (8 Hz, 10 mA, 4 msec) increased...

  3. Spontaneous Contractions Evoke Afferent Nerve Firing in Mouse Bladders With Detrusor Overactivity

    Science.gov (United States)

    McCarthy, Carly J.; Zabbarova, Irina V.; Brumovsky, Pablo R.; Roppolo, James R.; Gebhart, Gerald F.; Kanai, Anthony J.

    2010-01-01

    Purpose Afferent nerve firing has been linked to spontaneous bladder contractions in a number of lower urinary tract pathologies and it may lead to urgency and incontinence. Using optical mapping, single unit recording and tension measurements we investigated the correlation between afferent nerve firing and spontaneous bladder contractions in spinal cord transected mice. Materials and Methods Bladder-nerve preparations (bladder sheets and the associated L6-S2 pelvic nerves) were dissected from normal and spinal cord transected mice showing overactivity on cystometry and opened along the ventral aspect from base to dome. Bladder sheets were mounted horizontally in a temperature regulated chamber to simultaneously record Ca2+ transients across the mucosal surface, single unit afferent nerve firing and whole bladder tension. Results Single unit afferent fibers were identified by probing their receptive fields. Fibers showed a graded response to von Frey stimulation and a frequency of afferent firing that increased as a function of the degree of stretch. Optical maps of Ca2+ transients in control bladders demonstrated multiple initiation sites that resulted in high frequency, low amplitude spontaneous contractions. Alternatively in maps of the bladders of spinal cord transected mice Ca2+ transients arose from 1 or 2 focal sites, resulting in low frequency, high amplitude contractions and concomitant afferent firing. Conclusions Large amplitude, spontaneous bladder contractions evoke afferent nerve activity, which may contribute to incontinence. PMID:19157431

  4. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Science.gov (United States)

    Hagbom, Marie; Istrate, Claudia; Engblom, David; Karlsson, Thommie; Rodriguez-Diaz, Jesus; Buesa, Javier; Taylor, John A; Loitto, Vesa-Matti; Magnusson, Karl-Eric; Ahlman, Håkan; Lundgren, Ove; Svensson, Lennart

    2011-07-01

    Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.

  5. Rotavirus stimulates release of serotonin (5-HT from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Directory of Open Access Journals (Sweden)

    Marie Hagbom

    2011-07-01

    Full Text Available Rotavirus (RV is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT by enterochromaffin (EC cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1 and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃, but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.

  6. Resting Vagal Tone and Vagal Response to Stress: Associations with Anxiety, Aggression and Perceived Anxiety Control among Youth

    OpenAIRE

    Scott, Brandon G.; Weems, Carl F.

    2014-01-01

    This study tested the associations of both resting vagal tone and vagal response to stress with anxiety control beliefs, anxiety, and aggression among 80 youth (aged 11-17 years). Measures included physiological assessments of emotion regulation along with youth self-report of anxiety control beliefs, anxiety, and aggression and caregiver reports of their child's anxiety and aggression. Resting vagal tone was positively related to anxiety control beliefs, but negatively associated with anxiet...

  7. Activation and inhibition of the micturition reflex by penile afferents in the cat.

    Science.gov (United States)

    Woock, John P; Yoo, Paul B; Grill, Warren M

    2008-06-01

    Coordination of the urinary bladder and the external urethral sphincter is controlled by descending projections from the pons and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents traveling in the penile component of the somatic pudendal nerve by electrical stimulation of the dorsal nerve of the penis (DNP) in alpha-chloralose anesthetized male cats. Depending on the frequency of stimulation (range, 1-40 Hz), activation of penile afferents either inhibited contractions of the bladder and promoted urine storage or activated the bladder and produced micturition. Stimulation of the DNP at 5-10 Hz inhibited distension-evoked contractions and increased the maximum bladder capacity before incontinence. Conversely, stimulation at 33 and 40 Hz augmented distension-evoked contractions. When the bladder was filled above a threshold volume (70% of the volume necessary for distension-evoked contractions), stimulation at 20-40 Hz activated de novo the micturition reflex and elicited detrusor contractions that increased voiding efficiency compared with distension-evoked voiding. Electrical stimulation of the DNP with a cuff electrode or percutaneous wire electrode produced similar results. The ability to evoke detrusor contractions by activation of the DNP was preserved following acute spinal cord transection. These results demonstrate a clear role of genital afferents in modulating the micturition reflex and suggest the DNP as a potential target for functional restoration of bladder control using electrical stimulation.

  8. An indirect component in the evoked compound action potential of the vagal nerve

    Science.gov (United States)

    Ordelman, Simone C. M. A.; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P. J.; Veltink, Peter H.

    2010-12-01

    The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

  9. Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

    Science.gov (United States)

    Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

    2017-01-01

    Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

  10. Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

    Science.gov (United States)

    Sen, Tanusree; Cawthon, Carolina R; Ihde, Benjamin Thomas; Hajnal, Andras; DiLorenzo, Patricia M; de La Serre, Claire B; Czaja, Krzysztof

    2017-05-01

    /HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation. © 2016.

  11. Vagal function in health and disease: Studies in Pittsburgh.

    NARCIS (Netherlands)

    Gianaros, P.J.; Graham, R.; Somsen, R.J.M.; van der Molen, M.W.; Jennings, J.R.

    2002-01-01

    The integration of behavioral processes with changes in vagally-controlled heart rate has been the focus of our investigations. A series of studies is reviewed showing that central and peripheral response inhibition is a primary source of transient, vagally-induced cardiac slowing during information

  12. Moderate Baseline Vagal Tone Predicts Greater Prosociality in Children

    Science.gov (United States)

    Miller, Jonas G.; Kahle, Sarah; Hastings, Paul D.

    2017-01-01

    Vagal tone is widely believed to be an important physiological aspect of emotion regulation and associated positive behaviors. However, there is inconsistent evidence for relations between children's baseline vagal tone and their helpful or prosocial responses to others (Hastings & Miller, 2014). Recent work in adults suggests a quadratic…

  13. TRH/TRH-R1 receptor signaling in the brain medulla as a pathway of vagally mediated gut responses during the cephalic phase.

    Science.gov (United States)

    Taché, Yvette; Adelson, David; Yang, Hong

    2014-01-01

    Pavlov's seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the cephalic phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response

  14. Afferent Endocrine Control of Eating

    DEFF Research Database (Denmark)

    Langhans, Wolfgang; Holst, Jens Juul

    2016-01-01

    The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

  15. Temperature differentially facilitates spontaneous but not evoked glutamate release from cranial visceral primary afferents.

    Directory of Open Access Journals (Sweden)

    Jessica A Fawley

    Full Text Available Temperature is fundamentally important to all biological functions including synaptic glutamate release. Vagal afferents from the solitary tract (ST synapse on second order neurons in the nucleus of the solitary tract, and glutamate release at this first central synapse controls autonomic reflex function. Expression of the temperature-sensitive Transient Receptor Potential Vanilloid Type 1 receptor separates ST afferents into C-fibers (TRPV1+ and A-fibers (TRPV1-. Action potential-evoked glutamate release is similar between C- and A-fiber afferents, but TRPV1 expression facilitates a second form of synaptic glutamate release in C-fibers by promoting substantially more spontaneous glutamate release. The influence of temperature on different forms of glutamate release is not well understood. Here we tested how temperature impacts the generation of evoked and spontaneous release of glutamate and its relation to TRPV1 expression. In horizontal brainstem slices of rats, activation of ST primary afferents generated synchronous evoked glutamate release (ST-eEPSCs at constant latency whose amplitude reflects the probability of evoked glutamate release. The frequency of spontaneous EPSCs in these same neurons measured the probability of spontaneous glutamate release. We measured both forms of glutamate from each neuron during ramp changes in bath temperature of 4-5 °C. Spontaneous glutamate release from TRPV1+ closely tracked with these thermal changes indicating changes in the probability of spontaneous glutamate release. In the same neurons, temperature changed axon conduction registered as latency shifts but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These data indicate that TRPV1-operated glutamate release is independent of action potential-evoked glutamate release in the same neurons. Together, these support the hypothesis that evoked and spontaneous glutamate release originate from two pools of vesicles that are

  16. Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel disease.

    Science.gov (United States)

    Bonaz, B; Sinniger, V; Pellissier, S

    2017-07-01

    Inflammatory bowel disease (IBD), that is Crohn's disease (CD) and ulcerative colitis, affects about 1.5 million persons in the USA and 2.2 million in Europe. The pathophysiology of IBD involves immunological, genetic and environmental factors. The treatment is medico-surgical but suspensive. Anti-TNFα agents have revolutionized the treatment of IBD but have side effects. In addition, a non-negligible percentage of patients with IBD stop or take episodically their treatment. Consequently, a nondrug therapy targeting TNFα through a physiological pathway, devoid of major side effects and with a good cost-effectiveness ratio, would be of interest. The vagus nerve has dual anti-inflammatory properties through its afferent (i.e. hypothalamic-pituitary-adrenal axis) and efferent (i.e. the anti-TNFα effect of the cholinergic anti-inflammatory pathway) fibres. We have shown that there is an inverse relationship between vagal tone and plasma TNFα level in patients with CD, and have reported, for the first time, that chronic vagus nerve stimulation has anti-inflammatory properties in a rat model of colitis and in a pilot study performed in seven patients with moderate CD. Two of these patients failed to improve after 3 months of vagus nerve stimulation but five were in deep remission (clinical, biological and endoscopic) at 6 months of follow-up and vagal tone was restored. No major side effects were observed. Thus, vagus nerve stimulation provides a new therapeutic option in the treatment of CD. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  17. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  18. Afferent-specific AMPA receptor subunit composition and regulation of synaptic plasticity in midbrain dopamine neurons by abused drugs

    OpenAIRE

    Good, Cameron H.; Lupica, Carl R.

    2010-01-01

    Ventral tegmental area (VTA) dopamine (DA) neurons play a pivotal role in processing reward-related information and are involved in drug addiction and mental illness in humans. Information is conveyed to the VTA in large part by glutamatergic afferents that arise in various brain nuclei, including the pedunculopontine nucleus (PPN). Using a unique rat brain slice preparation, we found that PPN stimulation activates afferents targeting GluR2-containing AMPA receptors (AMPAR) on VTA DA neurons,...

  19. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  20. Daith Piercing in a Case of Chronic Migraine: A Possible Vagal Modulation

    Directory of Open Access Journals (Sweden)

    Angelo Cascio Rizzo

    2017-11-01

    Full Text Available Daith piercing is an ear piercing located at the crus of the helix, bilaterally. It is getting great consent on social media as alternative treatment in chronic migraine. No data about its efficacy and action are available in scientific literature so far. We present the case of a 54-year-old male patient suffering from refractory chronic migraine with medication-overuse, who substantially improved after bilateral ear daith piercing. His migraine was refractory to symptomatic as well as prophylactic therapies. He used to treat headaches with up to five symptomatic drugs per attack and had attempted several pharmacological preventive therapies, including Onabotulinumtoxin A. He also underwent detoxification treatments with intravenous steroids and diazepam, without durable benefit. At the time of daith piercing, the headache-related disability measures showed a HIT-6 score of 64, a MIDAS-score of 70, and a 11-point Box scale of 5. On his own free will, he decided to get a “daith piercing.” After that, he experienced a reduction of migraine attacks, which became very rare, and infrequent, less disabling episodes of tension-type headache (HIT-6 score of 56; MIDAS score of 27, 11-point Box scale of 3. Painkiller assumption has much decreased: he takes only one tablet of indomethacin 50 mg to treat tensive headaches, about four times per month. Beyond a placebo effect, we can speculate a vagal modulation as the action mechanism of daith piercing: a nociceptive sensory stimulus applied to trigeminal and vagal areas of the ear can activate ear vagal afferents, which can modulate pain pathways by means of projections to the caudal trigeminal nucleus, to the locus coeruleus and to the nucleus raphe magnus. Currently, daith piercing cannot be recommended as migraine treatment because of the lack of scientific evidence, the unquantified rate of failure and the associated risks with insertion. However, given the increasing but anecdotal evidence, we

  1. Sensitization of group III and IV muscle afferents in mouse after ischemia and reperfusion injury

    Science.gov (United States)

    Ross, Jessica L.; Queme, Luis F.; Shank, Aaron T.; Hudgins, Renita C.; Jankowski, Michael P.

    2014-01-01

    Ischemic myalgia is a unique type of muscle pain in the patient population. The role that discrete muscle afferent subpopulations play in the generation of pain during ischemic events, however, has yet to be determined. Using two brachial artery occlusion models to compare prolonged ischemia or transient ischemia with reperfusion of the muscles, we found that both injuries caused behavioral decrements in grip strength, as well as increased spontaneous pain behaviors. Using our ex vivo forepaw muscles, median and ulnar nerves, dorsal root ganglion (DRG), and spinal cord recording preparation, we found after both prolonged and transient ischemia, that there was a significant increase in the number of afferents that responded to both noxious and non-noxious36 chemical (lactate, ATP, varying pH) stimulation of the muscles compared to uninjured controls. However, we found an increase in firing to heat stimuli specifically in muscle afferents during prolonged ischemia, but a distinct increase in afferent firing to non-noxious chemicals and decreased mechanical thresholds after transient ischemia. The unique changes in afferent function observed also corresponded with distinct patterns of gene expression in the DRGs. Thus the development of ischemic myalgia may be generated by unique afferent based mechanisms during prolonged and transient ischemia. Perspective This study analyzes the response properties of thinly myelinated group III and unmyelinated group IV muscle afferents during prolonged and transient ischemia in addition to pain behaviors and alterations in DRG gene expression in mouse. Results suggest that mechanisms of pain generation during prolonged ischemia may be different from ischemia/reperfusion. PMID:25245401

  2. Role of Connexin40 in the autoregulatory response of the afferent arteriole

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Giese, Isaiah; Braunstein, Thomas Hartig

    2012-01-01

    in the regulation of renin secretion. We investigated the effect of deleting the Cx40 gene on autoregulation of afferent arteriolar diameter in response to acute changes in renal perfusion pressure. The experiments were performed using the isolated blood perfused juxtamedullary nephron preparation in kidneys...... obtained from wild type or Cx40 knockout mice. Renal perfusion pressure was increased in steps from 75 mm Hg to 155 mm Hg and the response in afferent arteriolar diameter was measured. Hereafter a papillectomy was performed to inhibit TGF and the pressure steps were repeated. Conduction of intercellular Ca......(2+) changes in response to local electrical stimulation was examined in isolated interlobular arteries and afferent arterioles from wild type or Cx40 knockout mice. Cx40 knockout mice had an impaired autoregulatory response to acute changes in renal perfusion pressure compared to wild type mice...

  3. Adrenergic receptors and gastric secretion in dogs. Is a "tonic balance" relationship between vagal and beta 2-adrenergic activity a possibility?

    DEFF Research Database (Denmark)

    Gottrup, F; Hovendal, C; Bech, K

    1984-01-01

    The relative influence of adrenergic receptors on gastric acid secretion in the dog stomach with different vagal activity or "tone" is almost unknown. beta-adrenoceptors seem to be most important for the direct effect of adrenergic stimulation on acid secretion. In this study the effects...... of vagotomy and beta 2-adrenoceptor activity were studied in conscious gastric fistula dogs. Pentagastrin stimulated acid output was increased slightly in non-vagotomized dogs and to its prevagotomy level in vagotomized dogs after propranolol infusion. Practolol showed no such effect. Histamine stimulated...... acid secretion was not influenced significantly by beta-blockade. Similar dose-response curves were found for non-vagotomized dogs with high beta 2-adrenergic tone and dogs with low vagal tone (vagotomy) after pentagastrin and histamine stimulated acid secretion. This study indicates...

  4. Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs.

    Science.gov (United States)

    Diaz, V; Arsenault, J; Praud, J P

    2000-11-01

    The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO(2) rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.

  5. Tuning afferent synapses of hippocampal interneurons by neuropeptide Y

    DEFF Research Database (Denmark)

    Ledri, Marco; Sørensen, Andreas Toft; Erdelyi, Ferenc

    2011-01-01

    extrahippocampal afferents. Various excitatory and inhibitory afferent and efferent synapses of the hippocampal CCK basket cells express serotoninergic, cholinergic, cannabinoid, and benzodiazepine sensitive receptors, all contributing to their functional plasticity. We explored whether CCK basket cells...

  6. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

    Science.gov (United States)

    Crowley, Olga V.; Kimhy, David; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Lachman, Margie E.; Tun, Patricia A.; Ryff, Carol D.; Seeman, Teresa E.; Sloan, Richard P.

    2015-01-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  7. The role of genital nerve afferents in the physiology of the sexual response and pelvic floor function.

    Science.gov (United States)

    Tajkarimi, Kambiz; Burnett, Arthur L

    2011-05-01

    Our understanding of genital and pelvic floor physiology is rapidly expanding. Penile erection is a neurovascular event controlled by spinal autonomic centers, the activity of which is dependent on input from supraspinal centers and the genitalia. Genital afferent stimulation excites spinal autonomic nuclei and supraspinal sexual centers of both genders. To present a detailed understanding of the functional importance of genital afferent neuroanatomy and neurophysiology.   English-written articles of diverse disciplines from 1980 to 2010 that contained information on genital anatomy, pudendal/dorsal/perineal/cavernous nerves, vibratory stimulation, reflexogenic erection, peripheral/central nervous system-mediated erectile and micturition pathways, and sexual arousal in animals and humans were reviewed. Analysis of supporting evidence for the role of genital afferents in the physiology of erectile response and pelvic floor function. Basic science and clinical studies support the concept that pudendal nerve circuitry serves an essential purpose for sexual behavior, erectile function, penile rigidity, ejaculation, and micturition. Males and females share a comparable pattern of genital afferent neuroanatomy and neurophysiology, and sexual and micturition reflexes are similar in both genders. Pudendal nerve branches communicate with the cavernous nerves and are nitric oxide synthase positive. Genital afferents activate multiple spinal reflexes that modulate erection and micturition. Genital sensory information is transmitted to supraspinal centers important for sexual function.   There is expanding support for the critical role of genital afferent neurophysiology in the mechanisms of erectile function and micturition. Genital afferent stimulation is a safe and natural modality that can be harnessed to amplify autonomic and somatic activity within the penis, female genitalia, spinal cord, and higher centers via established neurological principles. Such physiological

  8. Transcutaneous Vagus Nerve Stimulation: A Promising Method for Treatment of Autism Spectrum Disorders

    Science.gov (United States)

    Jin, Yu; Kong, Jian

    2017-01-01

    Transcutaneous Vagus Nerve Stimulation (tVNS) on the auricular branch of the vagus nerve has been receiving attention due to its therapeutic potential for neuropsychiatric disorders. Although the mechanism of tVNS is not yet completely understood, studies have demonstrated the potential role of vagal afferent nerve stimulation in the regulation of mood and visceral state associated with social communication. In addition, a growing body of evidence shows that tVNS can activate the brain regions associated with Autism Spectrum Disorder (ASD), trigger neuroimmune modulation and produce treatment effects for comorbid disorders of ASD such as epilepsy and depression. We thus hypothesize that tVNS may be a promising treatment for ASD, not only for comorbid epilepsy and depression, but also for the core symptoms of ASD. The goal of this manuscript is to summarize the findings and rationales for applying tVNS to treat ASD and propose potential parameters for tVNS treatment of ASD. PMID:28163670

  9. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    Science.gov (United States)

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

    1998-01-01

    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  10. Firing of antagonist small-diameter muscle afferents reduces voluntary activation and torque of elbow flexors.

    Science.gov (United States)

    Kennedy, David S; McNeil, Chris J; Gandevia, Simon C; Taylor, Janet L

    2013-07-15

    During muscle fatigue, firing of small-diameter muscle afferents can decrease voluntary activation of the fatigued muscle. However, these afferents may have a more widespread effect on other muscles in the exercising limb. We examined if the firing of fatigue-sensitive afferents from elbow extensor muscles in the same arm reduces torque production and voluntary activation of elbow flexors. In nine subjects we examined voluntary activation of elbow flexors by measuring changes in superimposed twitches evoked by transcranial magnetic stimulation of the motor cortex during brief (2-3 s) maximal voluntary contractions (MVC). Inflation of a blood pressure cuff following a 2-min sustained MVC blocked blood flow to the fatigued muscle and maintained firing of small-diameter afferents. After a fatiguing elbow flexion contraction, maximal flexion torque was lower (26.0 ± 4.4% versus 67.9 ± 5.2% of initial maximal torque; means ± s.d.; P torque was also reduced (82.2 ± 4.9% versus 91.4 ± 2.3% of initial maximal torque; P = 0.007), superimposed twitches were larger (2.7 ± 0.7% versus 1.3 ± 0.2% ongoing MVC; P = 0.02) and voluntary activation lower (81.6 ± 8.2% versus 95.5 ± 6.9%; P = 0.04) with than without ischaemia. After a fatiguing contraction, voluntary drive to the fatigued muscles is reduced with continued input from small-diameter muscle afferents. Furthermore, fatigue of the elbow extensor muscles decreases voluntary drive to unfatigued elbow flexors of the same arm. Therefore, firing of small-diameter muscle afferents from one muscle can affect voluntary activation and hence torque generation of another muscle in the same limb.

  11. Convergence of ipsi- and contralateral muscle afferents on common interneurons mediating reciprocal inhibition of ankle plantarflexors in humans

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Geertsen, Svend S.; Stevenson, Andrew James Thomas

    2017-01-01

    Recent studies have shown that afferents arising from muscle receptors located on one side can affect the activity of muscles on the contralateral side. In animal preparations, evidence supports that afferent pathways originating from one limb converge onto interneurons mediating disynaptic...... reciprocal Ia inhibition of the opposite limb. This study was designed to investigate whether this pathway is similar in humans to that described in animals. Thirteen healthy volunteers participated in one of two experiments. In experiment 1, the effects of ipsilateral posterior tibial nerve (i...... induced a significantly greater inhibition compared to their separate effects. These data provide evidence of convergence on common inhibitory interneurons by muscle afferents activated by iPTN and cCPN stimulation during sitting. Since the inhibition elicited by cCPN stimulation is known to be mediated...

  12. pH-evoked dural afferent signaling is mediated by ASIC3 and is sensitized by mast cell mediators.

    Science.gov (United States)

    Yan, Jin; Wei, Xiaomei; Bischoff, Christina; Edelmayer, Rebecca M; Dussor, Gregory

    2013-09-01

    Prior studies have shown that decreased meningeal pH activates dural afferents via opening of acid-sensing ion channels (ASICs), suggesting one pathophysiological mechanism for the generation of headaches. The studies described here further examined the ASIC subtype mediating pH-induced dural-afferent activation and examined whether sensitization influences pH responses. Given the potential importance of meningeal mast cells to headache, the goal of this study was to evaluate dural afferent responses to pH following sensitization with mast cell mediators. Cutaneous allodynia was measured in rats following stimulation of the dura with decreased pH alone or in combination with mast cell mediators. Trigeminal ganglion neurons retrogradely labeled from the dura were stained with an ASIC3 antibody using immunohistochemistry. Current and action potentials evoked by changes in pH alone or in combination with mast cell mediators were measured in retrogradely labeled dural afferents using patch-clamp electrophysiology. pH-sensitive dural afferents generated currents in response to the ASIC3 activator 2-guanidine-4-methylquinazoline (GMQ), approximately 80% of these neurons express ASIC3 protein, and pH-evoked behavioral responses were inhibited by the ASIC3 blocker APETx2. Following exposure to mast cell mediators, dural afferents exhibited increased pH-evoked excitability, and cutaneous allodynia was observed at higher pH than with pH stimuli alone. These data indicate that the predominant ASIC subtype responding to decreased meningeal pH is ASIC3. Additionally, they demonstrate that in the presence of inflammation, dural afferents respond to even smaller decreases in pH providing further support for the ability of small pH changes within the meninges to initiate afferent input leading to headache. © 2013 American Headache Society.

  13. [Is the afferent auditory message modulated by the cortex?].

    Science.gov (United States)

    de Lavernhe-Lemaire, M C; Robier, A

    1997-12-01

    An eventual modulation of the afferent auditory message by the cortex is the subject of this study. To test this hypothesis, clicks (10 Hz, 100 microseconds) of white noise of 40 and 70 dB Hl were sent alternatively into the ears of normally hearing volunteers, while the brainstem evoked potentials were recorded. The subjects were asked to focus or relax their attention on one or other ear. Thirty subjects aged less than 25 years (15 men and 15 women) with normal hearing level, were split into two groups. The first group was asked to focus first on the more strongly stimulated ear (70 dB), the second group on the more weakly stimulated one (40 dB). Each subject received (1) without any instruction about attention: 40 dB on the left ear (L), 70 dB on the right ear (R); 40 dB then 70 dB bilateral; (2) 2 runs with 40 dB on the L and 70 dB on the R focussing on the most or less strongly stimulated ear; (3) a run without instruction with 70 dB on the L and 40 dB on the R, and (4) two runs with 70 dB on the L and 40 dB on the R focussing enough on the more or less strongly stimulated ear. On the evoked potentials simultaneously recorded, amplitudes and latencies of the pikes were measured and compared. From these experiments, the following elements were obtained. (1) The measured potentials were always caused by ipsilateral stimuli. (2) Focussing on left or right ear was not equivalent. (3) A gender difference appeared in the brainstem auditory responses. (4) Preferential attention paid to the left ear was more efficient than to the right one. (5) Attention can alter the whole nervous pathway with considerable lengthening of O-I, O-III, O-V, III-V, I-V but not I-III latencies. The III wave amplitude generally decreased on the side where attention was focussed while V waves seemed not to vary. These first results indicate that a cortico-efferent pathway stimulated by the attention plays a role in the auditory responses modifying the afferent message. These effects were

  14. Malignant Transformation of Vagal Nerve Schwannoma in to ...

    African Journals Online (AJOL)

    Vagal schwannomas are benign, rare peripheral nerve sheath tumors in the head and neck region. Some physicians opt to closely observe cases of schwannoma of the neck on an outpatient basis rather than to perform radical surgery. However, there is a possibility, albeit rare, of malignant transformation of a.

  15. Thrombolytic therapy preserves vagal activity early after acute myocardial infarction

    DEFF Research Database (Denmark)

    Lind, P; Hintze, U; Møller, M

    2001-01-01

    OBJECTIVE: The purpose of this study was to evaluate the effects of thrombolytic therapy on vagal tone after acute myocardial infarction (AMI). DESIGN: Holter monitoring for 24 h was performed at hospital discharge and 6 weeks after AMI in 74 consecutive male survivors of a first AMI, who fulfilled...

  16. Malignant Transformation of Vagal Nerve Schwannoma in to ...

    African Journals Online (AJOL)

    Here, we are reporting the first case from the Indian subcontinent which was transformed into the angiosarcoma from benign vagal schwannoma over a long period. A 47‑year‑old male patient complaining of left sided neck swelling since last 12 years, swelling was insidious in onset, gradually progressive very slowly. In last ...

  17. Can natural ways to stimulate the vagus nerve improve seizure control?

    Science.gov (United States)

    Yuen, Alan W C; Sander, Josemir W

    2017-02-01

    The vagus nerve (VN) is the longest cranial nerve, innervating the neck, thorax and abdomen, with afferent fibers transmitting a range of interoceptive stimuli and efferent fibres to somatic structures and autonomic preganglions. Over the last few decades, electrical stimulation of the VN using implanted devices (VNS) has been developed leading to its approval for the treatment of epilepsy and depression. More recently, non-invasive devices to stimulation the VN have been developed. The VN has many functions and the activity that is most amenable to assessment is its effect in controlling the cardiac rhythm. This can be easily assessed by measuring heart rate variability (HRV). Decreased HRV is a result of poorer vagal parasympathetic tone and is associated with a wide range of ill health conditions including a higher risk of early mortality. People with epilepsy, particularly those with poorly controlled seizures, have been shown to have impaired parasympathetic tone. So, might natural ways to stimulate the VN, shown to improve parasympathetic tone as indicated by increased HRV, improve seizure control? There are numerous natural ways that have been shown to stimulate the VN, improving HRV and hence parasympathetic tone. These natural ways fall mainly into 3 categories - stress reduction, exercise, and nutrition. Though the natural ways to stimulate the VN have been shown to increase HRV, they have not been shown to reduce seizures. The exception is listening to Mozart's music, which has been shown to increase parasympathetic tone and decrease seizures. Clearly much more work is required to examine the effect of the various ways to increase HRV on seizure occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Afferent and efferent activity control in the design of brain computer interfaces for motor rehabilitation.

    Science.gov (United States)

    Cho, Woosang; Vidaurre, Carmen; Hoffmann, Ulrich; Birbaumer, Niels; Ramos-Murguialday, Ander

    2011-01-01

    Stroke is a cardiovascular accident within the brain resulting in motor and sensory impairment in most of the survivors. A stroke can produce complete paralysis of the limb although sensory abilities are normally preserved. Functional electrical stimulation (FES), robotics and brain computer interfaces (BCIs) have been used to induce motor rehabilitation. In this work we measured the brain activity of healthy volunteers using electroencephalography (EEG) during FES, passive movements, active movements, motor imagery of the hand and resting to compare afferent and efferent brain signals produced during these motor related activities and to define possible features for an online FES-BCI. In the conditions in which the hand was moved we limited the movement range in order to control the afferent flow. Although we observed that there is a subject dependent frequency and spatial distribution of efferent and afferent signals, common patterns between conditions and subjects were present mainly in the low beta frequency range. When averaging all the subjects together the most significant frequency bin comparing each condition versus rest was exactly the same for all conditions but motor imagery. These results suggest that to implement an on-line FES-BCI, afferent brain signals resulting from FES have to be filtered and time-frequency-spatial features need to be used.

  19. Synaptic transmission of baro- and chemoreceptors afferents in the NTS second order neurons.

    Science.gov (United States)

    Accorsi-Mendonça, Daniela; Machado, Benedito H

    2013-04-01

    Second order neurons in the nucleus tractus solitarius (NTS) process and integrate the afferent information from arterial baroreceptors with high fidelity and precise timing synaptic transmission. Since 2nd-order NTS neurons receiving baroreceptors inputs are relatively well characterized, their electrophysiological profile has been accepted as a general characteristic for all 2nd-order NTS neurons involved with the processing of different sensorial inputs. On the other hand, the synaptic properties of other afferent systems in NTS, such as the peripheral chemoreceptors, are not yet well understood. In this context, in previous studies we demonstrated that in response to repetitive afferents stimulation, the chemoreceptors 2nd-order NTS neurons also presented high fidelity of synaptic transmission, but with a large variability in the latency of evoked responses. This finding is different in relation to the precise timing transmission for baroreceptor 2nd-order NTS neurons, which was accepted as a general characteristic profile for all 2nd order neurons in the NTS. In this brief review we discuss this new concept as an index of complexity of the sensorial inputs to NTS with focus on the synaptic processing of baro- and chemoreceptor afferents. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Pain processing by spinal microcircuits: afferent combinatorics.

    Science.gov (United States)

    Prescott, Steven A; Ratté, Stéphanie

    2012-08-01

    Pain, itch, heat, cold, and touch represent different percepts arising from somatosensory input. How stimuli give rise to these percepts has been debated for over a century. Recent work supports the view that primary afferents are highly specialized to transduce and encode specific stimulus modalities. However, cross-modal interactions (e.g. inhibition or exacerbation of pain by touch) support convergence rather than specificity in central circuits. We outline how peripheral specialization together with central convergence could enable spinal microcircuits to combine inputs from distinctly specialized, co-activated afferents and to modulate the output signals thus formed through computations like normalization. These issues will be discussed alongside recent advances in our understanding of microcircuitry in the superficial dorsal horn. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Effects of ankle extensor muscle afferent inputs on hip abductor and adductor activity in the decerebrate walking cat.

    Science.gov (United States)

    Bolton, D A E; Misiaszek, J E

    2012-12-01

    Electrical stimulation of the lateral gastrocnemius-soleus (LGS) nerve at group I afferent strength leads to adaptations in the amplitude and timing of extensor muscle activity during walking in the decerebrate cat. Such afferent feedback in the stance leg might result from a delay in stance onset of the opposite leg. Concomitant adaptations in hip abductor and adductor activity would then be expected to maintain lateral stability and balance until the opposite leg is able to support the body. As many hip abductors and adductors are also hip extensors, we hypothesized that stimulation of the LGS nerve at group I afferent strength would produce increased activation and prolonged burst duration in hip abductor and adductor muscles in the premammillary decerebrate walking cat. LGS nerve stimulation during the extensor phase of the locomotor cycle consistently increased burst amplitude of the gluteus medius and adductor femoris muscles, but not pectineus or gracilis. In addition, LGS stimulation prolonged the burst duration of both gluteus medius and adductor femoris. Unexpectedly, long-duration LGS stimulus trains resulted in two distinct outcomes on the hip abductor and adductor bursting pattern: 1) a change of burst duration and timing similar to medial gastrocnemius; or 2) to continue rhythmically bursting uninterrupted. These results indicate that activation of muscle afferents from ankle extensors contributes to the regulation of activity of some hip abductor and adductor muscles, but not all. These results have implications for understanding the neural control of stability during locomotion, as well as the organization of spinal locomotor networks.

  2. Bilateral sensory deprivation of trigeminal afferent fibers on corticomotor control of human tongue musculature: A preliminary study

    DEFF Research Database (Denmark)

    Kothari, Mohit; Baad-Hansen, Lene; Svensson, Peter

    2016-01-01

    Background: Transcranial magnetic stimulation (TMS) has demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs. Objective: The aim of the present study was to determine whether bilateral local anaesthesia (LA) of the lingual...

  3. Constitutive overexpression of muscarinic receptors leads to vagal hyperreactivity.

    Directory of Open Access Journals (Sweden)

    Angelo Livolsi

    Full Text Available BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS. Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2 and M(3 receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2 receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2 receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2 receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits. This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2 receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that

  4. Afferents originating from the dorsal penile nerve excite oxytocin cells in the hypothalamic paraventricular nucleus of the rat.

    Science.gov (United States)

    Yanagimoto, M; Honda, K; Goto, Y; Negoro, H

    1996-09-16

    Electrical stimulation of the dorsal penile nerve (DPN) produced orthodromic excitation in about half of oxytocin cells in the paraventricular nucleus (PVN). In contrast, less than 10% of vasopressin cells were excited. Tactile stimulation of the glans penis by a paintbrush produced excitation in 40% of oxytocin cells. Castration did not prevent activation of oxytocin cells. These results suggest that somatosensory information from the penis is transmitted to the PVN through the DPN and that such afferent input preferentially innervates oxytocin cells.

  5. Afferent diversity and the organization of central vestibular pathways.

    Science.gov (United States)

    Goldberg, J M

    2000-02-01

    This review considers whether the vestibular system includes separate populations of sensory axons innervating individual organs and giving rise to distinct central pathways. There is a variability in the discharge properties of afferents supplying each organ. Discharge regularity provides a marker for this diversity since fibers which differ in this way also differ in many other properties. Postspike recovery of excitability determines the discharge regularity of an afferent and its sensitivity to depolarizing inputs. Sensitivity is small in regularly discharging afferents and large in irregularly discharging afferents. The enhanced sensitivity of irregular fibers explains their larger responses to sensory inputs, to efferent activation, and to externally applied galvanic currents, but not their distinctive response dynamics. Morphophysiological studies show that regular and irregular afferents innervate overlapping regions of the vestibular nuclei. Intracellular recordings of EPSPs reveal that some secondary vestibular neurons receive a restricted input from regular or irregular afferents, but that most such neurons receive a mixed input from both kinds of afferents. Anodal currents delivered to the labyrinth can result in a selective and reversible silencing of irregular afferents. Such a functional ablation can provide estimates of the relative contributions of regular and irregular inputs to a central neuron's discharge. From such estimates it is concluded that secondary neurons need not resemble their afferent inputs in discharge regularity or response dynamics. Several suggestions are made as to the potentially distinctive contributions made by regular and irregular afferents: (1) Reflecting their response dynamics, regular and irregular afferents could compensate for differences in the dynamic loads of various reflexes or of individual reflexes in different parts of their frequency range; (2) The gating of irregular inputs to secondary VOR neurons could

  6. Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

    Science.gov (United States)

    Gladden, M H; Matsuzaki, H

    2002-01-01

    Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents. PMID:12181298

  7. The Effect of Sham Feeding on Neurocardiac Regulation in Healthy Human Volunteers

    Directory of Open Access Journals (Sweden)

    Markad V Kamath

    2007-01-01

    Full Text Available BACKGROUND: Distension and electrical stimuli in the esophagus alter heart rate variability (HRV consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific.

  8. Comparison of assessment methods of cardiac vagal modulation.

    Science.gov (United States)

    Paiva, Vagner Clayton de; Santana, Kelen Rabelo; Silva, Bruno Moreira; Ramos, Plínio Santos; Lovisi, Júlio César Moraes; Araújo, Claudio Gil Soares de; Ricardo, Djalma Rabelo

    2011-12-01

    Several methods have been used to assess cardiac vagal modulation, but there are gaps regarding the association and accuracy of these methods. To investigate the association between three valid, reproducible and commonly methods used to assess cardiac vagal modulation and compare their accuracies. Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced design by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced order by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). Healthy subjects had higher vagal modulation by the three methods (p RSA, but there was no correlation between the T4s and the other two methods. In the group with coronary artery disease, there was a correlation between the results of HRV (pNN50, SDNN, RMSSD, HF ms² and HF n.u.) and RSA. In addition, there was a correlation between the RSA and T4s. Finally, the T4s and RSA methods presented more accurate effect size and better accuracy (p RSA generated partially redundant results in healthy subjects and in patients with coronary artery disease, while the T4s generated results that were complementary to HRV and RSA in healthy subjects. In addition, RSA and T4s methods were more accurate when discriminating cardiac vagal modulation between healthy subjects and patients with coronary artery disease, when compared to HRV.

  9. Deglutition Syncope: Two Case Reports Attributed to Vagal Hyperactivity.

    Science.gov (United States)

    Bhogal, Sukhdeep; Sethi, Pooja; Taha, Yasir; Papireddy, Muralidhar; Mahajan, Akhilesh; Zaidi, Syed Imran M; Ramu, Vijay; Paul, Timir

    2017-01-01

    Deglutition syncope is a relatively rare cause of syncope that belongs to the category of neurally mediated reflex syncopal syndromes. The phenomenon is related to vagal reflex in context to deglutition causing atrioventricular block and acute reduction in cardiac output leading to dizziness or syncope. We present case series of two cases of deglutition syncope, of which first was managed medically and second with pacemaker implantation.

  10. Deglutition Syncope: Two Case Reports Attributed to Vagal Hyperactivity

    OpenAIRE

    Bhogal, Sukhdeep; Sethi, Pooja; Taha, Yasir; Papireddy, Muralidhar; Mahajan, Akhilesh; Zaidi, Syed Imran M.; Ramu, Vijay; Paul, Timir

    2017-01-01

    Deglutition syncope is a relatively rare cause of syncope that belongs to the category of neurally mediated reflex syncopal syndromes. The phenomenon is related to vagal reflex in context to deglutition causing atrioventricular block and acute reduction in cardiac output leading to dizziness or syncope. We present case series of two cases of deglutition syncope, of which first was managed medically and second with pacemaker implantation.

  11. K+ Currents in Isolated Vestibular Afferent Calyx Terminals

    National Research Council Canada - National Science Library

    Dhawan, Ritu; Mann, Scott E; Meredith, Frances L; Rennie, Katherine J

    2010-01-01

    Vestibular hair cells transduce mechanical displacements of their hair bundles into an electrical receptor potential which modulates transmitter release and subsequent action potential firing in afferent neurons...

  12. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  13. Human sinus arrhythmia as an index of vagal cardiac outflow

    Science.gov (United States)

    Eckberg, D. L.

    1983-01-01

    The human central vagal mechanisms were investigated by measuring the intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1000 and 1500 ml) in six young men and women. It was found that as the breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley intervals also increased in proportion to tidal volume, although this influence was small. The phase angles between heart period changes and respiration were found to vary as linear functions of breathing interval. Heart period shortening began in inspiration at short breathing intervals and in expiration at long breathing intervals, while heart period lengthening began in early expiration at all breathing intervals studied. It is concluded that a close relationship exists between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. The results indicate that at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity begin in expiration, progress slowly, and are incompletely expressed at fast breathing ratges.

  14. Rapid shallow breathing evoked by selective stimulation of airway C fibres in dogs.

    Science.gov (United States)

    Coleridge, H M; Coleridge, J C; Roberts, A M

    1983-07-01

    1. We have examined the reflex changes in breathing evoked in anaesthetized dogs by stimulation of the afferent vagal C fibres that supply the intrapulmonary and lower extrapulmonary airways. We stimulated bronchial (intrapulmonary) C fibres selectively by injecting bradykinin into the right bronchial artery (the chest had been opened briefly for insertion of a bronchial arterial catheter).2. Bronchial arterial injection of bradykinin (0.15-1.5 mug in 3-6 sec) usually caused a brief bout of rapid shallow breathing, which was sometimes preceded by apnoea. Infusion of bradykinin (0.2-2.0 mug min(-1) for 2-12 min) caused prolonged rapid shallow breathing, the breathing frequency (f) increasing by 19-102% and tidal volume (V(T)) decreasing by 13-87%; end-tidal P(CO2) decreased by 2-9 mmHg in several experiments. Rapid shallow breathing was also evoked by administration of bradykinin aerosol through a lower tracheal cannula.3. Cutting the vagus nerves or cooling them to 0 degrees C abolished the prolonged rapid shallow breathing evoked by bradykinin, but intermittent disturbances of breathing could still be elicited in some dogs. These residual effects often consisted of irregular spasmodic inspirations, which were abolished by avulsion of the right upper thoracic sympathetic chain.4. Rapid shallow breathing was accompanied by contraction of airway smooth muscle in an innervated segment of the upper trachea; contraction was abolished by cutting or cooling the vagus nerves.5. Arterial blood pressure often decreased briefly when bradykinin was injected into the bronchial artery; changes in pressure were smaller and less frequent when bradykinin was infused slowly, and pressure was usually unaltered when bradykinin was administered as an aerosol. Rapid shallow breathing occurred whether pressure decreased, increased or was unchanged. A number of other observations indicated that the changes in breathing were independent of the changes in blood pressure. Changes in heart

  15. Nonnociceptive afferent activity depresses nocifensive behavior and nociceptive synapses via an endocannabinoid-dependent mechanism.

    Science.gov (United States)

    Yuan, Sharleen; Burrell, Brian D

    2013-12-01

    Previously, low-frequency stimulation (LFS) of a nonnociceptive touch-sensitive neuron has been found to elicit endocannabinoid-dependent long-term depression (eCB-LTD) in nociceptive synapses in the leech central nervous system (CNS) that requires activation of a presynaptic transient receptor potential vanilloid (TRPV)-like receptor by postsynaptically synthesized 2-arachidonoyl glycerol (2-AG). This capacity of nonnociceptive afferent activity to reduce nociceptive signaling resembles gate control of pain, albeit longer lasting in these synaptic experiments. Since eCB-LTD has been observed at a single sensory-motor synapse, this study examines the functional relevance of this mechanism, specifically whether this form of synaptic plasticity has similar effects at the behavioral level in which additional, intersegmental neural circuits are engaged. Experiments were carried out using a semi-intact preparation that permitted both synaptic recordings and monitoring of the leech whole body shortening, a defensive withdrawal reflex that was elicited via intracellular stimulation of a single nociceptive neuron (the N cell). The same LFS of a nonnociceptive afferent that induced eCB-LTD in single synapses also produced an attenuation of the shortening reflex. Similar attenuation of behavior was also observed when 2-AG was applied. LFS-induced behavioral and synaptic depression was blocked by tetrahydrolipstatin (THL), a diacylglycerol lipase inhibitor, and by SB366791, a TRPV1 antagonist. The effects of both THL and SB366791 were observed following either bath application of the drug or intracellular injection into the presynaptic (SB366791) or postsynaptic (THL) neuron. These findings demonstrate a novel, endocannabinoid-based mechanism by which nonnociceptive afferent activity may modulate nocifensive behaviors via action on primary afferent synapses.

  16. Population coding of forelimb joint kinematics by peripheral afferents in monkeys.

    Directory of Open Access Journals (Sweden)

    Tatsuya Umeda

    Full Text Available Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.

  17. Subtypes of muscarinic receptors in vagal inhibitory pathway to the lower esophageal sphincter of the opossum.

    Science.gov (United States)

    Gilbert, R J; Dodds, W J

    1987-10-01

    We assessed the characteristics of muscarinic neural transmission in the vagal inhibitory pathway to the lower esophageal sphincter (LES) of anesthetized opossums. LES relaxation was induced by electrical stimulation of the cervical vagus. Measurements were made of LES relaxation before and after intravenous administration of nicotinic (hexamethonium), serotonergic (5-Meo-DMT), nonselective muscarinic (atropine), and selective muscarinic (pirenzepine-M1 and 4-DAMP-M2) antagonists. The latency of LES relaxation was increased substantially by pirenzepine and atropine, increased slightly by hexamethonium, but was not affected by 4-DAMP or 5-Meo-DMT. Given as concurrent intravenous infusions, hexamethonium, 5-Meo-DMT and 4-DAMP added to pirenzepine or atropine did not significantly increase LES relaxation latency above that caused by pirenzepine or atropine alone. None of the antagonists alone had a significant effect on percent LES relaxation. The combination of pirenzepine or 4-DAMP with hexamethonium and 5-Meo-DMT did not affect percent LES relaxation. The combination of atropine with hexamethonium and 5-Meo-DMT reduced LES relaxation to 18%. The combination of pirenzepine and 4-DAMP with hexamethonium and 5-Meo-DMT, however, had no effect on percent LES relaxation. We conclude that muscarinic participation in vagally induced LES relaxation exhibits two functional receptor subtypes: (1) M1 receptors that determine LES relaxation latency and are antagonized by pirenzepine or atropine, and (2) non-M1, non-M2 receptors (Mx receptors) that contribute to the magnitude of LES relaxation and are antagonized by atropine, but not by pirenzepine or 4-DAMP.

  18. Contribution of vagal pathways to the renal responses to head-out immersion in the nonhuman primate.

    Science.gov (United States)

    Gilmore, J P; Zucker, I H

    1978-02-01

    Studies were carried out to determine the contribution of cardiopulmonary receptors to the renal responses to head-out water immersion in the nonhuman primate. Immersion to the suprasternal notch was associated with significant increases in central venous pressure, urine flow, and sodium excretion. The increased sodium excretion was due primarily to a significant increase in the percent of the filtered sodium excreted. Deoxycorticosterone acetate (DOCA) and antiduretic hormone (ADH) had no substantial effects on these responses. The finding of a vasopressin-resistant hyposthenuria is consistent with the natriuresis of immersion being due, at least in part, to a decrease in sodium reabsorption proximal to the diluting segment, possibly the proximal tubule. Bilateral cervical vagotomy had no substantial influence on the renal responses to immersion, demonstrating that cardiopulmonary receptors whose axons traverse the vagus nerves are not necessary for the homeostatic adjustments to central hypervolemia in the primate. Since the renal and cardiovascular responses of the primate to immersion are essentially the same as those seen in man, it is probable that vagal pathways also are not necessary in man. However, it is possible that sympathetic afferents are involved in the natriuresis observed in the primate during immersion.

  19. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

    Directory of Open Access Journals (Sweden)

    Seol Ah Kim

    Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  20. The influence of contralateral primary afferents on Ia inhibitory interneurones in humans.

    Science.gov (United States)

    Delwaide, P J; Pepin, J L

    1991-01-01

    1. Contralateral influences on short latency reciprocal inhibition between wrist extensor and flexor muscles were investigated in twenty-two healthy volunteers. Reciprocal inhibition, probably mediated through the Ia inhibitory interneurone, was measured by conditioning the flexor carpi radialis (FCR) H reflex by weak stimulation of the ipsilateral radial nerve. Maximum reciprocal inhibition occurring at a precise delay between conditioning and conditioned stimulations was taken as the test level of inhibition. 2. Contralateral median or radial nerves were stimulated at short intervals before the onset of reciprocal inhibition. The latter was increased by 8.6% after median nerve stimulation and decreased by 16.5% after radial nerve stimulation. 3. The contribution of sensory fibres in the two nerves to contralateral effects was investigated by stimulating purely sensory branches of the nerves. No clear modification of the contralateral reciprocal inhibition was observed. The effects produced by mixed nerve stimulation are thus likely to have been mediated by Ia fibres. 4. In three hemiplegic patients where reciprocal inhibition was reduced unilaterally, stimulation on the spastic side produced contralateral effects similar to those observed in normal subjects. This result indicates that contralateral effects are not mediated through the Ia inhibitory interneurone ipsilateral to the conditioning stimulus. 5. Since contralateral effects occur after short delays (2 ms, median nerve; 3 ms, radial nerve), we suggest a functional scheme in which the excitability of Ia inhibitory interneurones is modified by contralateral primary afferents via the interneurones activated by group I fibres, probably Ia fibres. The short delays indicate that the interneurone transmitting primary afferent influences to the contralateral side is probably excitatory. PMID:1895236

  1. The essential role of peripheral respiratory chemoreceptor inputs in maintaining breathing revealed when CO2 stimulation of central chemoreceptors is diminished.

    Science.gov (United States)

    Fiamma, Marie-Noëlle; O'Connor, Edward T; Roy, Arijit; Zuna, Ines; Wilson, Richard J A

    2013-03-15

    Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual-perfused in situ rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas-equilibrated medium. At varying levels of carotid body stimulation (CB PO2/PCO2: 40/60, 100/40, 200/15, 500/15 Torr), we decreased the brainstem perfusate PCO2 in 5 Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40/60), the apnoeic threshold was 3.6 ± 1.4 Torr PCO2 (mean ± SEM, n = 7). Stimulating carotid body afferent activity with either hypercapnia (60 Torr PCO2) or the neuropeptide pituitary adenylate cyclase-activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO2 reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO2.

  2. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

    Science.gov (United States)

    Leung, Felix W

    2008-07-04

    This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

  3. Effect of Microgravity on Afferent Innervation

    Science.gov (United States)

    1998-01-01

    Presentations and publications are: (1) an audiovisual summary web presentation on results from SLM-MIR avian experiments. A color presentation summarizing results from the SLM-MIR and STS-29 avian experiments; (2) color threshold and ratio of S 100B MAP5, NF68/200, GABA and GAD; (3) chicken (Gallus domesticus) inner ear afferents; (4) microgravity in the STS-29 Space Shuttle Discovery affected the vestibular system of chick embryos; (5) expression of S 100B in sensory and secretory cells of the vertebrate inner ear; (6) otoconia biogenesis, phylogeny, composition and functional attributes;(7) the glycan keratin sulfate in inner ear crystals; (8) elliptical-P cells in the avian perilymphatic interface of the tegmentum vasculosum; and (9) LAMP2c and S100B upregulation in brain stem after VIIIth nerve deafferentation.

  4. Critical Airway Compromise due to a Massive Vagal Schwannoma

    LENUS (Irish Health Repository)

    McDermott, AM

    2016-05-01

    We describe the case of a 37-year-old man with a slowly enlarging neck lump and compressive symptoms. He presented to a separate institution 10 years prior where an observational approach was advocated. Following preoperative investigations and embolization, an 11cm vagal schwannoma was excised and vagus nerve was sacrificed. Although conservative management is appropriate for a select patient population, surgical excision is treatment of choice for cervical neurogenic tumours and paraganglionomas and must be considered in young patients or rapidly expanding tumours to avoid compressive symptoms, as in this case.

  5. Vagal activity: effect of age, sex and physical activity pattern.

    Science.gov (United States)

    Araújo, C G; Nobrega, A C; Castro, C L

    1989-01-01

    Heart rate response to a short (4 s) bicycle exercise test during maximal inspiratory apnea was used to assess vagal activity (VA). This study aims to evaluate the role of age, sex and physical activity pattern on VA. A total of 148 subjects, divided into athletes (N = 90) and non-athletes (N = 58) were tested. No correlation was found between age (range from 15 to 42 years) and VA in the male and female athletes (P greater than 0.05). No gender effect could be identified. In spite of a slight tendency toward higher VA in athletes, no significant differences could be found between the two groups.

  6. Lower Cardiac Vagal Tone in Non-Obese Healthy Men with Unfavorable Anthropometric Characteristics

    Science.gov (United States)

    Ramos, Plínio S.; Araújo, Claudio Gil S.

    2010-01-01

    OBJECTIVES: to determine if there are differences in cardiac vagal tone values in non-obese healthy, adult men with and without unfavorable anthropometric characteristics. INTRODUCTION: It is well established that obesity reduces cardiac vagal tone. However, it remains unknown if decreases in cardiac vagal tone can be observed early in non-obese healthy, adult men presenting unfavorable anthropometric characteristics. METHODS: Among 1688 individuals assessed between 2004 and 2008, we selected 118 non-obese (BMI somatotype), a 4-second exercise test to estimate cardiac vagal tone and a maximal cardiopulmonary exercise test to exclude individuals with myocardial ischemia. The same physician performed all procedures. RESULTS: A lower cardiac vagal tone was found for the individuals in the higher quintiles – unfavorable anthropometric characteristics - of BMI (p=0.005), sum of six skinfolds (p=0.037) and waist circumference (p<0.001). In addition, the more endomorphic individuals also presented a lower cardiac vagal tone (p=0.023), while an ectomorphic build was related to higher cardiac vagal tone values as estimated by the 4-second exercise test (r=0.23; p=0.017). CONCLUSIONS: Non-obese and healthy adult men with unfavorable anthropometric characteristics tend to present lower cardiac vagal tone levels. Early identification of this trend by simple protocols that are non-invasive and risk-free, using select anthropometric characteristics, may be clinically useful in a global strategy to prevent cardiovascular disease. PMID:20126345

  7. Glomus vagale presenting as a supraclavicular mass: Magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Puvaneswary, M.; Gani, J. [John Hunter Hospital, New Lambton Heights, Newcastle, NSW (Australia). Departments of Medical Imaging and Surgery; Kalnins, I.K. [Westmead Hospital, Westmead, Sydney NSW (Australia)

    1998-11-01

    Glomus vagale are rare vascular tumours of the paraganglion cells of the vagus nerve, and they usually occur in the carotid space. Tumours can be familial, multicentric, malignant but rarely hormonally active. A rare case is reported of glomus vagale presenting as a supraclavicular mass. Copyright (1998) Blackwell Science Pty Ltd 12 refs., 3 figs.

  8. Spleen vagal denervation inhibits the production of antibodies to circulating antigens.

    Directory of Open Access Journals (Sweden)

    Ruud M Buijs

    Full Text Available BACKGROUND: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output. METHODOLOGY/PRINCIPAL FINDINGS: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS, activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA. CONCLUSIONS/SIGNIFICANCE: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.

  9. Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

    Science.gov (United States)

    Perry, Nicole B; Calkins, Susan D; Nelson, Jackie A; Leerkes, Esther M; Marcovitch, Stuart

    2012-07-01

    The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. Copyright © 2011 Wiley Periodicals, Inc.

  10. Vagal Sensory Neuron Subtypes that Differentially Control Breathing

    OpenAIRE

    Chang, Rui B.; Strochlic, David E.; Williams, Erika K.; Umans, Benjamin D.; Liberles, Stephen D.

    2015-01-01

    Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing. Genetically guided anatomical mapping revealed that these neurons densely innervate the lung and send long-range projections to different brainstem targets. Npy2r neurons a...

  11. Determining cardiac vagal threshold from short term heart rate complexity

    Directory of Open Access Journals (Sweden)

    Hamdan Rami Abou

    2016-09-01

    Full Text Available Evaluating individual aerobic exercise capacity is fundamental in sports and exercise medicine but associated with organizational and instrumental effort. Here, we extract an index related to common performance markers, the aerobic and anaerobic thresholds enabling the estimation of exercise capacity from a conventional sports watch supporting beatwise heart rate tracking. Therefore, cardiac vagal threshold (CVT was determined in 19 male subjects performing an incremental maximum exercise test. CVT varied around the anaerobic threshold AnT with mean deviation of 7.9 ± 17.7 W. A high correspondence of the two thresholds was indicated by Bland-Altman plots with limits of agreement −27.5 W and 43.4 W. Additionally, CVT was strongly correlated AnT (rp = 0.86, p < 0.001 and reproduced this marker well (rc = 0.81. We conclude, that cardiac vagal threshold derived from compression entropy time course can be useful to assess physical fitness in an uncomplicated way.

  12. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats

    OpenAIRE

    Xiao, Bo; Zanoun, Rami R.; Carvell, George E.; Simons, Daniel J.; Washington, Kia M.

    2016-01-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (...

  13. An investigation into the presence of a vagal tachycardia and the effect of vasoactive intestinal polypeptide on rat heart rate in vitro.

    Science.gov (United States)

    Hogan, K; Markos, F

    2006-01-01

    The presence of the vagal tachycardia and the effect of vasoactive intestinal polypeptide in the isolated innervated rat atrium were investigated. The right vagus, or cardiac branch, were stimulated at 4, 8, 16 and 32 Hz, pulse duration 1 ms, 20 V, 30 s before atropine and for 1 min after atropine (3 micromol/l), experiments were carried out in the presence of atenolol (4 micromol/l). No significant vagal tachycardia was observed in the presence of atropine, the greatest increase in heart rate was at 16 Hz which was 3+/-1 beats/min (n = 12 rats) (p = 0.052). Baseline heart rates for the control, 226+/-11 beats/min (n = 12 rats) and atropine experiments, 210+/-8 beats/min (n = 12 rats), were not significantly different (p = 0.24). VIP (0.06, 0.12, 0.24 micromol/l) caused a maximum increase of 27+/-13 beats/min (n = 5 rats) after 6 micromol/l VIP which was not significant, two higher concentrations of VIP failed to increase heart rate further. These results show that the vagal tachycardia is not present and that VIP does not cause a significant tachycardia in the rat. Copyright (c) 2006 S. Karger AG, Basel.

  14. Voltage-Dependent Currents in Isolated Vestibular Afferent Calyx Terminals

    National Research Council Canada - National Science Library

    Rennie, Katherine J; Streeter, Michele A

    ...; accepted in final form 6 September 2005 Na + currents were studied by whole cell patch clamp of chalice-shaped afferent terminals attached to type I hair cells isolated from the gerbil semicircular canal and utricle. Outward K...

  15. How to test for a relative afferent pupillary defect (RAPD

    Directory of Open Access Journals (Sweden)

    David C Broadway

    2017-03-01

    Full Text Available This article explains how careful examination of the pupil light reflex can reveal valuable information about the afferent (optic nerve and efferent (oculomotor nerve light reflex pathway, and hence the functioning of these two cranial nerves.

  16. Afferent diversity and the organization of central vestibular pathways

    OpenAIRE

    Goldberg, Jay M.

    2000-01-01

    This review considers whether the vestibular system includes separate populations of sensory axons innervating individual organs and giving rise to distinct central pathways. There is a variability in the discharge properties of afferents supplying each organ. Discharge regularity provides a marker for this diversity since fibers which differ in this way also differ in many other properties. Postspike recovery of excitability determines the discharge regularity of an afferent and its sensitiv...

  17. Differential central projections of vestibular afferents in pigeons

    Science.gov (United States)

    Dickman, J. D.; Fang, Q.

    1996-01-01

    The question of whether a differential distribution of vestibular afferent information to central nuclear neurons is present in pigeons was studied using neural tracer compounds. Discrete tracing of afferent fibers innervating the individual semicircular canal and otolith organs was produced by sectioning individual branches of the vestibular nerve that innervate the different receptor organs and applying crystals of horseradish peroxidase, or a horseradish peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and transport. Afferent fibers and their terminal distributions within the brainstem and cerebellum were visualized subsequently. Discrete areas in the pigeon central nervous system that receive primary vestibular input include the superior, dorsal lateral, ventral lateral, medial, descending, and tangential vestibular nuclei; the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal afferents projected heavily to medial regions in the superior and descending vestibular nuclei as well as the A group. Vertical canal projections to the medial and lateral vestibular nuclei were observed but were less prominent. Horizontal canal projections to the superior and descending vestibular nuclei were much more centrally located than those of the vertical canals. A more substantial projection to the medial and lateral vestibular nuclei was seen with horizontal canal afferents compared to vertical canal fibers. Afferents innervating the utricle and saccule terminated generally in the lateral regions of all vestibular nuclei in areas that were separate from the projections of the semicircular canals. In addition, utricular fibers projected to regions in the vestibular nuclei that overlapped with the horizontal semicircular canal terminal fields, whereas saccular afferents projected to regions that received vertical canal fiber terminations. Lagenar

  18. [Acute pancreatitis and afferent loop syndrome. Case report].

    Science.gov (United States)

    Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

    2013-01-01

    The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

  19. Static gamma-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats.

    Science.gov (United States)

    Gladden, M H; Matsuzaki, H

    2002-08-15

    Ideas about the functions of static gamma-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static gamma-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active gamma-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of gamma-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static gamma-motoneurones were active at low frequency (Activity of other static gamma-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of gamma-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single gamma-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of gamma-motoneurones on either the primary or the secondary ending, but not on both together. However, gamma-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in alpha-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents.

  20. Afferent innervation of the utricular macula in pigeons

    Science.gov (United States)

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  1. Renal and cardiovascular afferent inputs to hypothalamic paraventriculo-spinal neurons.

    Science.gov (United States)

    Caverson, M M; Ciriello, J

    1988-12-19

    Experiments were done in chloralose-anesthetized cats to identify single units in the paraventricular nucleus of the hypothalamus (PVH) that responded to stimulation of afferent renal nerves (ARN) and the buffer nerves (carotid sinus (CSN) and aortic depressor (ADN) nerves), and whose axons projected directly to thoracic spinal sympathetic areas. Of 426 single units tested in the PVH region, 20 were antidromically activated by stimulation of the spinal cord. Sixteen of these antidromic units (80%) responded orthodromically to stimulation of ARN and/or the buffer nerves; 6 units (30%) were excited by ARN stimulation only, 2 units (10%) were excited by both ARN and buffer nerve stimulation, and 6 units were excited and 2 inhibited by buffer nerve stimulation only. These data demonstrate that sensory information originating in renal and cardiovascular receptors alters the firing rate of PVH-spinal projecting neurons and suggest that this long renal-PVH reflex loop may contribute to the elevation of arterial pressure (AP) during conditions when ARN are activated.

  2. A giant vagal schwannoma with unusual extension from skull base to the mediastinum

    Directory of Open Access Journals (Sweden)

    Shenoy S Vijendra

    2015-01-01

    Full Text Available Cervical vagal schwannoma is an extremely rare neoplasm. Middle aged people are usually affected. These tumors usually present as asymptomatic masses. These tumors are almost always benign. Preoperative diagnosis of these lesions is important due to the morbidity associated with its excision. Preoperative tissue diagnosis is not accurate. The imaging modality can be done to assess the extent and for planning the treatment. Surgical excision with preservation of neural origin is the treatment option. Giant vagal schwannomas are extremely rare. Only one case has been reported in the literature till date. There has no reported case of extensive vagal schwannoma from skull base to the mediastinum. Here, we describe the asymptomatic presentation of an unusual appearing giant cervical vagal schwannoma with an extension from skull base to the mediastinum.

  3. Spinal μ-opioid receptor-sensitive lower limb muscle afferents determine corticospinal responsiveness and promote central fatigue in upper limb muscle.

    Science.gov (United States)

    Sidhu, Simranjit K; Weavil, Joshua C; Venturelli, Massimo; Garten, Ryan S; Rossman, Matthew J; Richardson, Russell S; Gmelch, Benjamin S; Morgan, David E; Amann, Markus

    2014-11-15

    We investigated the influence of group III/IV lower limb muscle afferents on the development of supraspinal fatigue and the responsiveness of corticospinal projections to an arm muscle. Eight males performed constant-load leg cycling exercise (80% peak power output) for 30 s (non-fatiguing) and to exhaustion (∼9 min; fatiguing) both under control conditions and with lumbar intrathecal fentanyl impairing feedback from μ-opioid receptor-sensitive lower limb muscle afferents. Voluntary activation (VA) of elbow flexors was assessed via transcranial magnetic stimulation (TMS) during maximum voluntary contraction (MVC) and corticospinal responsiveness was monitored via TMS-evoked potentials (MEPs) during a 25% MVC. Accompanied by a significant 5 ± 1% reduction in VA from pre- to post-exercise, elbow flexor MVC progressively decreased during the fatiguing trial (P muscle afferents, MVC and VA remained unchanged during fatiguing exercise (P > 0.3). MEPs decreased by 36 ± 6% (P lower corticospinal responsiveness during this short bout (P muscle fatigue, group III/IV-mediated leg muscle afferents facilitate responsiveness of the motor pathway to upper limb flexor muscles. By contrast, in the presence of cycling-induced leg fatigue, group III/IV locomotor muscle afferents facilitate supraspinal fatigue in remote muscle not involved in the exercise and disfacilitate, or inhibit, the responsiveness of corticospinal projections to upper limb muscles.

  4. Sensorimotor Integration During Motor Learning: Transcranial Magnetic Stimulation Studies.

    Science.gov (United States)

    Matur, Zeliha; Öge, A Emre

    2017-12-01

    The effect of sensory signals coming from skin and muscle afferents on the sensorimotor cortical networks is entitled as sensory-motor integration (SMI). SMI can be studied electrophysiologically by the motor cortex excitability changes in response to peripheral sensory stimulation. These changes include the periods of short afferent inhibition (SAI), afferent facilitation (AF), and late afferent inhibition (LAI). During the early period of motor skill acquisition, motor cortex excitability increases and changes occur in the area covered by the relevant zone of the motor cortex. In the late period, these give place to the morphological changes, such as synaptogenesis. SAI decreases during learning the motor skills, while LAI increases during motor activity. In this review, the role of SMI in the process of motor learning and transcranial magnetic stimulation techniques performed for studying SMI is summarized.

  5. Lower cardiac vagal tone in non-obese healthy men with unfavorable anthropometric characteristics

    Directory of Open Access Journals (Sweden)

    Plínio S. Ramos

    2010-01-01

    Full Text Available OBJECTIVES: to determine if there are differences in cardiac vagal tone values in non-obese healthy, adult men with and without unfavorable anthropometric characteristics. INTRODUCTION: It is well established that obesity reduces cardiac vagal tone. However, it remains unknown if decreases in cardiac vagal tone can be observed early in non-obese healthy, adult men presenting unfavorable anthropometric characteristics. METHODS: Among 1688 individuals assessed between 2004 and 2008, we selected 118 non-obese (BMI <30 kg/m², healthy men (no known disease conditions or regular use of relevant medications, aged between 20 and 77 years old (42 ± 12-years-old. Their evaluation included clinical examination, anthropometric assessment (body height and weight, sum of six skinfolds, waist circumference and somatotype, a 4-second exercise test to estimate cardiac vagal tone and a maximal cardiopulmonary exercise test to exclude individuals with myocardial ischemia. The same physician performed all procedures. RESULTS: A lower cardiac vagal tone was found for the individuals in the higher quintiles - unfavorable anthropometric characteristics - of BMI (p=0.005, sum of six skinfolds (p=0.037 and waist circumference (p<0.001. In addition, the more endomorphic individuals also presented a lower cardiac vagal tone (p=0.023, while an ectomorphic build was related to higher cardiac vagal tone values as estimated by the 4-second exercise test (r=0.23; p=0.017. CONCLUSIONS: Non-obese and healthy adult men with unfavorable anthropometric characteristics tend to present lower cardiac vagal tone levels. Early identification of this trend by simple protocols that are non-invasive and risk-free, using select anthropometric characteristics, may be clinically useful in a global strategy to prevent cardiovascular disease.

  6. Store-operated calcium entry in vagal sensory nerves is independent of Orai channels.

    Science.gov (United States)

    Hooper, Justin Shane; Hadley, Stephen H; Mathews, Adithya; Taylor-Clark, Thomas E

    2013-03-29

    Vagal sensory nerves innervate the majority of visceral organs (e.g., heart, lungs, GI tract, etc) and their activation is critical for defensive and regulatory reflexes. Intracellular Ca(2+) is a key regulator of neuronal excitability and is largely controlled by the Ca(2+) stores of the endoplasmic reticulum. In other cell types store-operated channels (SOC) have been shown to contribute to the homeostatic control of intracellular Ca(2+). Here, using Ca(2+) imaging, we have shown that ER depletion in vagal sensory neurons (using thapsigargin or caffeine) in the absence of extracellular Ca(2+) evoked Ca(2+) influx upon re-introduction of Ca(2+) into the extracellular buffer. This store-operated Ca(2+) entry (SOCE) was observed in approximately 25-40% of vagal neurons, equally distributed among nociceptive and non-nociceptive sensory subtypes. SOCE was blocked by Gd(3+) but not by the Orai channel blocker SKF96365. We found Orai channel mRNA in extracts from whole vagal ganglia, but when using single cell RT-PCR analysis we found only 3 out of 34 neurons expressed Orai channel mRNA, indicating that Orai channel expression in the vagal ganglia was likely derived from non-neuronal cell types. Confocal microscopy of vagal neurons in 3 day cultures demonstrated rich ER tracker fluorescence throughout axonal and neurite structures and ER store depletion (thapsigargin) evoked Ca(2+) transients from these structures. However, no SOCE could be detected in the axonal/neurite structures of vagal neurons. We conclude that SOCE occurs in vagal sensory neuronal cell bodies through non-Orai mechanisms but is absent at nerve terminals. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Favorable Swallowing Outcomes following Vagus Nerve Sacrifice for Vagal Schwannoma Resection.

    Science.gov (United States)

    Patel, Mira A; Eytan, Danielle F; Bishop, Justin; Califano, Joseph A

    2017-02-01

    Objective To determine the impact of unilateral vagal sacrifice for vagal schwannoma on postoperative swallowing function. Study Design Case series, chart review. Setting Academic medical institution. Subjects and Methods Ten patients underwent vagus nerve sacrifice for vagal schwannoma resection. Archived pathology records dating from 1985 through 2012 at our institution were retrospectively queried for cases of vagal schwannoma with vagus nerve sacrifice. Medical records were abstracted for demographic and disease information as well as cranial nerve and swallowing function. Preoperative and postoperative cranial nerve function, subjective and objective measures of swallowing function, Functional Oral Intake Scale (FOIS) level, and need for vocal fold medialization were variables collected. Data were analyzed with summary statistics. Results The patients who underwent vagal sacrifice for vagal schwannoma at our institution had a mean age of 42.3 years (median, 44 years; range, 15-63 years) and follow-up of 35.6 months (median, 9 months; range, 1-115 months). Most presented with no preoperative cranial nerve deficit or difficulty swallowing. Immediately postoperatively, 90% had a vagus nerve deficit, but 50% had no subjective difficulty swallowing, and 70% had a FOIS level of 7 at postoperative hospital discharge. Within 1 month after surgery, 70% had normal swallowing function according to a modified barium swallow study. A full diet was tolerated by mouth within an average of 2.7 days (median, 2 days; range, 1-6 days) after surgery in this cohort. Seventy percent required vocal fold medialization postoperatively for incomplete glottic closure. Conclusion Vagal nerve sacrifice during resection of vagal schwannoma can be performed with normal postoperative swallowing function.

  8. Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents.

    Science.gov (United States)

    Qiao, Guo-Fen; Li, Bai-Yan; Zhou, Yu-Hong; Lu, Yan-Jie; Schild, John H

    2009-01-01

    Persistent tetrodotoxin-resistant (TTX-R) Na(+) (Na(v)1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na(+) although the functional expression of this current was observed in the presence of PGE(2) or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na(+)). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na(+) currents were expressed in 9 out of 38 VANs bathed in 150 mM Na(+). The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV). This indicates that persistent TTX-R Na(+) channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

  9. High-frequency burst vagal nerve simulation therapy in a natural primate model of genetic generalized epilepsy.

    Science.gov (United States)

    Szabó, C Á; Salinas, F S; Papanastassiou, A M; Begnaud, J; Ravan, M; Eggleston, K S; Shade, R; Lutz, C; De La Garza, M

    2017-12-01

    Since the approval of Vagal Nerve Stimulation (VNS) Therapy for medically refractory focal epilepsies in 1997, it has been also reported to be effective for a wide range of generalized seizures types and epilepsy syndromes. Instead of conventional VNS Therapy delivered at 20-30Hz signal frequencies, this study evaluates efficacy and tolerability of high-frequency burst VNS in a natural animal model for genetic generalized epilepsy (GGE), the epileptic baboon. Two female baboons (B1 P.h. Hamadryas and B2 P.h. Anubis x Cynocephalus) were selected because of frequently witnessed generalized tonic-clonic seizures (GTCS) for VNS implantation. High-frequency burst VNS Therapy was initiated after a 4-5 week baseline; different VNS settings (0.25, 2 or 2.5mA, 300Hz, 4 vs 7 pulses, 0.5-2.5s interburst interval, and intermittent stimulation for 1-2 vs for 24h per day) were tested over the subsequent 19 weeks, which included a 4-6 week wash-out period. GTCS frequencies were quantified for each setting, while seizure duration and postictal recovery times were compared to baseline. Scalp EEG studies were performed at almost every setting, including intermittent light stimulation (ILS) to evaluate photosensitivity. Pre-ILS ictal and interictal discharge rates, as well as ILS responses were compared between trials. The Novel Object test was used to assess potential treatment effects on behavior. High-frequency burst VNS Therapy reduced GTCS frequencies at all treatment settings in both baboons, except when output currents were reduced (0.25mA) or intermittent stimulation was restricted (to 1-2h/day). Seizure duration and postictal recovery times were unchanged. Scalp EEG studies did not demonstrate treatment-related decrease of ictal or interictal epileptic discharges or photosensitivity, but continuous treatment for 120-180s during ILS appeared to reduce photoparoxysmal responses. High-frequency burst VNS Therapy was well-tolerated by both baboons, without cardiac or behavioral

  10. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure.

    Science.gov (United States)

    Wang, Han-Jun; Wang, Wei; Cornish, Kurtis G; Rozanski, George J; Zucker, Irving H

    2014-10-01

    The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympathoexcitation in chronic heart failure (CHF). Increased sympathoexcitation is positively related to mortality in patients with CHF. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here, we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. To delete the transient receptor potential vanilloid 1 receptor-expressing CSAR afferents selectively, epicardial application of resiniferatoxin (50 μg/mL), an ultrapotent analog of capsaicin, was performed during myocardium infarction surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of resiniferatoxin largely prevented the elevated left ventricle end-diastolic pressure, lung edema, and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart, and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that resiniferatoxin attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and transforming growth factor-β receptor I in CHF rats. Pressure-volume loop analysis showed that resiniferatoxin reduced the end-diastolic pressure volume relationships in CHF rats, indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF. © 2014 American Heart Association, Inc.

  11. Decoding of the spike timing of primary afferents during voluntary arm movements in monkeys

    Directory of Open Access Journals (Sweden)

    Tatsuya eUmeda

    2014-05-01

    Full Text Available Understanding the mechanisms of encoding forelimb kinematics in the activity of peripheral afferents is essential for determining the optimal parameters of afferent stimulation to transmit proprioceptive signals in neuroprosthetics. To investigate whether the spike timing of dorsal root ganglion (DRG neurons could be estimated from the forelimb kinematics of behaving monkeys, we implanted two multi-electrode arrays chronically in the DRGs at the level of the cervical segments in two monkeys. Neuronal activity during voluntary reach-to-grasp movements were recorded simultaneously with the trajectories of hand/arm movements, which were tracked in three-dimensional space using a motion capture system. Sixteen and 13 neurons, including muscle spindles, skin receptors, and tendon organ afferents, were recorded in the two monkeys, respectively. We were able to reconstruct forelimb joint kinematics from the temporal firing pattern of a subset of DRG neurons using sparse linear regression (SLiR analysis, suggesting that DRG neuronal ensembles encoded information about joint kinematics. Furthermore, we estimated the spike timing of the DRG neuronal ensembles from joint kinematics using an integrate-and-fire model (IF incorporating the SLiR algorithm. The temporal change of firing frequency of a subpopulation of neurons was reconstructed precisely from forelimb kinematics using the SLiR. The spike timing of the DRG neurons was calculated using an IF model, in which a spike occurs if the cumulative sum of the firing frequency value exceeded a constant threshold. The estimated firing pattern of the DRG neuronal ensembles encoded forelimb joint angles and velocities as precisely as the originally recorded neuronal activity. These results suggest that the simple model can be used to generate an accurate estimate of the spike timing of DRG neuronal ensembles from forelimb joint kinematics, and is useful for designing a proprioceptive decoder in a brain machine

  12. Synaptic transmission of chaotic spike trains between primary afferent fiber and spinal dorsal horn neuron in the rat.

    Science.gov (United States)

    Wan, Y-H; Jian, Z; Wen, Z-H; Wang, Y-Y; Han, S; Duan, Y-B; Xing, J-L; Zhu, J-L; Hu, S-J

    2004-01-01

    Primary sensory neurons can generate irregular burst firings in which the existence of significant deterministic behaviors of chaotic dynamics has been proved with nonlinear time series analysis. But how well the deterministic characteristics and neural information of presynaptic chaotic spike trains were transmitted into postsynaptic spike trains is still an open question. Here we investigated the synaptic transmission of chaotic spike trains between primary Adelta afferent fiber and spinal dorsal horn neuron. Two kinds of basic stimulus unit, brief burst and single pulse, were employed by us to comprise chaotic stimulus trains. For time series analysis, we defined "events" as the longest sequences of spikes with all interspike intervals less than or equal to a certain threshold and extracted the interevent intervals (IEIs) from spike trains. Return map analysis of the IEI series showed that the main temporal structure of chaotic input trains could be detected in postsynaptic output trains, especially under brief-burst stimulation. Using correlation dimension and nonlinear prediction methods, we found that synaptic transmission could influence the nonlinear characteristics of chaotic trains, such as fractal dimension and short-term predictability, with greater influence made under single-pulse stimulation. By calculating the mutual information between input and output trains, we found the information carried by presynaptic spike trains could not be completely transmitted at primary afferent synapses, and that brief bursts could more reliably transmit the information carried by chaotic input trains across synapses. These results indicate that although unreliability exists during synaptic transmission, the main deterministic characteristics of chaotic burst trains can be transmitted across primary afferent synapses. Moreover, brief bursts that come from the periphery can more reliably transmit neural information between primary afferent fibers and spinal dorsal horn

  13. Chloride regulates afferent arteriolar contraction in response to depolarization

    DEFF Research Database (Denmark)

    Hansen, P B; Jensen, B L; Skott, O

    1998-01-01

    -Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit...... afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel....... The results show that K+-induced contraction of smooth muscle cells in the afferent arteriole is highly sensitive to chloride, whereas neurotransmitter release and ensuing contraction is not dependent on chloride. Thus, there are different activation pathways for depolarizing vasoconstrictors...

  14. Relations between metabolic homeostasis, diet, and peripheral afferent neuron biology.

    Science.gov (United States)

    Dunn, Tamara N; Adams, Sean H

    2014-07-01

    It is well established that food intake behavior and energy balance are regulated by crosstalk between peripheral organ systems and the central nervous system (CNS), for instance, through the actions of peripherally derived leptin on hindbrain and hypothalamic loci. Diet- or obesity-associated disturbances in metabolic and hormonal signals to the CNS can perturb metabolic homeostasis bodywide. Although interrelations between metabolic status and diet with CNS biology are well characterized, afferent networks (those sending information to the CNS from the periphery) have received far less attention. It is increasingly appreciated that afferent neurons in adipose tissue, the intestines, liver, and other tissues are important controllers of energy balance and feeding behavior. Disruption in their signaling may have consequences for cardiovascular, pancreatic, adipose, and immune function. This review discusses the diverse ways that afferent neurons participate in metabolic homeostasis and highlights how changes in their function associate with dysmetabolic states, such as obesity and insulin resistance. © 2014 American Society for Nutrition.

  15. Determinants of spatial and temporal coding by semicircular canal afferents.

    Science.gov (United States)

    Highstein, Stephen M; Rabbitt, Richard D; Holstein, Gay R; Boyle, Richard D

    2005-05-01

    The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components-one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below.

  16. Afferent fibers of the pudendal nerve modulate sympathetic neurons controlling the bladder neck.

    Science.gov (United States)

    Reitz, André; Schmid, Daniel M; Curt, Armin; Knapp, Peter A; Schurch, Brigitte

    2003-01-01

    Pudendal nerve stimulation is known to have a potential modulative effect on bladder function. However, even if its efficiency has been established for various neurogenic and non-neurogenic bladder dysfunctions, the underlying neuronal mechanism, and the involved pathways in humans remain unknown. In this prospective study we focused on the effects of pudendal nerve stimulation in complete spinal cord injured patients to identify neuromodulative processes that occur on spinal level. Twenty complete spinal male presenting with upper motor neuron lesion and neurogenic incontinence underwent pudendal nerve stimulation. Bladder, bladder neck (BN), and external urethral sphincter (EUS) pressures were continuously recorded with a three channel microtip pressure transducer catheter. Fifty six pudendal stimulations using biphasic rectangular impulses (0.2 ms, 10 Hz) with intensities up to 100 mA were applied to the dorsal penile nerve. In six patients, 18 stimulations were repeated after intravenous (i.v.) administration of 7 mg phentolamine. Mean BN and EUS pressure increased during stimulation significantly (P stimulation significantly (P nerve stimulation evoked somatic responses in the EUS and autonomic responses in the smooth muscle sphincter controlling the BN. Longer latencies of the BN responses and the sensitivity to the alpha-blocking agent phentolamine suggest that sympathetic alpha-adrenergic fibers are involved. Somatic afferent fibers of the pudendal nerve are supposed to project on sympathetic thoracolumbar neurons to the BN and modulate their function. This neuromodulative effect works exclusively at the spinal level and appears to be at least partly responsible for BN competence and at least continence. Copyright 2003 Wiley-Liss, Inc.

  17. Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension.

    Science.gov (United States)

    Chen, W-W; Xiong, X-Q; Chen, Q; Li, Y-H; Kang, Y-M; Zhu, G-Q

    2015-04-01

    Persistent excessive sympathetic activation greatly contributes to the pathogenesis of chronic heart failure (CHF) and hypertension. Cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex with positive feedback characteristics. Humoral factors such as bradykinin, adenosine and reactive oxygen species produced in myocardium due to myocardial ischaemia stimulate cardiac sympathetic afferents and thereby reflexly increase sympathetic activity and blood pressure. The CSAR is enhanced in myocardial ischaemia, CHF and hypertension. The enhanced CSAR at least partially contributes to the sympathetic activation and pathogenesis of these diseases. Nucleus of the solitary tract (NTS), hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla are the most important central sites involved in the modulation and integration of the CSAR. Angiotensin II, AT1 receptors and NAD(P)H oxidase-derived superoxide anions pathway in the PVN are mainly responsible for the enhanced CSAR in CHF and hypertension. Central angiotensin-(1-7), nitric oxide, endothelin, intermedin, hydrogen peroxide and several other signal molecules are involved in regulating CSAR. Blockade of the CSAR shows beneficial effects in CHF and hypertension. This review focuses on the anatomical and physiological basis of the CSAR, the interaction of CSAR with baroreflex and chemoreflex, and the role of enhanced CSAR in the pathogenesis of CHF and hypertension. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  18. Vagus Nerve Stimulation

    Science.gov (United States)

    Howland, Robert H.

    2014-01-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality. PMID:24834378

  19. Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli

    Directory of Open Access Journals (Sweden)

    Kim Elmer K

    2012-07-01

    observed in afferent recordings. Finally, the SAI afferent’s characteristic response of producing irregular ISIs is shown to be controllable via manipulating the output filtering from the sensor or adding stochastic noise. Conclusions This integrated engineering approach extends prior works focused upon neural dynamics and vibration. Future efforts will perfect measures of performance, such as first spike latency and irregular ISIs, and link the generation of characteristic features within trains of action potentials with current pulse waveforms that stimulate single action potentials at the peripheral afferent.

  20. Coding of stimuli by ampullary afferents in Gnathonemus petersii.

    Science.gov (United States)

    Engelmann, J; Gertz, S; Goulet, J; Schuh, A; von der Emde, G

    2010-10-01

    Weakly electric fish use electroreception for both active and passive electrolocation and for electrocommunication. While both active and passive electrolocation systems are prominent in weakly electric Mormyriform fishes, knowledge of their passive electrolocation ability is still scarce. To better estimate the contribution of passive electric sensing to the orientation toward electric stimuli in weakly electric fishes, we investigated frequency tuning applying classical input-output characterization and stimulus reconstruction methods to reveal the encoding capabilities of ampullary receptor afferents. Ampullary receptor afferents were most sensitive (threshold: 40 μV/cm) at low frequencies (thresholds were one order of magnitude higher. The integration of simultaneously recorded afferents of similar frequency-tuning resulted in strongly enhanced signal-to-noise ratios and increased mutual information rates but did not increase the range of frequencies detectable by the system. Theoretically the neuronal integration of input from receptors experiencing opposite polarities of a stimulus (left and right side of the fish) was shown to enhance encoding of such stimuli, including an increase of bandwidth. Covariance and coherence analysis showed that spiking of ampullary afferents is sufficiently explained by the spike-triggered average, i.e., receptors respond to a single linear feature of the stimulus. Our data support the notion of a division of labor of the active and passive electrosensory systems in weakly electric fishes based on frequency tuning. Future experiments will address the role of central convergence of ampullary input that we expect to lead to higher sensitivity and encoding power of the system.

  1. Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Herzog, Walter; Block, Joel A

    2011-01-01

    Lower-extremity muscle strength and afferent sensory dysfunction, such as reduced proprioceptive acuity, are potentially modifiable putative risk factors for knee osteoarthritis (OA). Findings from current studies suggest that muscle weakness is a predictor of knee OA onset, while there is confli...

  2. Cellular mechanisms for presynaptic inhibition of sensory afferents

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; delgado-lezama, rodolfo; Christensen, Rasmus Kordt

    of blockers for the GABA transporters 1 & 3 (GAT), the DRP was strongly reduced. Since GAT3 is mainly expressed in astrocytes, our results suggest that these glial cells are part of the microcircuit that controls the activity of primary afferents. Addition of the potent chloride channel blocker NPPB also...

  3. DMPD: Afferent pathways of pyrogen signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9917870 Afferent pathways of pyrogen signaling. Blatteis CM, Sehic E, Li S. Ann N Y... Acad Sci. 1998 Sep 29;856:95-107. (.png) (.svg) (.html) (.csml) Show Afferent pathways of pyrogen signaling.... PubmedID 9917870 Title Afferent pathways of pyrogen signaling. Authors Blatteis CM, Sehic E, Li S. Publica

  4. Low vagal tone magnifies the association between psychosocial stress exposure and internalizing psychopathology in adolescents.

    Science.gov (United States)

    McLaughlin, Katie A; Rith-Najarian, Leslie; Dirks, Melanie A; Sheridan, Margaret A

    2015-01-01

    Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13-17; N = 168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients.

  5. Slit/Robo-mediated chemorepulsion of vagal sensory axons in the fetal gut.

    Science.gov (United States)

    Goldberg, David; Borojevic, Rajka; Anderson, Monique; Chen, Jason J; Gershon, Michael D; Ratcliffe, Elyanne M

    2013-01-01

    The vagus nerve descends from the brain to the gut during fetal life to reach specific targets in the bowel wall. Vagal sensory axons have been shown to respond to the axon guidance molecule netrin and to its receptor, deleted in colorectal cancer (DCC). As there are regions of the gut wall into which vagal axons do and do not extend, it is likely that a combination of attractive and repellent cues are involved in how vagal axons reach specific targets. We tested the hypothesis that Slit/Robo chemorepulsion can contribute to the restriction of vagal sensory axons to specific targets in the gut wall. Transcripts encoding Robo1 and Robo2 were expressed in the nodose ganglia throughout development and mRNA encoding the Robo ligands Slit1, Slit2, and Slit3 were all found in the fetal and adult bowel. Slit2 protein was located in the outer gut mesenchyme in regions that partially overlap with the secretion of netrin-1. Neurites extending from explanted nodose ganglia were repelled by Slit2. These observations suggest that vagal sensory axons are responsive to Slit proteins and are thus repelled by Slits secreted in the gut wall and prevented from reaching inappropriate targets. Copyright © 2012 Wiley Periodicals, Inc.

  6. Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents

    Science.gov (United States)

    McLaughlin, Katie A.; Rith-Najarian, Leslie; Dirks, Melanie A.; Sheridan, Margaret A.

    2014-01-01

    Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13–17; N =168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients. PMID:24156380

  7. Electrical Grounding Improves Vagal Tone in Preterm Infants.

    Science.gov (United States)

    Passi, Rohit; Doheny, Kim K; Gordin, Yuri; Hinssen, Hans; Palmer, Charles

    2017-01-01

    Low vagal tone (VT) is a marker of vulnerability to stress and the risk of developing necrotizing enterocolitis in preterm infants. Electric fields produced by equipment in the neonatal intensive care unit (NICU) induce an electric potential measurable on the skin in reference to ground. An electrical connection to ground reduces the skin potential and improves VT in adults. We aimed to measure the electric field strengths in the NICU environment and to determine if connecting an infant to electrical ground would reduce the skin potential and improve VT. We also wished to determine if the skin potential correlated with VT. Environmental magnetic flux density (MFD) was measured in and around incubators. Electrical grounding (EG) was achieved with a patch electrode and wire that extended to a ground outlet. We measured the skin potential in 26 infants and heart rate variability in 20 infants before, during, and after grounding. VT was represented by the high-frequency power of heart rate variability. The background MFD in the NICU was below 0.5 mG, but it ranged between 1.5 and 12.7 mG in the closed incubator. A 60-Hz oscillating potential was recorded on the skin of all infants. With EG, the skin voltage dropped by about 95%. Pre-grounding VT was inversely correlated with the skin potential. VT increased by 67% with EG. After grounding, the VT fell to the pre-grounding level. The electrical environment affects autonomic balance. EG improves VT and may improve resilience to stress and lower the risk of neonatal morbidity in preterm infants. © 2017 S. Karger AG, Basel.

  8. The eloquence of silent cortex: analysis of afferent input to deafferented cortex in arm amputees.

    Science.gov (United States)

    Mackert, Bruno-Marcel; Sappok, Tanja; Grüsser, Sabine; Flor, Herta; Curio, Gabriel

    2003-03-03

    Cortical reorganisation after limb amputation includes topographic displacements of body representation areas and changes of areal extent. Remarkably, truncated nerves, which had innervated amputated limb parts and remained in the residual limbs, can retain access to the deafferented somatosensory cortex. Using somatosensory evoked potentials (SEP) we characterized afferences from electrically stimulated truncated nerves to the brachial plexus and cortex in 12 arm amputees. While peripheral responses were highly variable, thalamocortical input to S-1, as reflected by the primary cortical SEP component, was present in 11 of 12 patients. Despite long-term deafferentation, macroscopic phenomena of inhibition/refractoriness, as assessed by stimulus rate variations, appeared to be changed only marginally. Thus, deafferented cortex remains responsive when given artificial phantom input and could provide a neuronal substrate for spontaneous phantom limb sensations, including phantom pain.

  9. Redundant signaling mechanisms contribute to the vasodilatory response of the afferent arteriole to proteinase-activated receptor-2.

    Science.gov (United States)

    Wang, Xuemei; Hollenberg, Morley D; Loutzenhiser, Rodger

    2005-01-01

    We previously demonstrated that stimulation of proteinase-activated receptor-2 (PAR-2) by SLIGRL-NH(2) elicits afferent arteriolar vasodilation, in part, by elaborating nitric oxide (NO), suggesting an endothelium-dependent mechanism (Trottier G, Hollenberg M, Wang X, Gui Y, Loutzenhiser K, and Loutzenhiser R. Am J Physiol Renal Physiol 282: F891-F897, 2002). In the present study, we characterized the NO-independent component of this response, using the in vitro perfused hydronephrotic rat kidney. SLIGRL-NH(2) (10 mumol/l) dilated afferent arterioles preconstricted with ANG II, and the initial transient component of this response was resistant to NO synthase (NOS) and cyclooxygenase inhibition. This NO-independent response was not prevented by treatment with 10 nmol/l charybdotoxin and 1 mumol/l apamin, a manipulation that prevents the endothelium-derived hyperpolarizing factor (EDHF)-like response of the afferent arteriole to acetylcholine, nor was it blocked by the addition of 1 mmol/l tetraethylammonium (TEA) or 50 mumol/l 17-octadecynoic acid, treatments that block the EDHF-like response to bradykinin. To determine whether the PAR-2 response additionally involves the electrogenic Na(+)-K(+)-ATPase, responses were evaluated in the presence of 3 mmol/l ouabain. In this setting, SLIGRL-NH(2) induced a biphasic dilation in control and a transient response after NOS inhibition. The latter was not prevented by charybdotoxin plus apamin or by TEA alone but was abolished by combined treatment with charybdotoxin, apamin, and TEA. This treatment did not prevent the NO-dependent dilation evoked in the absence of NOS inhibition. Our findings indicate a remarkable redundancy in the signaling cascade mediating PAR-2 -induced afferent arteriolar vasodilation, suggesting an importance in settings such as inflamation or ischemia, in which vascular mechanisms might be impaired and the PAR system is thought to be activated.

  10. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.

    Science.gov (United States)

    Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-11-01

    We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

  11. Sympathetic modulation of muscle spindle afferent sensitivity to stretch in rabbit jaw closing muscles.

    Science.gov (United States)

    Roatta, S; Windhorst, U; Ljubisavljevic, M; Johansson, H; Passatore, M

    2002-04-01

    Previous reports showed that sympathetic stimulation affects the activity of muscle spindle afferents (MSAs). The aim of the present work is to study the characteristics of sympathetic modulation of MSA response to stretch: (i) on the dynamic and static components of the stretch response, and (ii) on group Ia and II MSAs to evaluate potentially different effects. In anaesthetised rabbits, the peripheral stump of the cervical sympathetic nerve (CSN) was stimulated at 10 impulses s(-1) for 45-90 s. The responses of single MSAs to trapezoidal displacement of the mandible were recorded from the mesencephalic trigeminal nucleus. The following characteristic parameters were determined from averaged trapezoidal responses: initial frequency (IF), peak frequency at the end of the ramp (PF), and static index (SI). From these, other parameters were derived: dynamic index (DI = PF - SI), dynamic difference (DD = PF - IF) and static difference (SD = SI - IF). The effects of CSN stimulation were also evaluated during changes in the state of intrafusal muscle fibre contraction induced by succinylcholine and curare. In a population of 124 MSAs, 106 units (85.4 %) were affected by sympathetic stimulation. In general, while changes in resting discharge varied among different units (Ia vs. II) and experimental conditions (curarised vs. non-curarised), ranging from enhancement to strong depression of firing, the amplitude of the response to muscle stretches consistently decreased. This was confirmed and detailed in a quantitative analysis performed on 49 muscle spindle afferents. In both the non-curarised (23 units) and curarised (26 units) condition, stimulation of the CSN reduced the response amplitude in terms of DD and SD, but hardly affected DI. The effects were equally present in both Ia and II units; they were shown to be independent from gamma drive and intrafusal muscle tone and not secondary to muscle hypoxia. Sympathetic action on the resting discharge (IF) was less

  12. Parenting Stressors and Young Adolescents’ Depressive Symptoms: Does High Vagal Suppression Offer Protection?

    Science.gov (United States)

    Fletcher, Anne C.; Buehler, Cheryl; Buchanan, Christy M.; Weymouth, Bridget B.

    2017-01-01

    Grounded in a dual-risk, biosocial perspective of developmental psychopathology, this study examined the role of higher vagal suppression in providing young adolescents protection from four parenting stressors. It was expected that lower vagal suppression would increase youth vulnerability to the deleterious effects of these parenting stressors. Depressive symptoms were examined as a central marker of socioemotional difficulties during early adolescence. The four parenting stressors examined were interparental hostility, maternal use of harsh discipline, maternal inconsistent discipline, and maternal psychological control. Participants were 68 young adolescents (Grade 6) and their mothers. Greater vagal suppression provided protection (i.e., lower depressive symptoms) from interparental hostility, harsh discipline, and maternal psychological control for boys but not for girls. PMID:27979628

  13. Peakonsul Jaanus Kirikmäe andis teenetemärgi praost Thomas Vagale / Airi Vaga ; foto: Harold Karu

    Index Scriptorium Estoniae

    Vaga, Airi, 1940-

    2008-01-01

    President Toomas Hendrik Ilves annetas iseseisvuspäeva puhul USA I praostkonna praostile Thomas Vagale Valgetähe IV klassi teenetemärgi. Teenetemärgi andis Thomas Vagale üle Eesti Vabariigi peakonsul Jaanus Kirikmäe

  14. The interactive effect of change in perceived stress and trait anxiety on vagal recovery from cognitive challenge

    Science.gov (United States)

    Crowley, Olga V.; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Ryff, Carol D.; Weinstein, Maxine; Seeman, Teresa E.; Sloan, Richard P.

    2012-01-01

    The present study tested the hypothesis that the change in state negative affect (measured as perceived stress) after cognitive challenge moderates the relationship of trait anxiety and anger to vagal recovery from that challenge. Cardiac vagal control (assessed using heart rate variability) and respiratory rate were measured in a sample of 905 participants from the Midlife in the United States Study. Cognitive challenges consisted of computerized mental arithmetic and Stroop color-word matching tasks. Multiple regression analyses controlling for the effects of the demographic, lifestyle, and medical factors influencing cardiac vagal control showed a significant moderating effect of change in perceived stress on the relationship of trait anxiety to vagal recovery from cognitive challenges (Beta = .253, p= .013). After adjustment for respiratory rate, this effect became marginally significant (Beta = .177, p= .037). In contrast, for the relationship of trait anger to vagal recovery, this effect was not significant either before (Beta = .141, p=.257) or after (Beta = .186, p=.072) adjusting for respiratory rate. Secondary analyses revealed that among the individuals with higher levels of trait anxiety, greater reductions in perceived stress were associated with greater increases in cardiac vagal control after the challenge. In contrast, among the individuals with lower levels of trait anxiety, changes in perceived stress had no impact on vagal recovery. Therefore, change in perceived stress moderates the relationship of trait anxiety, but not trait anger, to vagal recovery from cognitive challenge. PMID:21945037

  15. Relationship between vagal withdrawaland reactivation indices and aerobic capacity in taekwondo athletes

    Directory of Open Access Journals (Sweden)

    Luiz Augusto Perandini

    2010-01-01

    Full Text Available The aim of this study was to evaluate the relationship between vagal withdrawal and reactivation indices and maximal running velocity (Vmax in taekwondo athletes. Eleven elite taekwondo athletes (seven men: 23.7±2.2 years, 72.4±7.0 kg, 178.8±7.5 cm, 51.9±2.9 ml.kg-1.min-1, and four women: 18.8±1.5 years, 61.8±1.8 kg, 168.0±4.4 cm, 41.6±2.4 ml.kg-1.min-1 performed a graded exercise test until exhaustion, with the last complete stage performed corresponding to Vmax. Heart rate variability (HRV parameters were calculated at 1-minute intervals until 85% of maximum HR and plotted against time for the estimation of vagal withdrawal indices (τ, amplitude (A and area under the curve (AUC. Vagal reactivation indices were determined based on HR recovery during the first 60 s (HRR60s and negative reciprocal of the slope of the regression line obtained during the first 30 s of HRR (T30. The vagal withdrawal parameters A and AUC were moderately and significantly correlated with Vmax (r = 0.61-0.71, P 0.05. T30 and HRR60s were also significantly correlated with Vmax (r = -0.77 and 0.64, P < 0.05, respectively. The present results showed that vagal withdrawal (A and AUC and vagal reactivation (T30 and HRR60s indices were significantly correlated with Vmax, suggesting that these indices can be used for the evaluation and monitoring of aerobic fitness in taekwondo athletes.

  16. Comparison of the expression of c-fos, nur77 and egr1 mRNAs in rat hypothalamic magnocellular neurons and their putative afferent projection neurons: cell- and stimulus-specific induction.

    Science.gov (United States)

    Luckman, S M

    1997-11-01

    Hypothalamic magnocellular neurons and their afferent inputs provide a model system in which to study the regulation of inducible transcription factors in the brain in vivo. Osmotic stimulation of rats produced by graded infusions of saline at different tonicities was found to lead to the induction of c-fos, nur77 and egr1 mRNAs in magnocellular neurons, as well as in putative afferent neurons, including those in structures of the forebrain (subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis). The results presented suggest that stronger levels of osmotic stimulation recruit additional afferents from the forebrain and brainstem that can act on magnocellular neurons via alternative receptors. A single systemic injection of the peptide cholecystokinin produced robust induction of c-fos and nur77 mRNAs in afferent neurons of the brainstem nucleus tractus solitarii and in magnocellular neurons. Despite the fact that these two neuronal populations are clearly electrically active, egr1 was not induced by this stimulus, providing examples of cell- and stimulus-specificity of its expression. This study re-emphasizes that the induction of transcription factors is largely dependent on the nature of the afferent input and does not correlate necessarily to the electrical activity of the neuron.

  17. Vagal nerve endings in visceral pleura and triangular ligaments of the rat lung.

    Science.gov (United States)

    Wang, Feng-Bin; Liao, Yi-Han; Wang, Yao-Chen

    2017-02-01

    The inner thoracic cavity is lined by the parietal pleura, and the lung lobes are covered by the visceral pleura. The parietal and visceral plurae form the pleural cavity that has negative pressure within to enable normal respiration. The lung tissues are bilaterally innervated by vagal and spinal nerves, including sensory and motor components. This complicated innervation pattern has made it difficult to discern the vagal vs. spinal processes in the pulmonary visceral pleura. With and without vagotomy, we identified vagal nerve fibres and endings distributed extensively in the visceral pleura ('P'-type nerve endings) and triangular ligaments ('L'-type nerve endings) by injecting wheat germ agglutinin-horseradish peroxidase as a tracer into the nucleus of solitary tract or nodose ganglion of male Sprague-Dawley rats. We found the hilar and non-hilar vagal pulmonary pleural innervation pathways. In the hilar pathway, vagal sub-branches enter the hilum and follow the pleural sheet to give off the terminal arborizations. In the non-hilar pathway, vagal sub-branches run caudally along the oesophagus and either directly enter the ventral-middle-mediastinal left lobe or follow the triangular ligaments to enter the left and inferior lobe. Both vagi innervate: (i) the superior, middle and accessory lobes on the ventral surfaces that face the heart; (ii) the dorsal-rostral superior lobe; (iii) the dorsal-caudal left lobe; and (iv) the left triangular ligament. Innervated only by the left vagus is: (i) the ventral-rostral and dorsal-rostral left lobe via the hilar pathway; (ii) the ventral-middle-mediastinal left lobe and the dorsal accessory lobe that face the left lobe via the non-hilar pathway; and (iii) the ventral-rostral inferior lobe that faces the heart. Innervated only by the right vagus, via the non-hilar pathway, is: (i) the inferior (ventral and dorsal) and left (ventral only) lobe in the area near the triangular ligament; (ii) the dorsal-middle-mediastinal left

  18. Modeling the nonlinear dynamic interactions of afferent pathways in the dentate gyrus of the hippocampus.

    Science.gov (United States)

    Dimoka, Angelika; Courellis, Spiros H; Marmarelis, Vasilis Z; Berger, Theodore W

    2008-05-01

    The dentate gyrus is the first region of the hippocampus that receives and integrates sensory information (e.g., visual, auditory, and olfactory) via the perforant path, which is composed of two distinct neuronal pathways: the Lateral Perforant Path (LPP) and the Medial Perforant Path (MPP). This paper examines the nonlinear dynamic interactions among arbitrary stimulation patterns at these two afferent pathways and their combined effect on the resulting response of the granule cells at the dentate gyrus. We employ non-parametric Poisson-Volterra models that serve as canonical quantitative descriptors of the nonlinear dynamic transformations of the neuronal signals propagating through these two neuronal pathways. These Poisson-Volterra models are estimated in the so-called "reduced form" with experimental data from in vitro hippocampal slices and provide excellent predictions of the electrophysiological activity of the granule cells in response to arbitrary stimulation patterns. The data are acquired through a custom-made multi-electrode-array system, which stimulated simultaneously the two pathways with random impulse trains and recorded the neuronal postsynaptic activity at the granule cell layer. The results of this study show that significant nonlinear interactions exist between the LPP and the MPP that may be critical for the integration of sensory information performed by the dentate gyrus of the hippocampus.

  19. Afferent activity to necklace glomeruli is dependent on external stimuli

    Directory of Open Access Journals (Sweden)

    Munger Steven D

    2009-03-01

    Full Text Available Abstract Background The main olfactory epithelium (MOE is a complex organ containing several functionally distinct subpopulations of sensory neurons. One such subpopulation is distinguished by its expression of the guanylyl cyclase GC-D. The axons of GC-D-expressing (GC-D+ neurons innervate 9–15 "necklace" glomeruli encircling the caudal main olfactory bulb (MOB. Chemosensory stimuli for GC-D+ neurons include two natriuretic peptides, uroguanylin and guanylin, and CO2. However, the biologically-relevant source of these chemostimuli is unclear: uroguanylin is both excreted in urine, a rich source of olfactory stimuli for rodents, and expressed in human nasal epithelium; CO2 is present in both inspired and expired air. Findings To determine whether the principal source of chemostimuli for GC-D+ neurons is external or internal to the nose, we assessed the consequences of removing external chemostimuli for afferent activity to the necklace glomeruli. To do so, we performed unilateral naris occlusions in Gucy2d-Mapt-lacZ +/- mice [which express a β-galactosidase (β-gal reporter specifically in GC-D+ neurons] followed by immunohistochemistry for β-gal and a glomerular marker of afferent activity, tyrosine hydroxylase (TH. We observed a dramatic decrease in TH immunostaining, consistent with reduced or absent afferent activity, in both necklace and non-necklace glomeruli ipsilateral to the occluded naris. Conclusion Like other MOB glomeruli, necklace glomeruli exhibit a large decrease in afferent activity upon removal of external stimuli. Thus, we conclude that activity in GC-D+ neurons, which specifically innervate necklace glomeruli, is not dependent on internal stimuli. Instead, GC-D+ neurons, like other OSNs in the MOE, primarily sense the external world.

  20. The role of peripheral afferents in persistent inguinal postherniorrhaphy pain

    DEFF Research Database (Denmark)

    Wijayasinghe, N; Ringsted, T K; Bischoff, J M

    2016-01-01

    BACKGROUND: Severe, persistent inguinal postherniorrhaphy pain (PIPP) is a debilitating condition that develops in 2-5% of patients. PIPP may be neuropathic in nature, yet the lesion in the peripheral nervous system has not been located. Most PIPP-patients demonstrate a tender point (TP......, was demonstrated. CONCLUSIONS: This trial demonstrates that peripheral afferent input from the TP-area is important for maintenance of spontaneous and evoked pain in PIPP. CLINICAL TRIAL REGISTRATION: NCT02065219....

  1. How to test for a relative afferent pupillary defect (RAPD)

    OpenAIRE

    David C Broadway

    2016-01-01

    The 'swinging light test' is used to detect a relative afferent pupil defect (RAPD): a means of detecting differences between the two eyes in how they respond to a light shone in one eye at a time. The test can be very useful for detecting unilateral or asymmetrical disease of the retina or optic nerve (but only optic nerve disease that occurs in front of the optic chiasm).

  2. How to test for a relative afferent pupillary defect (RAPD

    Directory of Open Access Journals (Sweden)

    David C Broadway

    2012-01-01

    Full Text Available The 'swinging light test' is used to detect a relative afferent pupil defect (RAPD: a means of detecting differences between the two eyes in how they respond to a light shone in one eye at a time. The test can be very useful for detecting unilateral or asymmetrical disease of the retina or optic nerve (but only optic nerve disease that occurs in front of the optic chiasm.

  3. Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

    OpenAIRE

    Idaira eOliva; Matthew eWanat

    2016-01-01

    Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA), a midbrain structure comprised of dopamine, GABA, and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects o...

  4. The pattern of excitation of human lower limb motoneurones by probable group II muscle afferents.

    Science.gov (United States)

    Simonetta-Moreau, M; Marque, P; Marchand-Pauvert, V; Pierrot-Deseilligny, E

    1999-05-15

    1. Heteronymous group II effects were investigated in the human lower limb. Changes in firing probability of single motor units in quadriceps (Q), biceps (Bi), semitendinosus (ST), gastrocnemius medialis (GM) and tibialis anterior (TA) were studied after electrical stimuli between 1 and 3 times motor threshold (MT) applied to common peroneal (CP), superficial (SP) and deep (DP) peroneal, Bi and GM nerves in those nerve-muscle combinations without recurrent inhibition. 2. Stimulation of the CP and Bi nerves evoked in almost all of the explored Q motor units a biphasic excitation with a low-threshold early peak, attributable to non-monosynaptic group I excitation, and a higher threshold late peak. When the CP nerve was cooled (or the stimulation applied to a distal branch, DP), the increase in latency was greater for the late than for the early peak, indicating that the late excitation is due to stimulation of afferents with a slower conduction velocity than group I fibres, presumably in the group II range. In ST motor units the group II excitation elicited by stimulation of the GM and SP nerves was particularly large and frequent, and the non-monosynaptic group I excitation was often replaced by an inhibition. 3. A late group II-induced excitation from CP to Q motoneurones and from GM and SP to ST motoneurones was also observed when using the H reflex as a test. 4. The electrical threshold and conduction velocity of the largest diameter fibres evoking the group II excitation were estimated to be 2.1 and 0.65 times those of the fastest Ia afferents, respectively. In the combinations tested in the present investigation the group II input seemed to be primarily of muscle origin. 5. The potent heteronymous group II excitation of motoneurones of both flexors and extensors of the knee contrasted with the absence of a group II effect from DP to GM and from GM to TA. In none of the combinations explored was there any evidence for group II inhibition of motoneurones. The

  5. The visceromotor and somatic afferent nerves of the penis.

    Science.gov (United States)

    Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

    2015-05-01

    Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

  6. Adipose afferent reflex: sympathetic activation and obesity hypertension.

    Science.gov (United States)

    Xiong, X-Q; Chen, W-W; Zhu, G-Q

    2014-03-01

    Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Afferent input selects NMDA receptor subtype to determine the persistency of hippocampal LTP in freely behaving mice

    Directory of Open Access Journals (Sweden)

    Jesús Javier Ballesteros

    2016-10-01

    Full Text Available The glutamatergic N-methyl-D-aspartate receptor (NMDAR is critically involved in many forms of hippocampus-dependent memory that may be enabled by synaptic plasticity. Behavioral studies with NMDAR antagonists and NMDAR subunit (GluN2 mutants revealed distinct contributions from GluN2A- and GluN2B-containing NMDARs to rapidly and slowly acquired memory performance. Furthermore, studies of synaptic plasticity, in genetically modified mice in vitro, suggest that GluN2A and GluN2B may contribute in different ways to the induction and longevity of synaptic plasticity. In contrast to the hippocampal slice preparation, in behaving mice, the afferent frequencies that induce synaptic plasticity are very restricted and specific. In fact, it is the stimulus pattern, and not variations in afferent frequency that determine the longevity of long-term potentiation (LTP. Here, we explored the contribution of GluN2A and GluN2B to LTP of differing magnitudes and persistencies in freely behaving mice. We applied differing high-frequency stimulation (HFS patterns at 100 Hz to the hippocampal CA1 region, to induce NMDAR-dependent LTP in wild-type (WT mice, that endured for 24h (late (L-LTP. In GluN2A-KO mice, E-LTP (HFS, 50 pulses was significantly reduced in magnitude and duration, whereas LTP (HFS, 2 x 50 pulses and L-LTP (HFS, 4 x 50 pulses were unaffected compared to responses in WT animals. By contrast, pharmacological antagonism of GluN2B in WT had no effect on E-LTP but significantly prevented LTP. E- LTP and LTP were significantly impaired by GluN2B antagonism in GluN2A-KO mice. These data indicate that the pattern of afferent stimulation is decisive for the recruitment of distinct GluN2A and GluN2B signaling pathways that in turn determine the persistency of hippocampal LTP. Whereas brief bursts of patterned stimulation preferentially recruit GluN2A and lead to weak and short-lived forms of LTP, prolonged, more intense, afferent activation recruits GluN2B

  8. Serotonin controls initiation of locomotion and afferent modulation of coordination via 5-HT7 receptors in adult rats.

    Science.gov (United States)

    Cabaj, Anna M; Majczyński, Henryk; Couto, Erika; Gardiner, Phillip F; Stecina, Katinka; Sławińska, Urszula; Jordan, Larry M

    2017-01-01

    paralysis of hindlimbs. This occurred without a direct effect on motoneurons as revealed by an investigation of reflex activity. The antagonist disrupted intra- and interlimb coordination during locomotion in all intact animals but not during fictive locomotion induced by stimulation of the mesencephalic locomotor region (MLR). MLR-evoked fictive locomotion was transiently blocked, then the amplitude and frequency of rhythmic activity were reduced by SB269970, consistent with the notion that the MLR activates 5-HT neurons, leading to excitation of central pattern generator neurons with 5-HT7 receptors. Effects on coordination in adults required the presence of afferent input, suggesting a switch to 5-HT7 receptor-mediated control of sensory pathways during development. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  9. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    Science.gov (United States)

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

    2014-06-01

    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  10. Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

    Science.gov (United States)

    Zila, I; Mokra, D; Kopincova, J; Kolomaznik, M; Javorka, M; Calkovska, A

    2017-09-22

    Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

  11. Vagal Reactions during Cryoballoon-Based Pulmonary Vein Isolation: A Clue for Autonomic Nervous System Modulation?

    Directory of Open Access Journals (Sweden)

    Michaël Peyrol

    2016-01-01

    Full Text Available Although paroxysmal atrial fibrillation (AF is known to be initiated by rapid firing of pulmonary veins (PV and non-PV triggers, the crucial role of cardiac autonomic nervous system (ANS in the initiation and maintenance of AF has long been appreciated in both experimental and clinical studies. The cardiac intrinsic ANS is composed of ganglionated plexi (GPs, located close to the left atrium-pulmonary vein junctions and a vast network of interconnecting neurons. Ablation strategies aiming for complete PV isolation (PVI remain the cornerstone of AF ablation procedures. However, several observational studies and few randomized studies have suggested that GP ablation, as an adjunctive strategy, might achieve better clinical outcomes in patients undergoing radiofrequency-based PVI for both paroxysmal and nonparoxysmal AF. In these patients, vagal reactions (VR such as vagally mediated bradycardia or asystole are thought to reflect intrinsic cardiac ANS modulation and/or denervation. Vagal reactions occurring during cryoballoon- (CB- based PVI have been previously reported; however, little is known on resulting ANS modulation and/or prevalence and significance of vagal reactions during PVI with the CB technique. We conducted a review of prevalence, putative mechanisms, and significance of VR during CB-based PVI.

  12. The vagal cardiac accelerator system in the reflex control of heart rate in conscious dogs

    NARCIS (Netherlands)

    Roossien, A; Brunsting, [No Value; Zaagsma, J; Zijlstra, WG; Muntinga, JHJ

    2000-01-01

    The reactions of the vagal cardioaccelerator (VCA) system to changes in mean arterial pressure (MAP) were studied in five beta -adrenoceptor blocked conscious dogs. An increase in MAP was obtained by administration of vasopressin or methoxamine, a decrease by doxazosin or nitroprusside. In the first

  13. Physiology and Functioning: Parents' Vagal Tone, Emotion Socialization, and Children's Emotion Knowledge

    Science.gov (United States)

    Perlman, Susan B.; Camras, Linda A.; Pelphrey, Kevin A.

    2008-01-01

    This study examined relationships among parents' physiological regulation, their emotion socialization behaviors, and their children's emotion knowledge. Parents' resting cardiac vagal tone was measured, and parents provided information regarding their socialization behaviors and family emotional expressiveness. Their 4- or 5-year-old children (N…

  14. Impact of gonadectomy on sympatho-vagal balance in male and female normotensive rat

    NARCIS (Netherlands)

    Pijacka, Wioletta; Clifford, Bethan; Walas, Dawid; Tilburgs, Chantal; Joles, Jaap A; McMullen, Sarah; Langley-Evans, Simon C

    OBJECTIVE: It is well established that autonomic nervous system and sympatho-vagal balance plays an important role in maintaining arterial blood pressure (ABP) (Salman IM., 2016) and that autonomic regulation of ABP differs between males and females (Hart EC et al., 2014). We hypothesised that sex

  15. Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

    Science.gov (United States)

    Banek, Christopher T; Knuepfer, Mark M; Foss, Jason D; Fiege, Jessica K; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W

    2016-12-01

    Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. © 2016 American Heart Association, Inc.

  16. Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats.

    Science.gov (United States)

    Behr-Roussel, Delphine; Oger, Stephanie; Caisey, Stéphanie; Sandner, Peter; Bernabé, Jacques; Alexandre, Laurent; Giuliano, Francois

    2011-02-01

    Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF). We postulated that vardenafil could improve urodynamic parameters by reducing BANF. The effect of vardenafil has been investigated on intravesical pressure by cystometry experiments while recording BANF in response to bladder filling. Complete T7-T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250-275 g). At 21-29 d postspinalization, fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Bladder afferent nerve fibers were identified by electrical stimulation of the pelvic nerve and bladder distension. SCI rats were decerebrated before cystometry experiments. Bladders were filled to determine the maximal bladder filling volume (BFV) for each rat. Then, after bladder stabilization at 75% of maximal BFV, saline (n=7) or vardenafil 1 mg/kg (n=8) was delivered intravenously. NVCs and BANF were recorded for 45 min. In all SCI rats, BANF was already present and regular at resting conditions (26.2±4.1 spikes per second). During bladder filling, intravesical pressure (IVP) slowly increased with transient NVCs superimposed. Concomitantly, BANF progressively increased up to 2.4-fold at maximal BFV (2.08±0.24 ml). After stabilization at submaximal BFV, BANF was increased by 186±37%. Vardenafil injection induced an immediate decrease in NVCs compared to saline (pdecerebrate, SCI rats. These findings provide new insights into the mechanism of action by which PDE5-Is improve storage symptoms in SCI patients. Copyright © 2010 European Association of Urology

  17. Hippocampal - brainstem connectivity associated with vagal modulation after an intense exercise intervention in healthy men

    Directory of Open Access Journals (Sweden)

    Karl Juergen Bär

    2016-04-01

    Full Text Available AbstractRegular physical exercise leads increased vagal modulation of the cardiovascular system. A combination of peripheral and central processes has been proposed to underlie this adaptation. However, specific changes in the central autonomic network have not been described in human in more detail. We hypothesized that the anterior hippocampus known to be influenced by regular physical activity might be involved in the development of increased vagal modulation after a 6 weeks high intensity intervention in young healthy men (exercise group: n=17, control group: n=17. In addition to the determination of physical capacity before and after the intervention, we used resting state functional magnetic resonance imaging and synchronic heart rate variability assessment.We detected a significant increase of the power output at the anaerobic threshold of 11.4% (p<0.001, the maximum power output Pmax of 11.2% (p<0.001, and VO2max adjusted for body weight of 4.7% (p<0.001 in the exercise group (EG. Comparing baseline (T0 and post-exercise (T1 values of parasympathetic modulation of the exercise group, we observed a trend for a decrease in heart rate (p<0.06 and a significant increase of vagal modulation as indicated by RMSSD (p<0.026 during resting state. In the whole brain analysis, we found that the connectivity pattern of the right anterior hippocampus (aHC was specifically altered to the ventromedial anterior cortex, the dorsal striatum and to the dorsal vagal complex (DVC in the brainstem. Moreover, we only observed a highly significant negative correlation between increased RMSSD after exercise and decreased functional connectivity from the right aHC to DVC (r=-0.69, p=0.003. This indicates that increased vagal modulation was associated with functional connectivity between aHC and the dorsal vagal complex.In conclusion, our findings suggest that exercise associated changes in anterior hippocampal function might be involved in increased vagal

  18. Miniature EPSPs and sensory encoding in the primary afferents of the vestibular lagena of the toadfish, Opsanus tau.

    Science.gov (United States)

    Locke, R; Vautrin, J; Highstein, S

    1999-05-28

    The synaptic activity transmitted from vestibular hair cells of the lagena to primary afferent neurons was recorded in vitro using sharp, intracellular microelectrodes. At rest, the activity was composed of miniature excitatory postsynaptic potentials (mEPSPs) at frequencies from 5 to 20/s and action potentials (APs) at frequencies betwen 0 and 10/s. mEPSPs recorded from a single fiber displayed a large variability. For mEPSPs not triggering APs, amplitudes exhibited an average coefficient of variance (CV) of 0.323 and rise times an average CV of 0.516. APs were only triggered by mEPSPs with larger amplitudes (estimated 4-6 mV) and/or steeper maximum rate of rise (10.9 mV/ms, +/- 3.7 SD, n=4 experiments) compared to (3.50 mV/ms, +/-0.07 SD, n=6 experiments) for nontriggering mEPSPs. The smallest mEPSPs showed a fast rise time (0.99 ms between 10% and 90% of peak amplitude) and limited variability across fibers (CV:0.18) confirming that they were not attenuated signals, but rather represented single-transmitter discharges (TDs). The mEPSP amplitude and rise-time relationship suggests that many mEPSPs represented several, rather than a single pulse of secretion of TDs. According to the estimated overall TD frequency, the coincidence of TDs contributing to the same mEPSP were not statistically independent, indicating a positive interaction between TDs that is reminiscent of the way subminiature signals group to form miniature signals at the neuromuscular junction. Depending on the duration and intensity of efferent stimulation, a complete block of AP initiation occurred either immediately or after a delay of a few seconds. Efferent stimulation did not significantly change AP threshold level, but abruptly decreased mEPSP frequency to a near-complete block that followed the block of APs. Maximum mEPSP rate of rise decreased during, and recovered progressively after, efferent stimulation. After termination of efferent stimulation, mEPSP amplitude did not recover

  19. Hippocampal-Brainstem Connectivity Associated with Vagal Modulation after an Intense Exercise Intervention in Healthy Men

    Science.gov (United States)

    Bär, Karl-Jürgen; Herbsleb, Marco; Schumann, Andy; de la Cruz, Feliberto; Gabriel, Holger W.; Wagner, Gerd

    2016-01-01

    Regular physical exercise leads to increased vagal modulation of the cardiovascular system. A combination of peripheral and central processes has been proposed to underlie this adaptation. However, specific changes in the central autonomic network have not been described in human in more detail. We hypothesized that the anterior hippocampus known to be influenced by regular physical activity might be involved in the development of increased vagal modulation after a 6 weeks high intensity intervention in young healthy men (exercise group: n = 17, control group: n = 17). In addition to the determination of physical capacity before and after the intervention, we used resting state functional magnetic resonance imaging and simultaneous heart rate variability assessment. We detected a significant increase of the power output at the anaerobic threshold of 11.4% (p exercise group (EG). Comparing baseline (T0) and post-exercise (T1) values of parasympathetic modulation of the exercise group, we observed a trend for a decrease in heart rate (p brain analysis, we found that the connectivity pattern of the right anterior hippocampus (aHC) was specifically altered to the ventromedial anterior cortex, the dorsal striatum and to the dorsal vagal complex (DVC) in the brainstem. Moreover, we observed a highly significant negative correlation between increased RMSSD after exercise and decreased functional connectivity from the right aHC to DVC (r = −0.69, p = 0.003). This indicates that increased vagal modulation was associated with functional connectivity between aHC and the DVC. In conclusion, our findings suggest that exercise associated changes in anterior hippocampal function might be involved in increased vagal modulation. PMID:27092046

  20. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    OpenAIRE

    Marie Hagbom; Claudia Istrate; David Engblom; Thommie Karlsson; Jesus Rodriguez-Diaz; Javier Buesa; Taylor, John A.; Vesa-Matti Loitto; Karl-Eric Magnusson; Håkan Ahlman; Ove Lundgren; Lennart Svensson

    2011-01-01

    otavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves...

  1. Effects of antidromic and orthodromic activation of STN afferent axons during DBS in Parkinson's disease: a simulation study

    Directory of Open Access Journals (Sweden)

    Guiyeom eKang

    2014-03-01

    Full Text Available Recent studies suggest that subthalamic nucleus (STN-Deep Brain Stimulation (DBS may exert at least part of its therapeutic effect through the antidromic suppression of pathological oscillations in the cortex in 6-OHDA treated rats and in PD patients. STN-DBS may also activate STN neurons by initiating action potential propagation in the orthodromic direction, similarly resulting in suppression of pathological oscillations in the STN. While experimental studies have provided strong evidence in support of antidromic stimulation of cortical neurons, it is difficult to separate relative contributions of antidromic and orthodromic effects of STN-DBS. The aim of this computational study was to examine the effects of antidromic and orthodromic activation on neural firing patterns and beta band (13-30 Hz oscillations in the STN and cortex during DBS of STN afferent axons projecting from the cortex. High frequency antidromic stimulation alone effectively suppressed simulated beta activity in both the cortex and STN-globus pallidus externa (GPe network. High frequency orthodromic stimulation, when simulated in isolation, similarly suppressed beta activity within the STN and GPe through the direct stimulation of STN neurons driven by DBS at the same frequency as the stimulus. Combined effect of antidromic and orthodromic stimulation modulated cortical activity antidromically while simultaneously orthodromically driving STN neurons. While high frequency STN-DBS reduced STN beta-band power, low frequency stimulation resulted in resonant effects, increasing beta-band activity, consistent with previous experimental observations. The simulation results indicate effective suppression of simulated oscillatory activity through both antidromic stimulation of cortical neurons and direct orthodromic stimulation of STN neurons. Results of the study agree with experimental recordings of STN and cortical neurons and support therapeutic potential for stimulation of

  2. Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in humans with and without intact vagal innervation

    DEFF Research Database (Denmark)

    Veedfald, Simon; Plamboeck, Astrid; Hartmann, Bolette

    2015-01-01

    hyperglycemia inhibits secretion. The glucose sensing mechanism has yet to be determined but may involve a vagal pathway. To investigate the role of enteral stimuli with or without intact vagal innervation, while controlling for the glucose excursion caused by the OGTT, we measured PP plasma levels by an in...... from the DPP-4i day to determine the potential effect of DPP-4-cleaved peptides on PP secretion. In both vagotomized and controls, oral glucose elicited PP secretion. In controls, but not in the vagotomized participants, intravenous glucose significantly inhibited PP secretion suggesting a vagal...

  3. Evidence from the use of vibration that the human long-latency stretch reflex depends upon spindle secondary afferents.

    Science.gov (United States)

    Matthews, P B

    1984-03-01

    The electromyographic activity of flexor pollicis longus has been recorded in normal human subjects on moving the tip of the thumb with the proximal phalanx clamped. Ramp and hold displacements (stretches) were compared with high-frequency sinusoidal movement (vibration). The subject exerted a constant flexor force between stimuli and made no voluntary response to them. On stretching the muscle by forcibly extending the thumb at various constant velocities the usual combination of short-latency (ca. 25-30 ms) and long-latency (ca. 40 ms) components of response were observed. The short-latency response progressively predominated as the velocity was increased (60-900 deg s-1, 9 deg joint displacement). One subject still showed only a long-latency response with the fastest stretch, arguing that it is a distinct reflex entity. On commencing vibration (143 Hz, 3 deg movement peak-to-peak) a short-latency response was regularly obtained, but any long-latency response was always small in relation to that elicited by stretch. This was equally so when the short-latency responses to the two types of stimulation were matched by using appropriate parameters of stimulation. The time course of the vibration response did not change appreciably with change of amplitude of vibration, so that its temporal profile was always quite different from that of the stretch response. The observed differences are in accordance with the hypothesis that the spindle group II afferents produce the long-latency excitation, with the time lost peripherally in afferent conduction rather than centrally. In relation to the strength of their Ia excitatory actions, stretch is known to excite secondary afferents more powerfully than does vibration. The findings are not readily accommodated on the hypothesis that the long-latency response is a transcortical reflex elicited by the initial Ia input, since vibration should then also have had a powerful long-latency action. Similar responses to vibration were

  4. Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans.

    Science.gov (United States)

    Di Lazzaro, V; Oliviero, A; Saturno, E; Dileone, M; Pilato, F; Nardone, R; Ranieri, F; Musumeci, G; Fiorilla, T; Tonali, P

    2005-04-15

    Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA(A) receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA(A) activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F(3,9) = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity enhancement determines a suppression of SAI and an increase of SICI.

  5. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    OpenAIRE

    Feng, Bin; La, Jun-Ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G.F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  6. Chloride is essential for contraction of afferent arterioles after agonists and potassium

    DEFF Research Database (Denmark)

    Jensen, B L; Ellekvist, Peter; Skøtt, O

    1997-01-01

    A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses...... chloride. We conclude that norepinephrine and ANG II use different mechanisms for contraction and that extracellular chloride is essential for contraction in afferent arterioles after activation of voltage-dependent calcium channels. We suggest that a chloride influx pathway is activated concomitantly...

  7. Acute physiological and electrical accentuation of vagal tone has no effect on pain or gastrointestinal motility in chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Juel J

    2017-05-01

    Full Text Available Jacob Juel,1 Christina Brock,1–4 Søren S Olesen,1,2 Adnan Madzak,5 Adam D Farmer,5–7 Qasim Aziz,7 Jens B Frøkjær,2,5 Asbjørn Mohr Drewes1,2 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, 2Department of Clinical Medicine, Aalborg University, Aalborg, 3Department of Rheumatology, Aarhus University Hospital, Aarhus, 4Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 5Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark; 6Department of Gastroenterology, University Hospitals of North Midlands, Stoke-on-Trent, 7Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK Background: The effective management of pain in chronic pancreatitis (CP remains a therapeutic challenge. Analgesic drugs, such as opioids, and the underlying pathology can impair gut function. The autonomic nervous system influences hormone secretion and gut motility. In healthy volunteers, electrical (using noninvasive transcutaneous vagal nerve stimulation [t-VNS] and physiological (using deep slow breathing [DSB] modulation of parasympathetic tone results in pain attenuation and enhanced gut motility. Thus, the aims were to investigate whether t-VNS and DSB could enhance the parasympathetic tone, decrease pain sensitivity and improve gut motility in CP.Patients and methods: A total of 20 patients (12 males, mean age=61 years, range: 50–78 years with CP were randomized to short-term (60 minutes t-VNS and DSB, or their placebo equivalent, in a crossover design. Cardiometrically derived parameters of autonomic tone, quantitative sensory testing of bone and muscle pain pressure, conditioned pain modulation (CPM and assessments of gastroduodenal motility with ultrasound were performed.Results: In comparison to sham, t-VNS and DSB increased cardiac

  8. Auditory stimulation and cardiac autonomic regulation

    Directory of Open Access Journals (Sweden)

    Vitor E. Valenti

    2012-08-01

    Full Text Available Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: "auditory stimulation", "autonomic nervous system", "music" and "heart rate variability". The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders.

  9. A comparative study of changes operated by sympathetic nervous system activation on spindle afferent discharge and on tonic vibration reflex in rabbit jaw muscles.

    Science.gov (United States)

    Passatore, M; Deriu, F; Grassi, C; Roatta, S

    1996-03-07

    The effect of sympathetic activation on the spindle afferent response to vibratory stimuli eliciting the tonic vibration reflex in jaw closing muscles was studied in precollicularly decerebrate rabbits. Stimulation of the cervical sympathetic trunk, at frequencies within the physiologic range, consistently induced a decrease in spindle response to muscle vibration, which was often preceded by a transient enhancement. Spindle discharge was usually correlated with the EMG activity in the masseter muscle and the tension reflexly developed by jaw muscles. The changes in spindle response to vibration were superimposed on variations of the basal discharge which exhibited different patterns in the studied units, increases in the firing rate being more frequently observed. These effects were mimicked by close arterial injection of the selective alpha 1-adrenoceptor agonist phenylephrine. Data presented here suggest that sympathetically-induced modifications of the tonic vibration reflex are due to changes exerted on muscle spindle afferent information.

  10. Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report

    Directory of Open Access Journals (Sweden)

    De Cicco Vincenzo

    2012-09-01

    Full Text Available Abstract Introduction A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. Case presentation A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. Conclusions A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be

  11. Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report.

    Science.gov (United States)

    De Cicco, Vincenzo

    2012-09-03

    A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be useful in patients with asymmetric hemodynamics of cerebro-afferent

  12. Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease–derived stimuli

    Science.gov (United States)

    Hockley, James R.F.; Boundouki, George; Cibert-Goton, Vincent; McGuire, Cian; Yip, Ping K.; Chan, Christopher; Tranter, Michael; Wood, John N.; Nassar, Mohammed A.; Blackshaw, L. Ashley; Aziz, Qasim; Michael, Gregory J.; Baker, Mark D.; Winchester, Wendy J.; Knowles, Charles H.; Bulmer, David C.

    2014-01-01

    Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitization of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9−/− mice. Deletion of NaV1.9 substantially attenuates excitation and subsequent mechanical hypersensitivity after application of inflammatory soup (IS) (bradykinin, ATP, histamine, PGE2, and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9, and there was a rightward shift in stimulus–response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however, run-down of responses to repeat phasic distension were exacerbated in NaV1.9−/− afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9−/− mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics. PMID:24972070

  13. Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease-derived stimuli.

    Science.gov (United States)

    Hockley, James R F; Boundouki, George; Cibert-Goton, Vincent; McGuire, Cian; Yip, Ping K; Chan, Christopher; Tranter, Michael; Wood, John N; Nassar, Mohammed A; Blackshaw, L Ashley; Aziz, Qasim; Michael, Gregory J; Baker, Mark D; Winchester, Wendy J; Knowles, Charles H; Bulmer, David C

    2014-10-01

    Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitization of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9(-/-) mice. Deletion of NaV1.9 substantially attenuates excitation and subsequent mechanical hypersensitivity after application of inflammatory soup (IS) (bradykinin, ATP, histamine, PGE2, and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9, and there was a rightward shift in stimulus-response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however, run-down of responses to repeat phasic distension were exacerbated in NaV1.9(-/-) afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9(-/-) mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  14. Topographical features of the vagal nerve at the cervical level in an aging population evaluated by ultrasound

    Directory of Open Access Journals (Sweden)

    Akinori Inamura, MD

    2017-09-01

    Conclusion: Our study encourages utilizing longitudinal and cross-individual ultrasound studies within and amongst individuals of different ages to allow understanding the variations of the vagal nerve in its neck portion. This has implications to many neurosurgical procedures.

  15. Imaging stretch-activated firing of spinal afferent nerve endings in mouse colon

    Directory of Open Access Journals (Sweden)

    Lee etravis

    2013-10-01

    Full Text Available Spinal afferent neurons play a major role in detecting noxious and innocuous stimuli from visceral organs, such as the gastrointestinal tract. However, all our understanding about spinal afferents has been obtained from recordings of spinal afferent axons, or cell bodies that lie outside the gut wall, or peripheral organ they innervate. No recordings have been made directly from spinal afferent nerve endings, which is where sensory transduction occurs. We developed a preparation whereby recordings could be made from rectal afferent nerve endings in the colon, to characterize mechanisms underlying sensory transduction. Dorsal root ganglia (L6-S2 were removed from mice, whilst retaining neural continuity with the colon. Fluo-4-AM was used to record from rectal afferent nerve endings in myenteric ganglia and circular muscle at 36oC. In slack (unstretched preparations of colon, no calcium transients were recorded from spinal afferent endings. However, in response to a maintained increase in circumferential diameter, a maintained discharge of calcium transients occurred simultaneously in multiple discrete varicosities along single axons of rectal afferents in myenteric ganglia and circular muscle. Stretch-activated calcium transients were resistant to hexamethonium and nifedipine, but were abolished by tetrodotoxin, CPA, BAPTA-AM, cobalt, gadolinium, or replacement of extracellular Na+ with NMDG. In summary, we present a novel preparation in which stretch-activated firing of spinal afferent nerve endings can be recorded, using calcium imaging. We show that circumferential stretch of the colon activates a maintained discharge of calcium transients simultaneously in varicosities along single rectal afferent endings in myenteric ganglia and circular muscle. Non-selective cation channels, TTX-sensitive Na+ channels and both extracellular calcium influx and intracellular Ca2+ stores are required for stretch-activated calcium transients in rectal afferent

  16. Nociceptive afferents selectively modulate the cardiac component of the peripheral chemoreceptor reflex via actions within the solitary tract nucleus.

    Science.gov (United States)

    Boscan, P; Paton, J F R

    2002-01-01

    Our previous findings showed that the nucleus of the solitary tract (NTS) mediated part of the tachycardia evoked during somatic noxious stimulation. Here, we investigated the interaction between somatic nociceptor- and peripheral chemoreceptor-evoked cardiac changes. We sought to determine whether this interaction occurred within the NTS, the primary site of termination of chemoreceptor afferents. In a working heart-brainstem preparation of rat, mechanical noxious activation of a forelimb evoked a tachycardia of 17.5+/-3 (mean+/-S.E.M.) b.p.m., whereas sodium cyanide (7-30 microg) stimulation of peripheral chemoreceptors produced a sub-maximal bradycardia of -140+/-15 b.p.m. During nociceptor stimulation the sodium cyanide-evoked bradycardia was attenuated to -42.6+/-12 b.p.m. but could be prevented by a multiple bilateral NTS microinjection of bicuculline (i.e. -173+/-18 b.p.m.). Furthermore, the activity of NTS neurones responding to peripheral chemoreceptor stimulation increased from 2.8+/-1.3 to 9.4+/-1.9 Hz during sodium cyanide injection (n=7; Pchemoreceptor-evoked excitatory synaptic response. We conclude that somatic noxious stimulation attenuates the chemoreceptor reflex-evoked bradycardia via a GABA(A)ergic mechanism in the NTS.

  17. Interactions between visceral afferent signaling and stimulus processing

    Directory of Open Access Journals (Sweden)

    Hugo D Critchley

    2015-08-01

    Full Text Available Visceral afferent signals to the brain influence thoughts, feelings and behaviour. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body, to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated physiological arousal to emotional, social and motivational behaviours, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain’s representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed.

  18. Anatomy and physiology of the afferent visual system.

    Science.gov (United States)

    Prasad, Sashank; Galetta, Steven L

    2011-01-01

    The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Vagal Tone and Children���s Delay of Gratification: Differential Sensitivity Across Resource Poor and Resource Rich Environments

    OpenAIRE

    Sturge-Apple, Melissa L.; Suor, Jennifer H.; Davies, Patrick T.; Cicchetti, Dante; Skibo, Michael A.; Rogosch, Fred A.

    2016-01-01

    Socioeconomic disparities in children���s delay of gratification exist, with impoverished children displaying greater difficulties in this developmental domain. The present paper examined the role of vagal tone in predicting the ability to delay gratification across resource rich and resource poor environments. Embedding hypotheses within evolutionary models of children���s conditional adaptation to proximal rearing contexts, Study 1 tested whether elevated vagal tone was associated with lowe...

  20. Vagal changes following cancer chemotherapy: implications for the development of nausea.

    Science.gov (United States)

    Morrow, G R; Andrews, P L; Hickok, J T; Stern, R

    2000-05-01

    Many physiological changes that occur contemporaneously with nausea are mediated by the autonomic nervous system, but the specific autonomic changes associated with nausea have not been characterized. Cardiac parasympathetic (vagal) activity as indicated by heart rate variability, measured as the standard deviation of successive differences (SDSD) in beat-to-beat intervals, was assessed in 24 women with ovarian cancer immediately prior to and accompanying nausea that occurred following anticancer chemotherapy. A progressive increase in SDSD followed infusion of the chemotherapy agent, indicating a rise in cardiac parasympathetic (vagal) activity, with onset of nausea consistently occurring after the peak activity had been reached, at a time when SDSD was decreasing. An increase in parasympathetic activity seems to set the stage for the expression of nausea but an additional stimulus is apparently needed to finally trigger the event.

  1. High-intensity interval exercise improves vagal tone and decreases arrhythmias in chronic heart failure.

    Science.gov (United States)

    Guiraud, Thibaut; Labrunee, Marc; Gaucher-Cazalis, Kevin; Despas, Fabien; Meyer, Philippe; Bosquet, Laurent; Gales, Celine; Vaccaro, Angelica; Bousquet, Marc; Galinier, Michel; Sénard, Jean-Michel; Pathak, Atul

    2013-10-01

    Autonomic dysfunction including sympathetic activation and vagal withdrawal has been reported in patients with chronic heart failure (CHF). We tested the hypotheses that high-intensity interval exercise (HIIE) in CHF patients would enhance vagal modulation and thus decrease arrhythmic events. Eighteen CHF patients underwent a baseline assessment (CON) and were then randomized to a single session of HIIE and to an isocaloric moderate-intensity continuous exercise (MICE). We evaluated the HR, HR variability parameters, and arrhythmic events by 24-h Holter ECG recordings after HIIE, MICE, and CON sessions. We found that HR was significantly decreased after HIIE (68 ± 3 bpm, P CHF patients, leading to significant reductions of HR and arrhythmic events in a 24-h posttraining period. Cardioprotective effects of HIIE in CHF patients need to be confirmed in a larger study population and on a long-term basis.

  2. Perturbed sympatho-vagal balance in Turner syndrome - relation to aortic dilation

    DEFF Research Database (Denmark)

    Trolle, Christian; Mortensen, Kristian Havmand; Andersen, Niels Holmark

    examined once. Aortic dimensions were measured at nine positions using 3D, non-contrast and free-breathing cardiovascular-MRI. HRV measured by short-term spectral analysis (supine-standing), transthoracic echocardiography, 24-hour ambulatory BP were done. Results: The changes in High frequency (HF) power......-average=-0.312 and -0.341; pmeasures of HRV. Prospectively there were no changes in HRV. Conclusions: A perturbed sympatho-vagal balance is present in TS explained by a decreased vagal activity......Objective: The risk of aortic dissection is 100 fold increased in Turner syndrome (TS). Increased blood pressure (BP) and heart rate is present as well as an increased risk of ischemic heart disease and diabetes. This study aimed to prospectively assess heart rate variability (HRV) in TS and its...

  3. Stressing the feedback: attention and cardiac vagal tone during a cognitive stress task.

    Science.gov (United States)

    Azam, Muhammad Abid; Ritvo, Paul; Fashler, Samantha R; Katz, Joel

    2017-07-07

    The present study examined relationships among gaze behaviour and cardiac vagal tone using a novel stress-inducing task. Participants' (N = 40) eye movements and heart rate variability (HRV) were measured during an unsolvable computer-based task randomly presenting feedback of "Right" and "Wrong" answers distinctly onscreen after each trial. Subgroups were created on the basis of more frequent eye movements to the right ("Correct"-Attenders; n = 23) or wrong ("Incorrect"-Attenders; n = 17) areas onscreen. Correct-Attenders maintained HRV from baseline to the stress task. In contrast, Incorrect-Attenders spent significantly more time viewing "Wrong" feedback, exhibited a reduction in HRV during the stress condition (p attention to negative feedback ("Wrong") elicits perseverative stress and negative self-evaluations among university students. This study highlights the potential for studying attentional biases and emotional distress through combined measures of gaze behaviour and cardiac vagal tone.

  4. Parenting behaviors and vagal tone at six months predict attachment disorganization at twelve months.

    Science.gov (United States)

    Holochwost, Steven J; Gariépy, Jean-Louis; Propper, Cathi B; Mills-Koonce, W Roger; Moore, Ginger A

    2014-09-01

    The authors investigated the relationships among parenting behaviors, infant vagal tone, and subsequent attachment classification. Vagal tone was assessed among 6-month olds (n = 95) during the still-face paradigm (SFP) via respiratory sinus arrhythmia (RSA), while attachment security and disorganization were measured at 12 months during the strange situation procedure (SSP). Infants demonstrating higher levels of RSA during the normal interaction and reunion episodes of the SFP whose mothers were also rated as negative-intrusive exhibited higher levels of attachment disorganization at 12 months, while infants with lower RSA and mothers who were negative-intrusive did not exhibit higher levels of disorganization. These results suggest that high levels of RSA may not be adaptive within the context of negative-intrusive parenting. © 2014 Wiley Periodicals, Inc.

  5. Cardiac vagal reactivity during relived sadness is predicted by affect intensity and emotional intelligence.

    Science.gov (United States)

    Rash, Joshua A; Prkachin, Kenneth M

    2013-02-01

    The induction of one particular emotion - sadness - has shown two different profiles of autonomic nervous system (ANS) response that are characterized by activation, or withdrawal in cardiac parasympathetic activation. We tested whether individual differences in emotion expression predict cardiac vagal reactivity from baseline to autobiographical sadness induction. Respiration sinus arrhythmia (RSA(c)) was measured in 56 adults (28 men) asked to relive an episode of sadness. Participants completed an emotional intelligence (EI) test, and a measure of trait affect intensity. Sadness resulted in cardiac vagal activation with concomitant increase in HR suggestive of parasympathetic and sympathetic co-activation. Individual differences were observed in autonomic reactivity during sadness. Higher scores on the affect intensity measure and the emotional intelligence test predicted greater change in RSA(c) during sadness and recovery. The tendency to experience affect intensely and the ability to perceive emotions predict adaptive physiological regulation during sadness. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Vagal denervation inhibits the increase in pulmonary blood flow during partial lung aeration at birth.

    Science.gov (United States)

    Lang, Justin A R; Pearson, James T; Binder-Heschl, Corinna; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; Te Pas, Arjan B; Lewis, Robert A; Polglase, Graeme R; Shirai, Mikiyasu; Hooper, Stuart B

    2017-03-01

    Lung aeration at birth significantly increases pulmonary blood flow, which is unrelated to increased oxygenation or other spatial relationships that match ventilation to perfusion. Using simultaneous X-ray imaging and angiography in near-term rabbits, we investigated the relative contributions of the vagus nerve and oxygenation to the increase in pulmonary blood flow at birth. Vagal denervation inhibited the global increase in pulmonary blood flow induced by partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect. The results of the present study indicate that a vagal reflex may mediate a rapid global increase in pulmonary blood flow in response to partial lung aeration. Air entry into the lungs at birth triggers major cardiovascular changes, including a large increase in pulmonary blood flow (PBF) that is not spatially related to regional lung aeration. To investigate the possible underlying role of a vagally-mediated stimulus, we used simultaneous phase-contrast X-ray imaging and angiography in near-term (30 days of gestation) vagotomized (n = 15) or sham-operated (n = 15) rabbit kittens. Rabbits were imaged before ventilation, when one lung was ventilated (unilateral) with 100% nitrogen (N2 ), air or 100% oxygen (O2 ), and after all kittens were switched to unilateral ventilation in air and then ventilation of both lungs using air. Compared to control kittens, vagotomized kittens had little or no increase in PBF in both lungs following unilateral ventilation when ventilation occurred with 100% N2 or with air. However, relative PBF did increase in vagotomized animals ventilated with 100% O2 , indicating the independent stimulatory effects of local oxygen concentration and autonomic innervation on the changes in PBF at birth. These findings demonstrate that vagal denervation inhibits the previously observed increase in PBF with partial lung aeration, although high inspired oxygen concentrations can partially

  7. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.

    Science.gov (United States)

    Bercik, P; Park, A J; Sinclair, D; Khoshdel, A; Lu, J; Huang, X; Deng, Y; Blennerhassett, P A; Fahnestock, M; Moine, D; Berger, B; Huizinga, J D; Kunze, W; McLean, P G; Bergonzelli, G E; Collins, S M; Verdu, E F

    2011-12-01

    The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system. © 2011 Blackwell Publishing Ltd.

  8. Working Memory Load Under Anxiety: Quadratic Relations to Cardiac Vagal Control and Inhibition of Distractor Interference

    OpenAIRE

    Spangler, Derek P

    2016-01-01

    Anxiety is marked by impaired inhibition of distraction (Eysenck et al., 2007). It is unclear whether these impairments are reduced or exacerbated when loading working memory (WM) with non-affective information. Cardiac vagal control has been related to emotion regulation and may serve as a proxy for load-related inhibition under anxiety (Thayer and Lane, 2009). The present study examined whether: (1) the enhancing and impairing effects of load on inhibition exist together in a nonlinear func...

  9. Neural correlates of heterotopic facilitation induced after high frequency electrical stimulation of nociceptive pathways

    NARCIS (Netherlands)

    Broeke, E.N. van den; Heck, C.H. van; Rijn, C.M. van; Wilder-Smith, O.H.G.

    2011-01-01

    Background High frequency electrical stimulation (HFS) of primary nociceptive afferents in humans induce a heightened sensitivity in the surrounding non-stimulated skin area. Several studies suggest that this heterotopic effect is the result of central (spinal) plasticity. The aim of this study is

  10. Neural correlates of heterotopic facilitation induced after high frequency electrical stimulation of nociceptive pathways

    NARCIS (Netherlands)

    Broeke, E.N. van den; Heck, C.H. van; Rijn, C.M. van; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND: High frequency electrical stimulation (HFS) of primary nociceptive afferents in humans induce a heightened sensitivity in the surrounding non-stimulated skin area. Several studies suggest that this heterotopic effect is the result of central (spinal) plasticity. The aim of this study is

  11. Development of fusimotor innervation correlates with group Ia afferents but is independent of neurotrophin-3

    NARCIS (Netherlands)

    Ringstedt, T; Copray, S; Walro, J; Kucera, J

    1998-01-01

    Fusimotor neurons, group Ia afferents and muscle spindles are absent in mutant mice lacking the gene for neurotrophin-3 (NT3). To partition the effect of Ia afferent or spindle absence from that of NT3 deprivation on fusimotor neuron development, we examined the fusimotor system in a mutant mouse

  12. Effect of nicotine on the pelvic afferent nerve activity and bladder pressure in rats.

    Science.gov (United States)

    Kontani, Hitoshi; Okamura, Takashi; Kimura, Satoko; Ishida, Kazuumi; Takeno, Satoshi

    2009-08-01

    To record afferent nerve activity and bladder pressure in anesthetized male rats and to investigate whether increased afferent nerve activity induced by nicotine is able to evoke reflex bladder contractions. Using continuous infusion cystometrography, bladder pressure was measured via a bladder cannula. Afferent activity was recorded in the uncut L6 dorsal root. Nicotine was injected intra-arterially through a cannula placed near the bifurcation of the internal iliac artery a few minutes after micturition. Nicotine (0.15-1.5 micromol) evoked a marked elevation of afferent discharge without a simultaneous increase in bladder pressure. Bladder contractions appeared about 43 and 19 s after bolus injection of nicotine at 0.45 and 1.5 micromol, respectively. Firing rates of afferent nerves were reduced when the contraction appeared. Continuous infusion of nicotine at 0.75 micromol/min for 20 min evoked marked elevation of afferent discharge, which was maintained during infusion of nicotine and after it had been withdrawn. Repetitive contractions were observed thereafter and disappeared when the L6 dorsal roots were bilaterally resected. A transient increase in afferent discharges induced by bolus injection of nicotine was unable to evoke reflex bladder contraction. Repetitive bladder contractions after withdrawal of continuous nicotine infusion were induced in a reflex manner by the increased afferent activity.

  13. Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn

    DEFF Research Database (Denmark)

    Fernández, A; Radmilovich, M; Russo, R E

    1996-01-01

    This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have re...

  14. Total Reconstruction of the Afferent Loop for Treatment of Radiation-Induced Afferent Loop Obstruction with Segmental Involvement after Pancreaticoduodenectomy with Roux-en-Y Reconstruction

    Directory of Open Access Journals (Sweden)

    Konstantinos Blouhos

    2013-08-01

    Full Text Available As the literature on afferent loop obstruction (ALO after pancreaticoduodenectomy (PD is very limited, standardized rules for its management do not exist. Herein, we report the case of a 65-year-old male patient with chronic ALO who had undergone PD with single Roux-en-Y limb reconstruction and adjuvant chemoradiation therapy for pancreatic head adenocarcinoma 2 years earlier. The patient was brought to the operating room with the diagnosis of radiation enteritis of the afferent loop with segmental involvement and concurrent hepaticojejunostomy (HJ and pancreaticojejunostomy (PJ stricture. Complete mobilization of the afferent loop, removal of the affected segment and reconstruction were performed. Reconstruction of the afferent loop was a one-way option for the surgeons because the Roux-en-Y reconstruction limited endoscopic access to the afferent loop, and the segmental radiation injury of the afferent loop ruled out bypass surgery. However, mobilization of the affected segment through a field of dense adhesions and revision of the HJ and PJ were technically demanding.

  15. Heart rate variability predicts levels of inflammatory markers: Evidence for the vagal anti-inflammatory pathway.

    Science.gov (United States)

    Cooper, Timothy M; McKinley, Paula S; Seeman, Teresa E; Choo, Tse-Hwei; Lee, Seonjoo; Sloan, Richard P

    2015-10-01

    Evidence from numerous animal models shows that vagal activity regulates inflammatory responses by decreasing cytokine release. Heart rate variability (HRV) is a reliable index of cardiac vagal regulation and should be inversely related to levels of inflammatory markers. Inflammation is also regulated by sympathetic inputs, but only one previous paper controlled for this. In a larger and more representative sample, we sought to replicate those results and examine potential sex differences in the relationship between HRV and inflammatory markers. Using data from the MIDUS II study, we analyzed the relationship between 6 inflammatory markers and both HF-HRV and LF-HRV. After controlling for sympathetic effects measured by urinary norepinephrine as well as a host of other factors, LF-HRV was found to be inversely associated with fibrinogen, CRP and IL-6, while HF-HRV was inversely associated with fibrinogen and CRP. We did not observe consistent sex differences. These results support the existence of the vagal anti-inflammatory pathway and suggest that it has similar effects in men and women. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Vagal Paraganglioma Presenting as a Neck Mass Associated with Cough on Palpation

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    Richard Heyes

    2017-01-01

    Full Text Available A 70-year-old female presented with a neck mass and sporadic dry cough, often leading to fits of coughing severe enough to cause vomiting. The patient reported that touching the mass triggered the cough. On examination, a 2.5 cm right-sided level two neck mass deep to the sternocleidomastoid was present. Palpation of the mass immediately triggered coughing. Cross-sectional imaging proposed vagal paraganglioma as the chief differential, which was confirmed following surgical excision. The patient reported complete resolution of her severe dry cough after surgery. Vagal paragangliomas are rare neuroendocrine tumors arising from the neural crest-derived paraganglionic tissue surrounding the vagus nerve, typically presenting as a neck mass associated with hoarseness or pulsatile tinnitus. To the best of our knowledge this is a unique description in the English literature. This case is presented to aid physicians should they encounter a neck mass associated with cough. Vagal paraganglioma, although rare, should be part of the differential in such a presentation.

  17. Cardiac vagal tone, a non-invasive measure of parasympathetic tone, is a clinically relevant tool in Type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Brock, C; Jessen, N. C.; Brock, Birgitte

    2017-01-01

    in people with Type 1 diabetes than in a matched healthy cohort and lower still in people with established neuropathy. METHODS: Cardiac vagal tone is a validated cardiometrically derived index of parasympathetic tone. It is measured using a standard three-lead electrocardiogram which connects, via Bluetooth......, to a smartphone application. A 5-min resting recording of cardiac vagal tone was undertaken and observational comparisons were made between 42 people with Type 1 diabetes and peripheral neuropathy and 23 without peripheral neuropathy and 65 healthy people. In those with neuropathy, 24-h heart rate variability...... values were compared with cardiac vagal tone. Correlations between cardiac vagal tone and clinical variables were also made. RESULTS: Cardiac vagal tone was lower in people with established neuropathy and Type 1 diabetes in comparison with healthy participants [median (interquartile range) linear vagal...

  18. Release of prostaglandin E2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans

    DEFF Research Database (Denmark)

    Madsen, Jørgen Rask; Bukhave, K; Hovendal, C P

    1981-01-01

    .2-18 ng/Meq H+). The findings are consistent with the hypothesis that activation of muscarinic receptors represents the physiologic mechanism by which gastric release of PGs is regulated. Cyclic variations in gastric PG formation appear to occur in response to vagal stimulation since the peaks in PGE2...

  19. Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

    Science.gov (United States)

    Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

    2011-10-01

    The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

  20. CELIOMESENTERIC AFFERENCE OF THE DORSOLUMBAR NEUROMERS IN HORSE

    Directory of Open Access Journals (Sweden)

    CARMEN BERGHES

    2008-05-01

    Full Text Available The frequent variability of the splanchnic branches in all species creates difficulties both in carrying out physiological experiments and, particularly, in some specifications concerning the neuroglandular relations in the mesenteric area in horses. A total of 32 dissections were conducted on fresh, non-mummified corpses and were accompanied by comparative evaluations. The nervous formations were tracked up to the limit of visibility with the magnifying glass of 15 dioptres. To make possible the differentiation of the nervous fibres, the arteries were injected with a red dye. The ganglion formations were investigated with histological methods of differentiation. The dissection also revealed that the efferent fibres which approach the celiomesenteric plexus do not belong, as thought, only to the large and small splanchnic, but also to the lumbar splanchnic nerves which were regarded as being small accessory splanchnic nerves. According to these wrong data, the renosuprarenal plexus would only include abdominal splanchnic afferences and not also lumbar splanchnic afferences, as it actually happens. Speaking of horses, the data reveal the existence of peculiarities regarding the dorsolumbar efferences of the celiomesenteric plexus which detach in most cases from the interganglionar connectives and not directly from the paravertebral ganglia. Another observation is related to the existence of the renal nerves (one or two small fibres, nerves which detach from the abdominal splanchnic nerves which, crossing over the lateral side of the suprarenal gland seem to link it to the kidneys. The existence of postrenal nervous loops might provide evidence, if not on the ontogeny, at least on the way of postembryonic migration of this organ.

  1. Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents

    Directory of Open Access Journals (Sweden)

    Inoue Makoto

    2007-12-01

    Full Text Available Abstract Background We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized. Results Here, we show that choline acetyltransferase (ChAT signals were localized not only in outer dorsal horn fibers (lamina I–III and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG. When mice were treated with an antisense oligodeoxynucleotide (AS-ODN against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW test, the thresholds for stimulation through C-, Aδ- and Aβ-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t. induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS-ODN in all of these nociception tests. Conclusion These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition.

  2. Sensory sciatic nerve afferent inputs to the dorsal lateral medulla in the rat.

    Science.gov (United States)

    Alioto, Olavo Egídio; Lindsey, Charles Julian; Koepp, Janice; Caous, Cristofer André

    2008-06-01

    Investigations show the paratrigeminal nucleus (Pa5) as an input site for sensory information from the sciatic nerve field. Functional or physical disruption of the Pa5 alters behavioral and somatosensory responses to nociceptive hindpaw stimulation or sciatic nerve electrostimulation (SNS), both contralateral to the affected structure. The nucleus, an input site for cranial and spinal nerves, known for orofacial nociceptive sensory processing, has efferent connections to structures associated with nociception and cardiorespiratory functions. This study aimed at determining the afferent sciatic pathway to dorsal lateral medulla by means of a neuronal tract-tracer (biocytin) injected in the iliac segment of the sciatic nerve. Spinal cord samples revealed bilateral labeling in the gracile and pyramidal or cuneate tracts from survival day 2 (lumbar L1/L2) to day 8 (cervical C2/C3 segments) following biocytin application. From day 10 to day 20 medulla samples showed labeling of the contralateral Pa5 to the injection site. The ipsilateral paratrigeminal nucleus showed labeling on day 10 only. The lateral reticular nucleus (LRt) showed fluorescent labeled terminal fibers on day 12 and 14, after tracer injection to contralateral sciatic nerve. Neurotracer injection into the LRt of sciatic nerve-biocytin-treated rats produced retrograde labeled neurons soma in the Pa5 in the vicinity of biocytin labeled nerve terminals. Therefore, Pa5 may be considered one of the first sites in the brain for sensory/nociceptive inputs from the sciatic nerve. Also, the findings include Pa5 and LRt in the neural pathway of the somatosympathetic pressor response to SNS and nocifensive responses to hindpaw stimulation.

  3. Heterogeneity and dynamics of lateral line afferent innervation during development in zebrafish (Danio rerio).

    Science.gov (United States)

    Haehnel, Melanie; Taguchi, Masashige; Liao, James C

    2012-05-01

    The lateral line system of larval zebrafish is emerging as a model to study a range of topics in neurobiology, from hair cell regeneration to sensory processing. However, despite numerous studies detailing the patterning and development of lateral line neuromasts, little is known about the organization of their connections to afferent neurons and targets in the hindbrain. We found that as fish grow and neuromasts proliferate over the body surface, the number of afferent neurons increases linearly. The number of afferents innervating certain neuromasts increases over time, while it decreases for other neuromasts. The ratio of afferent neurons to neuromasts differs between the anterior and posterior lateral line system, suggesting potential differences in sensitivity threshold or spatial resolution. A single afferent neuron routinely contacts a group of neuromasts, suggesting that different afferent neurons can convey information about receptive fields along the body. When afferent projections are traced into the hindbrain, where a distinct somatotopy has been previously described, we find that this general organization is absent at the Mauthner cell. We speculate that directional input from the lateral line is less important at an early age, whereas the speed of the escape response is paramount, and that directional responses arise later in development. By quantifying morphological connections in the lateral line system, this study provides a detailed foundation to understand how hydrodynamic information is processed and ultimately translated into appropriate motor behaviors. Copyright © 2011 Wiley Periodicals, Inc.

  4. Neurophysiological changes in the afferent somatosensory system indices in the case of vertebrogenic spine pathology in miners

    Directory of Open Access Journals (Sweden)

    Sharbanu Battakova

    2013-04-01

    Full Text Available Objectives: The aim of the paper was to prove that job conditions impact the state of the afferent part of the somatosensory system in miners. Materials and Methods: Data analysis of the electrophysiological examination of the syndrome in 148 patients, aged from 28 to 55 years, with a mild, moderate and severe degree of the pain syndrome was performed. The control group included 28 people without any pain symptoms. The method used was that of somatosensory stimulated potential (SSP with the potentials amplitude and latency main components taken into consideration. Results: It was proven that the true decrease of the somatosensory stimulated potential SSP N22 (p < 0.05 component amplitudes by 41%; N30 component amplitude tend to decrease by 26%. This proves that the true N22 (p < 0.01 component latency increase by 63.8% corresponds to afferent excitation wave conductibility under the pain syndrome of vertebral pathology through sensitivity pathways mainly in the posterior spinal cord columns and then, through the parts of the brain stem, involving the cerebral cortex, which is confirmed by the fact that the P38 and P46 components amplitudes tend to decrease. In addition to this, the proven N10–N13 (p < 0.05, N13–N20 (p < 0.05, N10–N20 (p < 0.05 intervals increases by 43.5–41.8–38.7%, respectively, correspond to the nervous impulse conductibility through the peripheral nervous system structures and allow to reveal the subclinical slowdown of impulse conductibility, which indicates that the conducting system is changed even under a mild pain syndrome. Conclusions: It was found that the data obtained allow for the better understanding of how the neuropathological pain syndrome under vertebral spine pathology is formed.

  5. Changes in gustatory perceptions of patients with major depression treated with vagus nerve stimulation (VNS).

    Science.gov (United States)

    Sperling, W; Biermann, T; Spannenberger, R; Clepce, M; Padberg, F; Reulbach, U; Kornhuber, J; Thuerauf, N

    2011-03-01

    Olfactory and gustatory functions were investigated before and during vagus nerve stimulation (VNS) in a group of 9 patients with therapy-resistant depression, implanted with a VNS system. Gustation and olfaction were tested using standard sniffing tests. Subjects participated in 2 sessions with the vagal stimulator switched on and off, respectively. Under conditions of stimulation of the VNS, there were statistically significant differences of the threshold of perception, with an intensification of the taste "sweet" (Z = -2.0; p = 0.048) and "bitter" (Z = - 2.5; p = 0.011) compared to the "off-mode". A statistical trend (Z = - 1.7; p=0.098) for increased intensity of the taste "salty" was observed, however, these results would supposedly disappear after correction for multiple testing presumably due to the large number of variables and the small sample size. There were no statistically relevant differences concerning olfactory perception. The changes of gustatory perception under conditions of vagal nerve stimulation observed in this study show another important central nervous effect of vagal stimulation on the limbic system that might be of importance in the elucidation of mechanisms of action of VNS especially on refractory depression. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Sonia Pellissier

    Full Text Available Crohn's disease (CD and irritable bowel syndrome (IBS involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls. The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients. The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI and depressive symptoms (CES-D. After 30 min of rest, ECG was recorded for heart rate variability (HRV analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05 was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05. No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

  7. Opioid Actions in Primary-Afferent Fibers—Involvement in Analgesia and Anesthesia

    Directory of Open Access Journals (Sweden)

    Tsugumi Fujita

    2011-01-01

    Full Text Available Opioids inhibit glutamatergic excitatory transmission from the periphery by activating G-protein coupled opioid receptors in the central terminals of primary-afferent neurons in the spinal substantia gelatinosa, resulting in antinociception. Opioid receptor activation in the peripheral terminals of primary-afferent neurons inhibits the production of action potentials in response to nociceptive stimuli given to the periphery, leading to antinociception. Opioids also exhibit a local anesthetic effect without opioid receptor activation in peripheral nerve fibers. This review article will focus on analgesia and anesthesia produced by the actions of opioids on primary-afferent fibers.

  8. Percutaneous jejunostomy through the liver parenchyma for palliation of afferent loop syndrome.

    Science.gov (United States)

    Kwon, Jae Hyun; Han, Yoon Hee

    2015-01-01

    In the treatment of afferent loop syndrome, jejunostomy or Roux-en-Y gastrojejunostomy have tended to represent the preferred procedures. In patients who are not good candidates for surgery, palliative treatment-i.e., percutaneous transhepatic biliary drainage or percutaneous direct transperitoneal jejunostomy techniques-have been applied. Transhepatic biliary drainage confers a risk of ascending cholangitis. Direct percutaneous transperitoneal drainage may be impractical when overlying bowel loops prevent access to deeply located afferent loops. In the present case, percutaneous jejunostomy through the liver parenchyma was performed successfully for palliation of afferent loop syndrome.

  9. Vagal Tone and Children's Delay of Gratification: Differential Sensitivity in Resource-Poor and Resource-Rich Environments.

    Science.gov (United States)

    Sturge-Apple, Melissa L; Suor, Jennifer H; Davies, Patrick T; Cicchetti, Dante; Skibo, Michael A; Rogosch, Fred A

    2016-06-01

    Children from different socioeconomic backgrounds have differing abilities to delay gratification, and impoverished children have the greatest difficulties in doing so. In the present study, we examined the role of vagal tone in predicting the ability to delay gratification in both resource-rich and resource-poor environments. We derived hypotheses from evolutionary models of children's conditional adaptation to proximal rearing contexts. In Study 1, we tested whether elevated vagal tone was associated with shorter delay of gratification in impoverished children. In Study 2, we compared the relative role of vagal tone across two groups of children, one that had experienced greater impoverishment and one that was relatively middle-class. Results indicated that in resource-rich environments, higher vagal tone was associated with longer delay of gratification. In contrast, high vagal tone in children living in resource-poor environments was associated with reduced delay of gratification. We interpret the results with an eye to evolutionary-developmental models of the function of children's stress-response system and adaptive behavior across varying contexts of economic risk. © The Author(s) 2016.

  10. Vagal Tone and Children’s Delay of Gratification: Differential Sensitivity Across Resource Poor and Resource Rich Environments

    Science.gov (United States)

    Sturge-Apple, Melissa L.; Suor, Jennifer H.; Davies, Patrick T.; Cicchetti, Dante; Skibo, Michael A.; Rogosch, Fred A.

    2016-01-01

    Socioeconomic disparities in children’s delay of gratification exist, with impoverished children displaying greater difficulties in this developmental domain. The present paper examined the role of vagal tone in predicting the ability to delay gratification across resource rich and resource poor environments. Embedding hypotheses within evolutionary models of children’s conditional adaptation to proximal rearing contexts, Study 1 tested whether elevated vagal tone was associated with lower delay of gratification within impoverished children. Study 2 compared the relative role of vagal tone across two groups of children, one which experienced greater impoverishment and one which was relatively middle-class. Results indicated that within resource rich environments, high vagal tone was associated with greater delay of gratification. In contrast, high vagal tone in children living within resource poor environments was associated with reduced delay of gratification. The results are interpreted within evolutionary-developmental models of children’s stress response system functioning and adaptive behavior across varying contexts of economic risk. PMID:27117276

  11. Mothers’ Responses to Children’s Negative Emotions and Child Emotion Regulation: The Moderating Role of Vagal Suppression

    Science.gov (United States)

    Perry, Nicole B.; Calkins, Susan D.; Nelson, Jackie A.; Leerkes, Esther M.; Marcovitch, Stuart

    2011-01-01

    The current study examined the moderating effect of children’s cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and non-supportive responses) and children’s emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children’s negative emotions and children’s regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children’s vagal suppression moderated the association between mothers’ non-supportive emotion socialization and children’s emotion regulation behaviors such that non-supportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children’s emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against non-supportive emotion socialization. PMID:22072217

  12. Non-intubated thoracoscopic surgery using internal intercostal nerve block, vagal block and targeted sedation.

    Science.gov (United States)

    Hung, Ming-Hui; Hsu, Hsao-Hsun; Chan, Kuang-Cheng; Chen, Ke-Cheng; Yie, Jr-Chi; Cheng, Ya-Jung; Chen, Jin-Shing

    2014-10-01

    Thoracoscopic surgery using internal intercostal nerve block, vagal block and targeted sedation without endotracheal intubation is a promising technique for selected patients, but little is known about its feasibility and safety. We evaluated 109 patients with lung (105), mediastinal (3) or pleural (1) tumours treated using non-intubated thoracoscopic surgery. Internal, intercostal nerve block was performed at the T3-T8 intercostal level and vagal block was performed adjacent to the vagus nerve at the level of the lower trachea for right-sided operations and at the level of the aortopulmonary window for left-sided operations. Sedation was performed with propofol infusion to achieve a bispectral index value between 40 and 60. Thoracoscopic lobectomy was performed in 43 patients, wedge resection in 50, segmentectomy in 12 and mediastinal or pleural tumour excision in 4. Three patients (2.8%) required conversion to intubated one-lung ventilation because of vigorous mediastinal movement and dense diaphragmatic adhesions. Anaesthetic induction and operation had a median duration of 10.0 and 127.0 min, respectively. Operative complications developed in 13 patients with air leaks for more than 3 days and 1 patient required transfusion of blood products. The median postoperative chest drainage and hospital stay were 2.0 and 4.0 days, respectively. Non-intubated thoracoscopic surgery using internal intercostal nerve block, vagal block and targeted sedation is technically feasible and safe in surgical treatment of lung, mediastinal and pleural tumours in selected patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  13. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1) assess the gastric effects of brain stem DA application, 2) identify the DA receptor subtype, and, 3) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility.NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  14. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Directory of Open Access Journals (Sweden)

    A. Medeiros

    2004-12-01

    Full Text Available The effect of swimming training (ST on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12 and trained (T, N = 12 male Wistar rats (200-220 g. ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm. RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm, since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13% and myocyte dimension (21% were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  15. Chronic intermittent hypoxia-hypercapnia blunts heart rate responses and alters neurotransmission to cardiac vagal neurons.

    Science.gov (United States)

    Dyavanapalli, Jhansi; Jameson, Heather; Dergacheva, Olga; Jain, Vivek; Alhusayyen, Mona; Mendelowitz, David

    2014-07-01

    Patients with obstructive sleep apnoea experience chronic intermittent hypoxia-hypercapnia (CIHH) during sleep that elicit sympathetic overactivity and diminished parasympathetic activity to the heart, leading to hypertension and depressed baroreflex sensitivity. The parasympathetic control of heart rate arises from pre-motor cardiac vagal neurons (CVNs) located in nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX). The mechanisms underlying diminished vagal control of heart rate were investigated by studying the changes in blood pressure, heart rate, and neurotransmission to CVNs evoked by acute hypoxia-hypercapnia (H-H) and CIHH. In vivo telemetry recordings of blood pressure and heart rate were obtained in adult rats during 4 weeks of CIHH exposure. Retrogradely labelled CVNs were identified in an in vitro brainstem slice preparation obtained from adult rats exposed either to air or CIHH for 4 weeks. Postsynaptic inhibitory or excitatory currents were recorded using whole cell voltage clamp techniques. Rats exposed to CIHH had increases in blood pressure, leading to hypertension, and blunted heart rate responses to acute H-H. CIHH induced an increase in GABAergic and glycinergic neurotransmission to CVNs in NA and DMNX, respectively; and a reduction in glutamatergic neurotransmission to CVNs in both nuclei. CIHH blunted the bradycardia evoked by acute H-H and abolished the acute H-H evoked inhibition of GABAergic transmission while enhancing glycinergic neurotransmission to CVNs in NA. These changes with CIHH inhibit CVNs and vagal outflow to the heart, both in acute and chronic exposures to H-H, resulting in diminished levels of cardioprotective parasympathetic activity to the heart as seen in OSA patients. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  16. [Protection and functional repair of vagus nerve during the operation of cervical vagal paraganglioma].

    Science.gov (United States)

    Li, Wen; Chen, Zhe; Wu, Ruiqing; Zhang, Wenyan; Lu, Changli

    2012-08-01

    To explore the clinical anatomy and the methods to protect or reconstruct the continuity and function of vagus nerve during the operation of cervical vagal paraganglioma. Six cases of vagal paraganglioma were reviewed. All tumors were identified to wrap the cervical vagus nerve stem and excised during surgery. The operative modality was to trace the vagus nerve stem inside the tumor as far as possible, to reconstruct the continuity by way of vagus nerve anastomosis (3/6) or alternatively, other motor nerve transplantation (3/6). Postoperative treatment included steroid, neurotrophic medication and voice and swallowing rehabilitation. Two cases of the recurrent paraganglioma experienced aspiration during swallowing preoperatively and no aspiration after surgery. Choking was gradually reduced in four recurrent cases half to one year postoperatively. Hoarseness was improved in five cases (5/6) half to one year postoperatively, while one case remained prolonged obvious hoarseness. Three months postoperatively, the vocal cord fibrillation at the tumor-related side was observed during pronunciation in the end-to-end anastomosis cases (3/6), sublingual nerve-transplanted case (1/6) and deep cervical nerve-transplanted cases (1/6) under fiberoptic laryngoscope, and the mobility was even more obvious at the time of half an year postoperatively. While in another deep cervical nerve-transplanted case (1/6), the vocal cord demonstrated no obvious fibrillation. To carefully identify and preserve the vagus nerve fibers as much as possible during the operation of cervical vagal paraganglioma could significantly eliminate postoperative hoarseness and aspiration. End-to-end anastomosis, deep cervical nerve or sublingual nerve transplantation to resume the continuity of vagus nerve may improve the mobility of vocal cord thus the quality of voice and swallowing.

  17. Vagal reactivation after exercise and cardiac autonomic nervous activity in adult Fontan patients without pacemakers.

    Science.gov (United States)

    Eser, Prisca; Herzig, David; Vogt, Marcel; Stämpfli, Roger; Trovato, Moreno; Olstad, Daniela Schäfer; Trachsel, Lukas; Deluigi, Christina; Wustmann, Kerstin; Greutmann, Matthias; Tobler, Daniel; Stambach, Dominik; Schmid, Jean-Paul; Schwerzmann, Markus; Wilhelm, Matthias

    2016-10-01

    Patients with Fontan circulation have reduced heart rate variability (HRV) in supine position. However, neither cardiac autonomic nervous activity (CANA) in response to orthostatic challenge nor vagal reactivation by means of heart rate (HR) recovery after cessation of exercise have previously been investigated in Fontan patients. The aim of this study was to compare HRV in supine and standing position, as well as HR recovery between Fontan patients and healthy controls. Eight Fontan patients (4 male/4 female) without pacemakers and 12 healthy volunteers (5m/7f) with minimum age of 18years were recruited. HR was measured by Holter-electrocardiogram. HRV was measured in supine position and after orthostatic challenge. The power of the high frequency (HF: 0.15Hz-0.4Hz) and low frequency (LF: 0.04Hz-0.15Hz) bands was analysed by fast-Fourier transformation. HR recovery was determined at 30s and 60s after termination of a maximal exercise test. In both supine and standing position, total power, HF and LF power were reduced in Fontan patients compared to controls (by approximately a factor of 10) while there was no differences in LF/HF power ratio. Response to orthostatic challenge was blunted in absolute power but normal in relative power. HR recovery was not different between groups. Fontan patients have greatly reduced HRV, a blood-pressure dependent marker of CANA, but normal HR recovery, a blood pressure independent marker of vagal reactivation, suggesting that vagal activity may be normal, and only vascular capacitance reduced. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Vagal enhancement linking abnormal blood pressure response and subendocardial ischemia in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-01-01

    An abnormal blood pressure response to exercise has been reported to be associated with left ventricular subendocardial ischemia in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism remains unclear. We report a case of HCM with an abnormal blood pressure response and subendocardial ischemia, in which the analysis of heart rate variability revealed exercise-induced vagal enhancement. The present case highlights the possible mechanism linking abnormal blood pressure response and left ventricular subendocardial ischemia in patients with HCM. ©2013 Wiley Periodicals, Inc.

  19. Sudden Infant Death Syndrome, Infection, Prone Sleep Position, and Vagal Neuroimmunology

    Directory of Open Access Journals (Sweden)

    Paul Nathan Goldwater

    2017-11-01

    Full Text Available Recent findings suggest that infection (and sepsis stand alone as the only plausible mechanism of causation of sudden infant death syndrome (SIDS and accordingly achieves congruence with all clinicopathological and epidemiological findings. This review examines the role of infection in the pathogenesis of SIDS in the context of the major risk factor of prone sleep position. The study explores how sleep position could interact with the immune system and inflammatory response via vagal neural connections, which could play key roles in gut and immune homeostasis. A plausible and congruent clinicopathological and epidemiological paradigm is suggested.

  20. Sudden Infant Death Syndrome, Infection, Prone Sleep Position, and Vagal Neuroimmunology.

    Science.gov (United States)

    Goldwater, Paul Nathan

    2017-01-01

    Recent findings suggest that infection (and sepsis) stand alone as the only plausible mechanism of causation of sudden infant death syndrome (SIDS) and accordingly achieves congruence with all clinicopathological and epidemiological findings. This review examines the role of infection in the pathogenesis of SIDS in the context of the major risk factor of prone sleep position. The study explores how sleep position could interact with the immune system and inflammatory response via vagal neural connections, which could play key roles in gut and immune homeostasis. A plausible and congruent clinicopathological and epidemiological paradigm is suggested.

  1. The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects

    Directory of Open Access Journals (Sweden)

    Sathananthan M

    2014-07-01

    Full Text Available Matheni Sathananthan,1 Sayeed Ikramuddin,2 James M Swain,3,6 Meera Shah,1 Francesca Piccinini,4 Chiara Dalla Man,4 Claudio Cobelli,4 Robert A Rizza,1 Michael Camilleri,5 Adrian Vella1 1Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA; 2Division of General Surgery, University of Minnesota, Minneapolis, MN, USA; 3Division of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA; 4Department of Information Engineering, University of Padua, Padua, Italy; 5Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA; 6Scottsdale Healthcare Bariatric Center, Scottsdale, AZ, USA Purpose: Vagal interruption causes weight loss in humans and decreases endogenous glucose production in animals. However, it is unknown if this is due to a direct effect on glucose metabolism. We sought to determine if vagal blockade using electrical impulses alters glucose metabolism in humans. Patients and methods: We utilized a randomized, cross-over study design where participants were studied after 2 weeks of activation or inactivation of vagal nerve blockade (VNB. Seven obese subjects with impaired fasting glucose previously enrolled in a long-term study to examine the effect of VNB on weight took part. We used a standardized triple-tracer mixed meal to enable measurement of the rate of meal appearance, endogenous glucose production, and glucose disappearance. The 550 kcal meal was also labeled with 111In-diethylene triamine pentaacetic acid (DTPA to measure gastrointestinal transit. Insulin action and ß-cell responsivity indices were estimated using the minimal model. Results: Integrated glucose, insulin, and glucagon concentrations did not differ between study days. This was also reflected in a lack of effect on β-cell responsivity and insulin action. Furthermore, fasting and postprandial endogenous glucose production, integrated meal appearance, and glucose

  2. Pancreaticojejuno-jejunostomy during reconstruction of the afferent loop in surgery of radiation-induced afferent loop obstruction following pancreaticoduodenectomy with Roux-en-Y reconstruction.

    Science.gov (United States)

    Blouhos, Konstantinos; Boulas, Konstantinos A; Tsiomita, Evridiki; Papageorgiou, Irene; Ioannidis, Konstantinos; Hatzigeorgiadis, Anestis

    2014-03-01

    Radiation-induced afferent loop obstruction is a rare complication following pancreaticoduodenectomy and adjuvant radiotherapy. As in the setting of Roux-en-Y reconstruction endoscopic approaches are limited, surgery of this complication becomes inevitable. This study provides a new classification/management system of the radiation-induced obstruction of the afferent loop based on the extent and location of radiation injury, and describes the Pancreaticojejuno-jejunostomy, a novel technique to avoid revision of the pancreatic anastomosis during reconstruction of the afferent loop. Data were analyzed from nine patients who developed radiation-induced afferent loop obstruction after pancreaticoduodenectomy with single Roux limb reconstruction. One patient had type I obstruction and treated with by-pass surgery, seven patients had type II obstruction and treated with reconstruction including revision of the hepaticojejunostomy and Pancreaticojejuno-jejunostomy, and one patient had type III obstruction and treated with reconstruction including revision of the hepaticojejunostomy and the pancreatic anastomosis. Reconstruction along with Pancreaticojejuno-jejunostomy performed in six patients with type II radiation-induced afferent loop obstruction; reconstruction was not feasible for one patient. The median operative time was 149 min. No intraoperative complication was observed. By performing Pancreaticojejuno-jejunostomy we managed efficiently to convert a pancreatic anastomosis to an enteric anastomosis as one case of Grade B pancreatic fistula and no case of Pancreaticojejuno-jejunostomy stricture were observed, regarding short- and long-term results, respectively. The above technique may have a useful application in the surgical management of the radiation-induced afferent loop obstruction when endoscopy fails and by-pass surgery is inappropriate.

  3. Afferent-mediated modulation of the soleus muscle activity during the stance phase of human walking

    DEFF Research Database (Denmark)

    Nazarena, Mazzaro; Grey, Michael James; do Nascimento, Omar Feix

    2006-01-01

    -mediated contribution from muscle group II afferents, cutaneous and proprioceptive afferents from the foot, and load-sensitive afferents to the soleus EMG. Slow-velocity, small-amplitude ankle trajectory modifications were combined with the pharmaceutical depression of group II polysynaptic pathways with tizanidine......The aim of this study was to investigate the contribution of proprioceptive feedback to the amplitude modulation of the soleus muscle activity during human walking. We have previously shown that slow-velocity, small-amplitude ankle dorsiflexion enhancements and reductions applied during the stance...... hydrochloride, anaesthetic blocking of sensory information from the foot with injections of lidocaine hydrochloride, and modulation of load feedback by increasing and decreasing the body load. The depression of the group II afferents significantly reduced the soleus response to the ankle trajectory...

  4. Influence of Connexin40 on the renal myogenic response in murine afferent arterioles

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Sørensen, Charlotte Mehlin

    2015-01-01

    Renal autoregulation consists of two main mechanisms; the myogenic response and the tubuloglomerular feedback mechanism (TGF). Increases in renal perfusion pressure activate both mechanisms causing a reduction in diameter of the afferent arteriole (AA) resulting in stabilization of the glomerular...

  5. Paraventricular nucleus is involved in the central pathway of cardiac sympathetic afferent reflex in rats

    National Research Council Canada - National Science Library

    Ming-Kui Zhong; Yang-Can Duan; Ai-Dong Chen; Bo Xu; Xing-Ya Gao; Wei De; Guo-Qing Zhu

    2008-01-01

    ...) modulate the cardiac sympathetic afferent reflex (CSAR). The present study was designed to demonstrate more conclusively that the PVN is an important component of the central neurocircuitry of the CSAR...

  6. Input–Output Functions of Vestibular Afferent Responses to Air-Conducted Clicks in Rats

    National Research Council Canada - National Science Library

    Zhu, Hong; Tang, Xuehui; Wei, Wei; Maklad, Adel; Mustain, William; Rabbitt, Richard; Highstein, Steve; Allison, Jerome; Zhou, Wu

    2014-01-01

    ...) have proven useful in clinical assessment of vestibular function. VEMPs are commonly interpreted as a test of saccular function, based on neurophysiological evidence showing activation of saccular afferents by intense acoustic click stimuli...

  7. Organization of diencephalic and brainstem afferent projections to the lateral septum in the rat

    NARCIS (Netherlands)

    Luiten, Paul G.M.; Kuipers, Folkert; Schuitmaker, Hans

    1982-01-01

    Ascending diencephalic and brainstem afferents to the lateral septal column were studied by retrograde transport of horseradish peroxidase following microiontophoretic injections in the various subdivisions of the lateral septal area. Predominantly ispilateral cells, of which several coincide with

  8. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial

    NARCIS (Netherlands)

    May, M.; Gueler, F.; Barg-Hock, H.; Heiringhoff, K.H.; Engeli, S.; Heusser, K.; Diedrich, A.; Brandt, A.; Strassburg, C.P.; Tank, J.; Sweep, F.C.; Jordan, J.

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic

  9. Is the vagus nerve stimulation a way to decrease body weight in humans?

    Science.gov (United States)

    Bugajski, Andrzej; Gil, Krzysztof

    2012-01-01

    Obesity and its complications constitute an important health problem in growing number of people. Behavioral and pharmacological treatment is not much effective and surgical treatment carries too many threats. Promising method to be used is pharmacological or electric manipulation of vagus nerves. Regulation of food intake and energy utilization is a complex process regulated by centers in hypothalamus and brainstem which are receiving information from the peripheral via afferent neural pathways and sending peripherally adequate instructions by efferent neural pathways. In these signals conduction an important role plays vagus nerve. Additionally central nervous system stays under influence of endocrine, paracrine and neuroendocrine signals taking part in these regulations, functioning directly onto the centre or on the afferent neural endings. 80-90% fibers of vagus nerve are afferent fibers, so their action is mainly afferent, but possible contribution of the efferent fibers cannot be excluded. Efferent stimulation induces motility and secretion in the intestinal tract. Afferent unmyelinated C-type fibres of the vagus nerve are more sensitive and easily electrically stimulated. Information from vagus nerve is transmitted to nucleus tractus solitarius, which has projections to nucleus arcuate of the medio-basal hypothalamus, involved in the control of feeding behavior. It is suggested, that interaction onto the vagus nerve (stimulation or blocking) can be an alternative for other ways of obesity treatment. Through the manipulation of the vagus nerve activity the goal is achieved by influence on central nervous system regulating the energy homeostasis.

  10. Less Empathic and More Reactive: The Different Impact of Childhood Maltreatment on Facial Mimicry and Vagal Regulation.

    Directory of Open Access Journals (Sweden)

    Martina Ardizzi

    Full Text Available Facial mimicry and vagal regulation represent two crucial physiological responses to others' facial expressions of emotions. Facial mimicry, defined as the automatic, rapid and congruent electromyographic activation to others' facial expressions, is implicated in empathy, emotional reciprocity and emotions recognition. Vagal regulation, quantified by the computation of Respiratory Sinus Arrhythmia (RSA, exemplifies the autonomic adaptation to contingent social cues. Although it has been demonstrated that childhood maltreatment induces alterations in the processing of the facial expression of emotions, both at an explicit and implicit level, the effects of maltreatment on children's facial mimicry and vagal regulation in response to facial expressions of emotions remain unknown. The purpose of the present study was to fill this gap, involving 24 street-children (maltreated group and 20 age-matched controls (control group. We recorded their spontaneous facial electromyographic activations of corrugator and zygomaticus muscles and RSA responses during the visualization of the facial expressions of anger, fear, joy and sadness. Results demonstrated a different impact of childhood maltreatment on facial mimicry and vagal regulation. Maltreated children did not show the typical positive-negative modulation of corrugator mimicry. Furthermore, when only negative facial expressions were considered, maltreated children demonstrated lower corrugator mimicry than controls. With respect to vagal regulation, whereas maltreated children manifested the expected and functional inverse correlation between RSA value at rest and RSA response to angry facial expressions, controls did not. These results describe an early and divergent functional adaptation to hostile environment of the two investigated physiological mechanisms. On the one side, maltreatment leads to the suppression of the spontaneous facial mimicry normally concurring to empathic understanding of

  11. Computed tomographic features of afferent loop syndrome: pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Zissin, R. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Sapir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv (Israel); Hertz, M. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Paran, H. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Surgery ' A' , Sapir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv (Israel); Osadchy, A. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Sapir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv (Israel); Gayer, G. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Assaf Harofe Medical Center, Zrifin, Sackler Faculty of Medicine, Tel Aviv (Israel)

    2005-04-15

    This pictorial essay reviews the computed tomography (CT) findings of afferent loop syndrome (ALS) in various pathological conditions to demonstrate the contribution of a common imaging modality-that is, abdominal CT, used nowadays for various abdominal complaints-to the diagnosis of ALS. ALS is caused by obstruction of the duodenum and jejunum proximal to a gastrojejunostomy anastomosis. It is a rare complication after Billroth II subtotal gastrectomy and even more rare after total or subtotal gastrectomy with Roux-en-Y reconstruction. Although currently advanced medical treatment and endoscopic interventions have dramatically decreased the necessity of surgery for peptic ulcer disease, ALS may appear years after previously common operations. Alternatively, the use of surgical resection for early gastric cancer nowadays leads to an increasing rate of malignancy-related ALS. Clinically, ALS may be difficult to diagnose as its presentation may be vague and nonspecific, but it has a characteristic appearance on CT. Clinicians and radiologists should therefore be familiar with this rare complication. Prompt recognition and correct diagnosis of this syndrome and its probable etiology are important as a guide for treatment. This review illustrates the CT features of ALS in various conditions. (author)

  12. Afference copy as a quantitative neurophysiological model for consciousness.

    Science.gov (United States)

    Cornelis, Hugo; Coop, Allan D

    2014-06-01

    Consciousness is a topic of considerable human curiosity with a long history of philosophical analysis and debate. We consider there is nothing particularly complicated about consciousness when viewed as a necessary process of the vertebrate nervous system. Here, we propose a physiological "explanatory gap" is created during each present moment by the temporal requirements of neuronal activity. The gap extends from the time exteroceptive and proprioceptive stimuli activate the nervous system until they emerge into consciousness. During this "moment", it is impossible for an organism to have any conscious knowledge of the ongoing evolution of its environment. In our schematic model, a mechanism of "afference copy" is employed to bridge the explanatory gap with consciously experienced percepts. These percepts are fabricated from the conjunction of the cumulative memory of previous relevant experience and the given stimuli. They are structured to provide the best possible prediction of the expected content of subjective conscious experience likely to occur during the period of the gap. The model is based on the proposition that the neural circuitry necessary to support consciousness is a product of sub/preconscious reflexive learning and recall processes. Based on a review of various psychological and neurophysiological findings, we develop a framework which contextualizes the model and briefly discuss further implications.

  13. Dynamic GABAergic afferent modulation of AgRP neurons.

    Science.gov (United States)

    Garfield, Alastair S; Shah, Bhavik P; Burgess, Christian R; Li, Monica M; Li, Chia; Steger, Jennifer S; Madara, Joseph C; Campbell, John N; Kroeger, Daniel; Scammell, Thomas E; Tannous, Bakhos A; Myers, Martin G; Andermann, Mark L; Krashes, Michael J; Lowell, Bradford B

    2016-12-01

    Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues before ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the preconsummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor-expressing GABAergic vDMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, leptin receptor-expressing GABAergic vDMH neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior.

  14. Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

    OpenAIRE

    Feng, Bin; Brumovsky, Pablo R.; Gebhart, Gerald F.

    2010-01-01

    Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding charac...

  15. Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle afferent neurons

    OpenAIRE

    Ramachandra, Renuka; McGrew, Stephanie Y.; Baxter, James C.; Kiveric, Esad; Elmslie, Keith S.

    2012-01-01

    Muscle afferents are critical regulators of motor function (Group I and II) and cardiovascular responses to exercise (Group III and IV). However, little is known regarding the expressed voltage-dependent ion channels. We identified muscle afferent neurons in dorsal root ganglia (DRGs), using retrograde labeling to examine voltage-dependent sodium (NaV) channels. In patch-clamp recordings, we found that the dominant NaV current in the majority of identified neurons was insensitive to tetrodoto...

  16. Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle afferent DRG neurons

    OpenAIRE

    Lin, Yi-Wen; Chen, Chih-Cheng

    2015-01-01

    Muscle afferent neurons that express transient receptor potential vanilloid type I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle nociceptors plays an important role in the acid-induced hyperalgesic priming and the development of chronic hyperalgesia in a mouse model of fibromyalgia. To understand the electrophysiological properties of the TRPV1-expressing muscle afferent neurons, we used whole...

  17. The role of the renal afferent and efferent nerve fibers in heart failure

    Science.gov (United States)

    Booth, Lindsea C.; May, Clive N.; Yao, Song T.

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

  18. Synchronous malignant vagal paraganglioma with contralateral carotid body paraganglioma treated by radiation therapy

    Directory of Open Access Journals (Sweden)

    Devlina Chakarvarty

    2010-06-01

    Full Text Available Paragangliomas are rare tumors and very few cases of malignant vagal paraganglioma with synchronous carotid body paraganglioma have been reported. We report a case of a 20-year old male who presented with slow growing bilateral neck masses of eight years duration. He had symptoms of dysphagia to solids, occasional mouth breathing and hoarseness of voice. Fine needle aspiration cytology (FNAC performed where he lived showed a sinus histiocytosis and he was administered anti-tubercular treatment for six months without any improvement in his symptoms. His physical examination revealed pulsatile, soft to firm, non-tender swellings over the anterolateral neck confined to the upper-mid jugulo-diagastric region on both sides. Direct laryngoscopy examination revealed a bulge on the posterior pharyngeal wall and another over the right lateral pharyngeal wall. Magnetic resonance imaging (MRI, 99mTc-labeled octreotide scan and angiography diagnosed the swellings as carotid body paraganglioma, stage III on the right side with left-sided vagal malignant paraganglioma. Surgery was ruled out as a high morbidity with additional risk to life was expected due to the highly vascular nature of the tumor. The patient was treated with radiation therapy by image guided radiation to a dose of 5040cGy in 28 fractions. At a follow-up at 16 months, the tumors have regressed bilaterally and the patient can take solids with ease.

  19. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6

    Directory of Open Access Journals (Sweden)

    Yan Jin

    2012-01-01

    Full Text Available Abstract Background Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6 levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation. Results Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment. Conclusions Our results indicate that IL-6 enhances the excitability of dural afferents likely via ERK-mediated modulation of Nav1.7 and these responses

  20. Closing the loop of deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Romain eCARRON

    2013-12-01

    Full Text Available High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfils these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

  1. Spinal Fos labeling and penile erection elicited by stimulation of dorsal nerve of the rat penis.

    Science.gov (United States)

    Rampin, O; Gougis, S; Giuliano, F; Rousseau, J P

    1997-05-01

    Penile afferents present in the dorsal nerve of the penis (DNP) convey sensory information from the penis to the spinal cord and represent the afferent limb of reflexive erections. Immunocytochemical staining of Fos was used to identify spinal neurons that receive excitatory inputs from the DNP in anesthetized rats. Intracavernous pressure (ICP) was recorded as an index of erection. Dissection as well as stimulation of the DNP elicited a comparable increase in Fos staining. Labeling was present in the dorsal horn, the dorsal gray commissure, and the sacral parasympathetic nucleus, supporting the hypothesis of direct or indirect afferent projection from the penis and penile sheath in these areas. No change in ICP was observed in these rats. Stimulation of the DNP elicited both increased Fos labeling and ICP after spinalization, demonstrating the presence of a supraspinal inhibitory control exerted on the polysynaptic intraspinal circuitry responsible for reflexive penile erection.

  2. Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Salter Michael W

    2010-11-01

    Full Text Available Abstract Background The blood-brain barrier (BBB plays the crucial role of limiting exposure of the central nervous system (CNS to damaging molecules and cells. Dysfunction of the BBB is critical in a broad range of CNS disorders including neurodegeneration, inflammatory or traumatic injury to the CNS, and stroke. In peripheral tissues, the vascular-tissue permeability is normally greater than BBB permeability, but vascular leakage can be induced by efferent discharge activity in primary sensory neurons leading to plasma extravasation into the extravascular space. Whether discharge activity of sensory afferents entering the CNS may open the BBB or blood-spinal cord barrier (BSCB remains an open question. Results Here we show that peripheral nerve injury (PNI produced by either sciatic nerve constriction or transecting two of its main branches causes an increase in BSCB permeability, as assessed by using Evans Blue dye or horseradish peroxidase. The increase in BSCB permeability was not observed 6 hours after the PNI but was apparent 24 hours after the injury. The increase in BSCB permeability was transient, peaking about 24-48 hrs after PNI with BSCB integrity returning to normal levels by 7 days. The increase in BSCB permeability was prevented by administering the local anaesthetic lidocaine at the site of the nerve injury. BSCB permeability was also increased 24 hours after electrical stimulation of the sciatic nerve at intensity sufficient to activate C-fibers, but not when A-fibers only were activated. Likewise, BSCB permeability increased following application of capsaicin to the nerve. The increase in permeability caused by C-fiber stimulation or by PNI was not anatomically limited to the site of central termination of primary afferents from the sciatic nerve in the lumbar cord, but rather extended throughout the spinal cord and into the brain. Conclusions We have discovered that injury to a peripheral nerve and electrical stimulation of C

  3. Directional tuning of human forearm muscle afferents during voluntary wrist movements

    Science.gov (United States)

    Jones, Kelvin E; Wessberg, Johan; Vallbo, Åke B

    2001-01-01

    Single unit activity was recorded with the microneurography technique from sixteen spindle afferents and one Golgi tendon organ afferent originating from the forearm extensor muscles. Impulse rates were studied while subjects performed unobstructed aiming movements at the wrist in eight different directions 45 deg apart. In addition, similar imposed movements were performed while the subject was instructed to remain relaxed. Movement amplitudes were about 5 deg and the speed 10–30 deg s−1. Joint movements were translated to movements of a cursor on a monitor to provide visual feedback. Individual spindle afferents modulated their activity over a number of targets, i.e. were broadly tuned, during these aiming movements. The preferred direction for a spindle afferent was the same during both passive and active movements, indicating that the fusimotor effects associated with active contractions had little or no effect on the direction of tuning. The direction of tuning of individual spindle afferents could be predicted from the biomechanically inferred length changes of the parent muscle. Thus spindle afferents responded as stretch receptors, i.e. impulse rates increased with lengthening and decreased with shortening, in active as well as passive movements. Spindles from muscles, which continuously counteracted gravity exhibited a stretch response and directional tuning during the phase of movement alone whereas their position sensitivity was poor. In contrast, spindle afferents from the muscles that had no or minimal antigravity role were directionally tuned during both the dynamic and the static phase of the aiming task and their position sensitivity was substantially higher. In spite of the limited data base from three extensor muscles it could be demonstrated that wrist joint position was remarkably well encoded in the ensemble muscle spindle data. In some cases the ensemble muscle spindle data encoded the instantaneous trajectory of movement as well. PMID

  4. Central projections of the wing afferents in the hawkmoth, Agrius convolvuli.

    Science.gov (United States)

    Ando, Noriyasu; Wang, Hao; Shirai, Koji; Kiguchi, Kenji; Kanzaki, Ryohei

    2011-11-01

    Flight behaviors in various insect species are closely correlated with their mechanical and neuronal properties. Compared to locusts and flies which have been intensively studied, moths have "intermediate" properties in terms of the neurogenic muscle activations, power generation by indirect muscles, and two-winged-insect-like flapping behavior. Despite these unique characteristics, little is known about the neuronal mechanisms of flight control in moths. We investigated projections of the wing mechanosensory afferents in the central nervous system (CNS) of the hawkmoth, Agrius convolvuli, because the mechanosensory proprioceptive feedback has an essential role for flight control and would be presumably optimized for insect species. We conducted anterograde staining of nine afferent nerves from the fore- and hindwings. All of these afferents projected into the prothoracic, mesothoracic and metathoracic ganglia (TG1, 2 and 3) and had ascending fibers to the head ganglia. Prominent projection areas in the TG1-3 and suboesophageal ganglion (SOG) were common between the forewing, hindwing and contralateral forewing afferents, suggesting that information from different wings are converged at multiple levels presumably for coordinating wing flapping. On the other hand, differences of projections between the fore- and hindwing afferents were observed especially in projection areas of the tegulae in the TG1 and contralateral projections of the anterior forewing nerve in the TGs and SOG, which would reflect functional differences between corresponding mechanoreceptors on each wing. Afferents comprising groups of the campaniform sensilla at the wing bases had prominent ascending pathways to the SOG, resembling the head-neck motor system for gaze control in flies. Double staining of the wing afferents and flight or neck motoneurons also indicated potential connectivity between them. Our results suggest multiple roles of the wing proprioceptive feedback for flight and provide

  5. Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

    DEFF Research Database (Denmark)

    Damholt, M B; Arlien-Soeborg, P; Hilsted, L

    2006-01-01

    The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed...

  6. Dysfunctional muscarinic M(2) autoreceptors in vagally induced bronchoconstriction of conscious guinea pigs after the early allergic reaction

    NARCIS (Netherlands)

    TenBerge, REJ; Krikke, M; Teisman, ACH; Roffel, AF; Zaagsma, J

    1996-01-01

    We studied the function of autoinhibitory muscarinic M(2) receptors on vagal nerve endings in the airways of conscious, unrestrained, ovalbumin-sensitized guinea pigs after the early and late allergic reaction. For this purpose, the effects of the selective muscarinic M(2) receptor antagonist

  7. Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve.

    Science.gov (United States)

    Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Kamiya, Atsunori; Shishido, Toshiaki; Sugimachi, Masaru

    2017-11-08

    Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

  8. Effects of periodontal afferent inputs on corticomotor excitability in humans

    DEFF Research Database (Denmark)

    Zhang, Y; Boudreau, S; Wang, M

    2010-01-01

    The aim of the present study was to determine in humans whether local anaesthesia (LA) or nociceptive stimulation of the periodontal ligaments affects the excitability of the face primary motor cortex (MI) related to the tongue and jaw muscles, as measured by transcranial magnetic stimulation (TMS...... (MEP) stimulus-response curves and corticomotor maps were acquired for the tongue and masseter muscles before (baseline) and at 5, 30 and 60 min post-application of carbocain or capsaicin. Transcranial magnetic stimulation-MEP stimulus-response curves were also acquired at these time points...... for the first dorsal interosseous (FDI) as an internal control. Burning pain intensity and mechanical sensitivity ratings to a von Frey filament applied to the application site were recorded on an electronic visual analogue scale (VAS). All subjects reported a decreased mechanical sensitivity (anova: P = 0...

  9. Relative afferent pupillary defects in primary open-angle glaucoma--five years' experience.

    Science.gov (United States)

    Page, C J; Merritt, J C; Evans, B

    1985-12-01

    Afferent pupillary defects may accompany asymmetric primary open-angle glaucoma, though the exact incidence has not been reported. Charts were reviewed on 89 patients attending the Glaucoma/Uveitis Clinic at the North Carolina Memorial Hospital in Chapel Hill, North Carolina over a five-year period. All patients had primary open-angle glaucoma diagnosed by: (1) increased ocular tensions (22 mmHg) in the presence of open-anterior-chamber angles and (2) optic-nerve cupping and atrophy compatible with (3) pressure-dependent, visual-field loss. No subjects with secondary glaucomas, primary-angle-closure glaucoma, or ocular hypertension are included.The presence of the relative afferent pupillary defect was noted in 21 of 89 patients (23 percent). Sixteen of 70 black patients had relative afferent pupillary defect in the more severely affected eye, while five of 19 white patients demonstrated afferent pupils. Other demographic characteristics of this population are described. Two typical primary-open-angle glaucoma patients are discussed to demonstrate comparable changes within the optic nerves and Goldmann visual fields. The presence of the relative afferent pupillary defect best correlates with asymmetric, visual-field loss in the more severely affected eye.

  10. Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of Rats.

    Science.gov (United States)

    Kanda, Hirosato; Gu, Jianguo G

    2017-04-25

    Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/μm, and the tension was significantly decreased to ∼29 pN/μm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/μm by methyl-β-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. FUSIMOTOR EFFECTS OF MIDBRAIN STIMULATION ON JAW MUSCLE-SPINDLES OF THE ANESTHETIZED CAT

    NARCIS (Netherlands)

    TAYLOR, A; JUCH, PJW

    The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine

  12. Vagally-Mediated Heart Rate Variability and Indices of Wellbeing: Results of a Nationally Representative Study

    Science.gov (United States)

    Sloan, Richard P; Schwarz, Emilie; McKinley, Paula S; Weinstein, Maxine; Love, Gayle; Ryff, Carol; Mroczek, Daniel; Choo, Tse; Lee, Seonjoo; Seeman, Teresa

    2016-01-01

    Objective High frequency (HF) heart rate variability (HRV) has long been accepted as an index of cardiac vagal control. Recent studies report relationships between HF-HRV and indices of positive and negative affect, personality traits and wellbeing but these studies generally are based on small and selective samples. Method These relationships were examined using data from 967 participants in the second Midlife in the US (MIDUS II) study. Participants completed survey questionnaires on wellbeing and affect. HF-HRV was measured at rest. A hierarchical series of regression analyses examined relationships between these various indices and HF-HRV before and after adjustment for relevant demographic and biomedical factors. Results Significant inverse relationships were found only between indices of negative affect and HF-HRV. Relationships between indices of psychological and hedonic wellbeing and positive affect failed to reach significance. Conclusions These findings raise questions about relationships between cardiac parasympathetic modulation, emotion regulation, and indices of wellbeing. PMID:27570892

  13. Cardiac Vagal Control and Depressive Symptoms: The Moderating Role of Sleep Quality

    Science.gov (United States)

    Werner, Gabriela G.; Ford, Brett Q.; Mauss, Iris B.; Schabus, Manuel; Blechert, Jens; Wilhelm, Frank H.

    2017-01-01

    Lower cardiac vagal control (CVC) has been linked to greater depression. However, this link has not been consistently demonstrated, suggesting the presence of key moderators. Sleep plausibly is one such factor. Therefore, we investigated whether sleep quality moderates the link between CVC (quantified by high-frequency heart rate variability, HF-HRV) and depressive symptoms (assessed using established questionnaires) in 29 healthy women. Results revealed a significant interaction between HF-HRV and sleep quality in predicting depressive symptoms: participants with lower HF-HRV reported elevated depressive symptoms only when sleep quality was also low. In contrast, HF-HRV was not associated with depressive symptoms when sleep quality was high, suggesting a protective function of high sleep quality in the context of lower CVC. PMID:27149648

  14. Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans.

    NARCIS (Netherlands)

    Helmich, R.C.G.; Baumer, T.; Siebner, H.R.; Bloem, B.R.; Munchau, A.

    2005-01-01

    A conditioning electrical stimulus to a digital nerve can inhibit the motor-evoked potentials (MEPs) in adjacent hand muscles elicited by transcranial magnetic stimulation (TMS) to the contralateral primary motor cortex (M1) when given 25-50 ms before the TMS pulse. This is referred to as

  15. Cardiovascular autonomic effects of vagus nerve stimulation.

    Science.gov (United States)

    Garamendi-Ruiz, Iñigo; Gómez-Esteban, Juan Carlos

    2017-10-25

    The vagus nerve is responsible for the parasympathetic innervation of the major thoracic and abdominal organs. It also carries sensory afferent fibres from these viscera and reaches different brain structures. These connections have proven useful in the treatment of different diseases. Afferent stimulation of the left vagus nerve is used to treat epilepsy and major depression, and stimulation of the right vagus nerve is being tried for the treatment of heart failure. The device used for the therapy delivers intermittent stimuli. It is indicated worldwide for the treatment of drug-resistant epilepsy in patients who are not appropriate candidates for respective surgery. It has also received approval for the treatment of major depression, obesity and episodic cluster headache by the Food and Drug Administration. Randomised controlled trials and prospective studies have confirmed the efficacy and safety of this therapy in epilepsy. Nevertheless, sporadic cases of ventricular asystole have been reported. To evaluate the effect of vagus nerve stimulation therapy on the autonomic nervous system, different studies that assess heart function and blood pressure changes have been conducted, although the methods employed were not homogeneous. These studies have found subtle or no significant changes in heart rate variability and blood pressure in epileptic patients. Moreover, this therapy may reduce the risk of one of the most lethal conditions in epilepsy-sudden unexpected death.

  16. Light-Emitting Diode Phototherapy Reduces Nocifensive Behavior Induced by Thermal and Chemical Noxious Stimuli in Mice: Evidence for the Involvement of Capsaicin-Sensitive Central Afferent Fibers.

    Science.gov (United States)

    Pigatto, Glauce Regina; Coelho, Igor Santos; Aquino, Rosane Schenkel; Bauermann, Liliane Freitas; Santos, Adair Roberto Soares

    2017-07-01

    Low-intensity phototherapy using light fonts, like light-emitting diode (LED), in the red to infrared spectrum is a promising alternative for the treatment of pain. However, the underlying mechanisms by which LED phototherapy reduces acute pain are not yet well understood. This study investigated the analgesic effect of multisource LED phototherapy on the acute nocifensive behavior of mice induced by thermal and chemical noxious stimuli. The involvement of central afferent C fibers sensitive to capsaicin in this effect was also investigated. Mice exposed to multisource LED (output power 234, 390, or 780 mW and power density 10.4, 17.3, and 34.6 mW/cm2, respectively, from 10 to 30 min of stimulation with a wavelength of 890 nm) showed rapid and significant reductions in formalin- and acetic acid-induced nocifensive behavior. This effect gradually reduced but remained significant for up to 7 h after LED treatment in the last model used. Moreover, LED (390 mW, 17.3 mW/cm2/20 min) irradiation also reduced nocifensive behavior in mice due to chemical [endogenous (i.e., glutamate, prostaglandins, and bradykinin) or exogenous (i.e., formalin, acetic acid, TRPs and ASIC agonist, and protein kinase A and C activators)] and thermal (hot plate test) stimuli. Finally, ablating central afferent C fibers abolished LED analgesia. These experimental results indicate that LED phototherapy reduces the acute painful behavior of animals caused by chemical and thermal stimuli and that LED analgesia depends on the integrity of central afferent C fibers sensitive to capsaicin. These findings provide new information regarding the underlying mechanism by which LED phototherapy reduces acute pain. Thus, LED phototherapy may be an important tool for the management of acute pain.

  17. Intraurethral stimulation evokes bladder responses via 2 distinct reflex pathways.

    Science.gov (United States)

    Woock, John P; Yoo, Paul B; Grill, Warren M

    2009-07-01

    Recent animal studies have shown that selective activation of pudendal nerve branches can evoke bladder responses through 2 distinct reflex pathways. We examined intraurethral electrical stimulation as a minimally invasive means of selectively activating these pathways in the cat. Bladder responses evoked by intraurethral electrical stimulation were measured in alpha-chloralose anesthetized male cats at different stimulation frequencies, stimulation intensities and intraurethral locations. Intraurethral electrical stimulation evoked inhibitory and excitatory bladder reflexes depending on stimulation frequency and location. Stimulation in the penile urethra 0 to 3 cm from the urethral meatus at 33 Hz evoked bladder contraction and at 10 Hz it evoked bladder relaxation. These responses were abolished after bilateral transection of the dorsal penile nerves. Stimulation in the membranous urethra 5 to 7 cm from the urethral meatus at 2, 10 and 33 Hz evoked bladder contractions. These responses were abolished after bilateral transection of the cranial sensory nerves. Following acute spinal cord transection bladder contractions were still evoked by 33 Hz stimulation in the penile urethra but not by stimulation at any frequency in the membranous urethra. Intraurethral electrical stimulation selectively evoked bladder responses by activating 2 distinct pudendal afferent pathways. Responses depended on stimulation frequency and location. Intraurethral electrical stimulation is a valid means of determining the pathways involved in bladder responses evoked by pudendal nerve stimulation.

  18. Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye; Nielsen, Jens Bo

    2008-01-01

    Neural plasticity occurs throughout adult life in response to maturation, use and disuse. Recent studies have documented that H-reflex amplitudes increase following a period of immobilization. To elucidate the mechanisms contributing to the increase in H-reflex size following immobilization we...... inhibition of SOL Ia afferents and taken together suggest that GABAergic presynaptic inhibition of the SOL Ia afferents is decreased following 2 weeks of immobilization. The depression of the SOL H-reflex when evoked at intervals shorter than 10 s (homosynaptic post-activation depression) also decreased...... following immobilization, suggesting that the activity-dependent regulation of transmitter release from the afferents was also affected by immobilization. We observed no significant changes in disynaptic reciprocal Ia inhibition. Two weeks after cast removal measurements returned to pre immobilization...

  19. Structure of the afferent terminals in terminal ganglion of a cricket and persistent homology.

    Directory of Open Access Journals (Sweden)

    Jacob Brown

    Full Text Available We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets.

  20. Structure of the Afferent Terminals in Terminal Ganglion of a Cricket and Persistent Homology

    Science.gov (United States)

    Brown, Jacob; Gedeon, Tomáš

    2012-01-01

    We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals) into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets. PMID:22649516

  1. Contribution of afferent feedback to the soleus muscle activity during human locomotion

    DEFF Research Database (Denmark)

    Mazzaro, Nazarena; Grey, Michael James; Sinkjær, Thomas

    2005-01-01

    During the stance phase of the human step cycle, the ankle undergoes a natural dorsiflexion that stretches the soleus muscle. The afferent feedback resulting from this stretch enhances the locomotor drive. In this study a robotic actuator was used to slightly enhance or reduce the natural ankle...... enhancements was reduced when the group Ia afferents were blocked with peripheral ischemia at the thigh, and during high-frequency Achilles tendon vibration. However, neither ischemia nor tendon vibration affected the decrements in the SOL EMG during the dorsiflexion reductions. These findings give evidence...... of the contribution of afferent feedback to the SOL activity in an ongoing basis during the stance phase. The results suggest that mainly feedback from the group Ia pathways is responsible for the increments in the SOL EMG during the dorsiflexion enhancements. However, the decrements in the SOL activity might...

  2. Direct and indirect regulation of spinal cord Ia afferent terminal formation by the γ-Protocadherins

    Directory of Open Access Journals (Sweden)

    Tuhina ePrasad

    2011-12-01

    Full Text Available The Pcdh-γ gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons, do not undergo excessive apoptosis in Pcdh-γdel/del null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in Pcdh-γ mutants are expanded, clumped, and fill the space between individual motor neurons; quantitative analysis shows a ~2.5 fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons, many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-γ null mice by introduction of a Bax null allele. This indicates that loss of ventral interneurons, which act as intermediate Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-γ cluster using conditional mutants and multiple Cre transgenic lines (Wnt1-Cre for sensory neurons; Pax2-Cre for ventral interneurons; Hb9-Cre for motor neurons also revealed a direct requirement for the γ-Pcdhs in Ia neurons and ventral interneurons, but not in motor neurons themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of ventral interneurons that act as intermediate Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target ventral interneurons.

  3. Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle afferent neurons.

    Science.gov (United States)

    Ramachandra, Renuka; McGrew, Stephanie Y; Baxter, James C; Kiveric, Esad; Elmslie, Keith S

    2012-10-01

    Muscle afferents are critical regulators of motor function (Group I and II) and cardiovascular responses to exercise (Group III and IV). However, little is known regarding the expressed voltage-dependent ion channels. We identified muscle afferent neurons in dorsal root ganglia (DRGs), using retrograde labeling to examine voltage-dependent sodium (Na(V)) channels. In patch-clamp recordings, we found that the dominant Na(V) current in the majority of identified neurons was insensitive to tetrodotoxin (TTX-R), with Na(V) current in only a few (14%) neurons showing substantial (>50%) TTX sensitivity (TTX-S). The TTX-R current was sensitive to a Na(V)1.8 channel blocker, A803467. Immunocytochemistry demonstrated labeling of muscle afferent neurons by a Na(V)1.8 antibody, which further supported expression of these channels. A portion of the TTX-R Na(V) current appeared to be noninactivating during our 25-ms voltage steps, which suggested activity of Na(V)1.9 channels. The majority of the noninactivating current was insensitive to A803467 but sensitive to extracellular sodium. Immunocytochemistry showed labeling of muscle afferent neurons by a Na(V)1.9 channel antibody, which supports expression of these channels. Further examination of the muscle afferent neurons showed that functional TTX-S channels were expressed, but were largely inactivated at physiological membrane potentials. Immunocytochemistry showed expression of the TTX-S channels Na(V)1.6 and Na(V)1.7 but not Na(V)1.1. Na(V)1.8 and Na(V)1.9 appear to be the dominant functional sodium channels in small- to medium-diameter muscle afferent neurons. The expression of these channels is consistent with the identification of these neurons as Group III and IV, which mediate the exercise pressor reflex.

  4. Information analysis of posterior canal afferents in the turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Rowe, Michael H; Neiman, Alexander B

    2012-01-24

    We have used sinusoidal and band-limited Gaussian noise stimuli along with information measures to characterize the linear and non-linear responses of morpho-physiologically identified posterior canal (PC) afferents and to examine the relationship between mutual information rate and other physiological parameters. Our major findings are: 1) spike generation in most PC afferents is effectively a stochastic renewal process, and spontaneous discharges are fully characterized by their first order statistics; 2) a regular discharge, as measured by normalized coefficient of variation (cv*), reduces intrinsic noise in afferent discharges at frequencies below the mean firing rate; 3) coherence and mutual information rates, calculated from responses to band-limited Gaussian noise, are jointly determined by gain and intrinsic noise (discharge regularity), the two major determinants of signal to noise ratio in the afferent response; 4) measures of optimal non-linear encoding were only moderately greater than optimal linear encoding, indicating that linear stimulus encoding is limited primarily by internal noise rather than by non-linearities; and 5) a leaky integrate and fire model reproduces these results and supports the suggestion that the combination of high discharge regularity and high discharge rates serves to extend the linear encoding range of afferents to higher frequencies. These results provide a framework for future assessments of afferent encoding of signals generated during natural head movements and for comparison with coding strategies used by other sensory systems. This article is part of a Special Issue entitled: Neural Coding. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Systemic administration of monosodium glutamate elevates intramuscular glutamate levels and sensitizes rat masseter muscle afferent fibers.

    Science.gov (United States)

    Cairns, Brian E; Dong, Xudong; Mann, Mandeep K; Svensson, Peter; Sessle, Barry J; Arendt-Nielsen, Lars; McErlane, Keith M

    2007-11-01

    There is evidence that elevated tissue concentrations of glutamate may contribute to pain and sensitivity in certain musculoskeletal pain conditions. In the present study, the food additive monosodium glutamate (MSG) was injected intravenously into rats to determine whether it could significantly elevate interstitial concentrations of glutamate in the masseter muscle and whether MSG administration could excite and/or sensitize slowly conducting masseter afferent fibers through N-methyl-D-aspartate (NMDA) receptor activation. The interstitial concentration of glutamate after systemic injection of isotonic phosphate-buffered saline (control) or MSG (10 and 50mg/kg) was measured with a glutamate-selective biosensor. The pre-injection baseline interstitial concentration of glutamate in the rat masseter muscle was 24+/-11 microM. Peak interstitial concentration after injection of 50mg/kg MSG was 63+/-18 microM and remained elevated above baseline for approximately 18 min. In vivo single unit recording experiments were undertaken to assess the effect of MSG (50mg/kg) on masseter afferent fibers. Injection of MSG evoked a brief discharge in one afferent fiber, and significantly decreased ( approximately 25%) the average afferent mechanical threshold (n=10) during the first 5 min after injection of MSG. Intravenous injection of ketamine (1mg/kg), 5 min prior to MSG, prevented the MSG-induced decreases in the mechanical threshold of masseter afferent fibers. The present results indicate that a 2- to 3-fold elevation in interstitial glutamate levels in the masseter muscle is sufficient to excite and induce afferent mechanical sensitization through NMDA receptor activation. These findings suggest that modest elevations of interstitial glutamate concentration could alter musculoskeletal pain sensitivity in humans.

  6. Peptide and lipid modulation of glutamatergic afferent synaptic transmission in the solitary tract nucleus

    Directory of Open Access Journals (Sweden)

    Michael C. Andresen

    2013-01-01

    Full Text Available The brainstem nucleus of the solitary tract (NTS holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current (EPSC often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g. hypothalamus neuron sources. Presynaptic receptors for angiotensin (AT1, vasopressin (V1a, oxytocin (OT, opioid (MOR, ghrelin (GHSR1 and cholecystokinin (CCK differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 (TRPV1 and the cannabinoid receptor (CB1 that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

  7. Modeling the Afferent Dynamics of the Baroreflex Control System

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.; Mahdi, Adam; Sturdy, Jacob

    2013-01-01

    In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation...... strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate......-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we...

  8. After-effects of peripheral neurostimulation on brain plasticity and ankle function in chronic stroke: The role of afferents recruited.

    Science.gov (United States)

    Beaulieu, Louis-David; Massé-Alarie, Hugo; Camiré-Bernier, Samuel; Ribot-Ciscar, Édith; Schneider, Cyril

    2017-09-01

    This study tested the after-effects of neuromuscular electrical stimulation (NMES), repetitive peripheral magnetic stimulation (rPMS) and muscle tendon vibration (VIB) on brain plasticity and sensorimotor impairments in chronic stroke to investigate whether different results could depend on the nature of afferents recruited by each technique. Fifteen people with chronic stroke participated in five sessions (one per week). Baseline measures were collected in session one, then, each participant received 4 randomly ordered interventions (NMES, rPMS, VIB and a 'control' intervention of exercises). Interventions were applied to the paretic ankle muscles and parameters of application were matched as closely as possible. Standardized clinical measures of the ankle function on the paretic side and transcranial magnetic stimulation (TMS) outcomes of both primary motor cortices (M1) were collected at pre- and post-application of each intervention. The ankle muscle strength was significantly improved by rPMS and VIB (P≤0.02). rPMS influenced M1 excitability (increase in the contralesional hemisphere, P=0.03) and inhibition (decrease in both hemispheres, P≤0.04). The group mean of a few clinical outcomes improved across sessions, i.e. independently of the order of interventions. Some TMS outcomes at baseline could predict the responsiveness to rPMS and VIB. This original study suggests that rPMS and VIB were efficient to drive M1 plasticity and sensorimotor improvements, likely via massive inflows of 'pure' proprioceptive information generated. Usefulness of some TMS outcomes to predict which intervention a patient could be more responsive to should be further tested in future studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Impaired heart rate variability in patients with non-diabetic chronic kidney disease — Prominent disruption of vagal control and daily fluctuation

    Directory of Open Access Journals (Sweden)

    Hisaki Makimoto

    2015-12-01

    Conclusion: The circadian autonomic, particularly vagal, fluctuations were impaired in non-diabetic CKD patients independently from aging and comorbidities. Further research is required to assess the association between this impairment and prognosis of CKD patients.

  10. Cardiac vagal control and theoretical models of co-occurring depression and anxiety: a cross-sectional psychophysiological study of community elderly

    National Research Council Canada - National Science Library

    Chen, Hsi-Chung; Yang, Cheryl C H; Kuo, Terry B J; Su, Tung-Ping; Chou, Pesus

    2012-01-01

    In order to elucidate the complex relationship between co-occurring depression and anxiety with cardiac autonomic function in the elderly, this study examined the correlation between cardiac vagal control (CVC...

  11. Development of an ex Vivo Method for Multi-unit Recording of Microbiota-Colonic-Neural Signaling in Real Time

    Directory of Open Access Journals (Sweden)

    Maria M. Buckley

    2018-02-01

    Full Text Available Background and Objectives: Bidirectional signaling between the gastrointestinal tract and the brain is vital for maintaining whole-body homeostasis. Moreover, emerging evidence implicates vagal afferent signaling in the modulation of host physiology by microbes, which are most abundant in the colon. This study aims to optimize and advance dissection and recording techniques to facilitate real-time recordings of afferent neural signals originating in the distal colon.New Protocol: This paper describes a dissection technique, which facilitates extracellular electrophysiological recordings from visceral pelvic, spinal and vagal afferent neurons in response to stimulation of the distal colon.Examples of Application: Focal application of 75 mM KCl to a section of distal colon with exposed submucosal or myenteric nerve cell bodies and sensory nerve endings evoked activity in the superior mesenteric plexus and the vagal nerve. Noradrenaline stimulated nerve activity in the superior mesenteric plexus, whereas application of carbachol stimulated vagal nerve activity. Exposure of an ex vivo section of distal colon with an intact colonic mucosa to peptidoglycan, but not lipopolysaccharide, evoked vagal nerve firing.Discussion: Previous studies have recorded vagal signaling evoked by bacteria in the small intestine. The technical advances of this dissection and recording technique facilitates recording of afferent nerve signals evoked in extrinsic sensory pathways by neuromodulatory reagents applied to the distal colon. Moreover, we have demonstrated vagal afferent activation evoked by bacterial products applied to the distal colonic mucosa. This protocol may contribute to our understanding of functional bowel disorders where gut-brain communication is dysfunctional, and facilitate real-time interrogation of microbiota-gut-brain signaling.

  12. Cold-Sensitive Corneal Afferents Respond to a Variety of Ocular Stimuli Central to Tear Production: Implications for Dry Eye Disease

    OpenAIRE

    Hirata, Harumitsu; Meng, Ian D.

    2010-01-01

    Innocuous “cold” cornea afferents were excited by the ocular stimuli (drying, cooling, evaporation, and hyperosmolar stress of the cornea) that normally produce tears. Dysfunction of these corneal afferents may be responsible for some forms of dry eye.

  13. Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor

    Directory of Open Access Journals (Sweden)

    Hulse Richard P

    2012-06-01

    Full Text Available Abstract Background Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. Results Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT mice. 7-days after

  14. Morphological and electrophysiological features of motor neurons and putative interneurons in the dorsal vagal complex of rats and mice

    Science.gov (United States)

    Gao, Hong; Glatzer, Nicholas R.; Williams, Kevin W.; Derbenev, Andrei V.; Liu, Dan; Smith, Bret N.

    2009-01-01

    The dorsal motor nucleus of the vagus (DMV) contains preganglionic motor neurons that control viscera along the subdiaphragmatic digestive tract, but may also contain neurons that do not project to the viscera. Neurons that expressed EGFP 60-72 h subsequent to PRV-152 inoculation of vagal terminals in the stomach wall were targeted for whole-cell patch-clamp recording and biocytin filling in transverse brainstem slices from rats and their quantitative morphological and electrophysiological characteristics were compared with uninfected cells. Over 90% of PRV-152 labeled neurons were also labeled subsequent to intraperitoneal injection of FluoroGold, indicating most were preganglionic motor neurons. In reconstructed neurons with an identifiable axon trajectory, two cellular subtypes were distinguished. The axon projected ventrolaterally from the DMV in 44 of 49 cells and these were likely to be vagal motor neurons. Axons of other neurons ramified within the nucleus tractus solitarius (NTS) or DMV. These cells were smaller and otherwise morphologically distinct from putative motor neurons. Transgenic mice with GFP-expressing inhibitory neurons (i.e., GIN mice) were used to identify a GABAergic subset vagal neurons. These neurons had locally-ramifying axons and formed a morphologically distinct subset of DMV cells, which were similar in size and axon trajectory to GABAergic neurons in the NTS. Most neurons in the DMV therefore possess morphological features of motor neurons, but locally projecting cells and inhibitory neurons with distinct morphological features are also found within the DMV. These cells likely contribute to regulation of vagal function. PMID:19619517

  15. Na+-independent, nifedipine-resistant rat afferent arteriolar Ca2+ responses to noradrenaline

    DEFF Research Database (Denmark)

    Salomonsson, Max; Braunstein, Thomas Hartig; von Holstein-Rathlou, Niels-Henrik

    2010-01-01

    Abstract Aim: In rat afferent arterioles we investigated the role of Na(+) entry in noradrenaline (NA)-induced depolarization and voltage-dependent Ca(2+) entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non-voltage-dependent Ca(2+) entry. Methods...

  16. AFFERENT RESPONSE OF A HEAD CANAL NEUROMAST OF THE RUFF (ACERINA-CERNUA) LATERAL LINE

    NARCIS (Netherlands)

    WUBBELS, RJ

    1. The fourth neuromast of the supra-orbital canal of the ruff lateral line is innervated by 300-400 fibres. 2. Afferent activity of 46 fibres was investigated as a function of stimulus amplitude and of stimulus frequency. 3. The dynamic range of the fibres exceeded 30 dB. 4. The gain with respect

  17. Mutant α-Synuclein Overexpression Induces Stressless Pacemaking in Vagal Motoneurons at Risk in Parkinson's Disease.

    Science.gov (United States)

    Lasser-Katz, Efrat; Simchovitz, Alon; Chiu, Wei-Hua; Oertel, Wolfgang H; Sharon, Ronit; Soreq, Hermona; Roeper, Jochen; Goldberg, Joshua A

    2017-01-04

    -synuclein pathology (e.g., Lewy bodies) is not directly related to the degree of neurodegeneration across various vulnerable neuronal populations. Here, we show that, in contrast to dopamine neurons in the substantia nigra, vagal motoneurons do not enhance their excitability and oxidative load in response to chronic mutant α-synuclein overexpression. Rather, by downregulating their voltage-activated calcium channels, vagal motoneurons acquire a stressless form of pacemaking that diminishes mitochondrial and cytosolic oxidative stress. Emulating this endogenous adaptive response to α-synuclein overexpression could lead to novel strategies to protect dopamine neurons and perhaps delay the onset of Parkinson's disease. Copyright © 2017 the authors 0270-6474/17/370048-11$15.00/0.

  18. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I.

    Science.gov (United States)

    Yuan, Hsiangkuo; Silberstein, Stephen D

    2016-01-01

    The vagus nerve (VN), the "great wondering protector" of the body, comprises an intricate neuro-endocrine-immune network that maintains homeostasis. With reciprocal neural connections to multiple brain regions, the VN serves as a control center that integrates interoceptive information and responds with appropriate adaptive modulatory feedbacks. While most VN fibers are unmyelinated C-fibers from the visceral organs, myelinated A- and B-fiber play an important role in somatic sensory, motor, and parasympathetic innervation. VN fibers are primarily cholinergic but other noncholinergic nonadrenergic neurotransmitters are also involved. VN has four vagal nuclei that provide critical controls to the cardiovascular, respiratory, and alimentary systems. Latest studies revealed that VN is also involved in inflammation, mood, and pain regulation, all of which can be potentially modulated by vagus nerve stimulation (VNS). With a broad vagal neural network, VNS may exert a neuromodulatory effect to activate certain innate "protective" pathways for restoring health. © 2015 American Headache Society.

  19. Nitric oxide in the afferent synaptic transmission of the axolotl vestibular system.

    Science.gov (United States)

    Flores, A; Soto, E; Vega, R

    2001-01-01

    This study was performed using intracellular and multiunit extracellular recording techniques in order to characterize the role of nitric oxide in the afferent synaptic transmission of the vestibular system of the axolotl (Ambystoma tigrinum). Bath application of nitric oxide synthase inhibitors N(G)-nitro-L-arginine (0.01microM to 10microM) and N-nitro-L-arginine methyl ester hydrochloride (0.1microM to 1000microM) elicited a dose-dependent decrease in the basal discharge of the semicircular canal afferent fibers. N(G)-Nitro-L-arginine also diminished the response to mechanical stimuli. Moreover, N(G)-nitro-L-arginine (1microM) produced a hyperpolarization associated with a decrease in the spike discharge and diminished the frequency of the excitatory postsynaptic potentials on afferent fibers recorded intracellularly. Nitric oxide donors were also tested: (i) S-nitroso-N-acetyl-DL-penicillamine (0.1microM to 100microM) increased the basal discharge and the response to mechanical stimuli. At the maximum effective concentration (100microM) this drug affected neither the amplitude nor the frequency of the excitatory postsynaptic potentials. However, it slightly depolarized the afferent neurons and decreased their input resistance. (ii) 3-Morpholino-sydnonimine hydrochloride did not significantly affect the basal discharge or the mechanically evoked peak response of afferent neurons at any of the concentrations used (1microM to 1000microM). However, after 10min of perfusion in the bath, 1microM and 10microM 3-morpholino-sydnonimine hydrochloride significantly modified the baseline of the mechanically evoked response, producing an increase in the mean spike discharge of the afferent fibers. These results indicate that nitric oxide may have a facilitatory role on the basal discharge and on the response to mechanical stimuli of the vestibular afferent fibers. Thus, nitric oxide probably participates in the sensory coding and adaptative changes of vestibular input in

  20. Detection of weak synaptic interactions between single Ia afferent and motor-unit spike trains in the decerebrate cat.

    Science.gov (United States)

    Conway, B A; Halliday, D M; Rosenberg, J R

    1993-11-01

    1. Spike trains from identified single Ia afferents from soleus and lateral gastrocnemius muscles were recorded (while 'in continuity' with the spinal cord) simultaneously with single-motor-unit EMG spike trains from the same muscles in decerebrate cats. 2. A total of 143 Ia afferent-motor-unit pairs were examined for the presence of correlated activity between the Ia afferent and motor-unit and between the motor-unit and Ia afferent. Four types of correlation were identified on the basis of the cross-intensity function estimated for individual Ia afferent-motor-unit pairs. These correlations were attributed to the absence or presence of a central Ia afferent-motoneurone interaction or a peripheral motor-unit-muscle spindle interaction. 3. In addition to the cross-correlation-based second-order cross-intensity function, third-order cumulants were defined and used further to investigate Ia afferent-motor-unit interactions. A third-order cumulant density-based approach to signal processing offers improved signal-to-noise ratios, compared with the traditional product density approach, for parameters characterizing certain kinds of linear processes as well as a description of non-linear interactions. Two classes of third-order relations were described. One class was associated with a strong central connection and the other with a weak central connection. 4. Third-order cumulants estimated for Ia afferent-motor-unit pairs with significant second-order central correlations were able to detect a period of decreased motoneuronal excitability. In addition, temporal summation prior to spike initiation could be identified in cases where the afferent discharge was suitably high. 5. Third-order cumulants estimated for Ia afferent-motor-unit pairs in which no significant second-order central correlation existed identified the presence of weak synaptic interactions. It is argued that these interactions result from the summation from the recorded Ia afferent discharge and other

  1. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    Science.gov (United States)

    Groth, Michael; Helbig, Tanja; Grau, Veronika; Kummer, Wolfgang; Haberberger, Rainer V

    2006-01-01

    Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative) were significantly more frequent among pleural (35%) than pulmonary afferents (20%). TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung) and 48% (pleura) of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive). Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli. PMID:16813657

  2. Runx1-deficient afferents impair visceral nociception, exacerbating dextran sodium sulfate-induced colitis.

    Science.gov (United States)

    Hung, Shih-Ping; Sheu, Ming-Jen; Ma, Ming Chieh; Hu, Jui-Ting; Sun, Ya-Yun; Lee, Chin-Cheng; Chung, Yuan-Chiang; Tsai, Yi-Ju; Wang, Jing-Yuan; Chen, Chih-Li

    2014-01-01

    Colitis is a group of inflammatory and auto-immune disorders that affect the tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced animal models of colitis have indicated that nociceptive afferents or neuropeptides have differing effects on GI inflammation. However, the molecular mechanisms involved in visceral pain and the role of visceral sensory afferents involved in the modulation of colitis remains unclear. A previous study demonstrated that Runx1, a Runt domain transcription factor, is restricted to nociceptors. In these neurons, Runx1 regulates the expression of numerous ion channels and receptors, controlling the lamina-specific innervation patterns of nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit specific defects in thermal and neuropathic pain. To examine the function of Runx1 in visceral nociception, we employed double-transgenic mice (WntCre: Runx1(F/F)), in which the expression of Runx1 was specifically disrupted in the sensory neurons. To determine the role of Runx1 in visceral pain sensation, the WntCre: Runx1(F/F) mice and their control littermates (Runx1(F/F)) were treated using dextran sodium sulfate (DSS) to induce colitis. The results indicated that disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the phenotypes in murine DSS-induced colitis; (3) a differential effect on the production of pro- and anti-inflammatory cytokines in the colon tissues isolated from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and (4) alteration of the distribution of lymphocytes and mast cells in mucosa. These results show that the function of Runx1 in sensory afferents is vital for modulating visceral pain and the neuro-immune axis. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Comparação entre métodos de avaliação da modulação vagal cardíaca Comparison of assessment methods of cardiac vagal modulation

    Directory of Open Access Journals (Sweden)

    Vagner Clayton de Paiva

    2011-12-01

    Full Text Available FUNDAMENTO: Diversos métodos têm sido utilizados para avaliar a modulação vagal cardíaca; entretanto, há lacunas quanto a associação e acurácia desses métodos. OBJETIVO: Investigar a associação entre três métodos válidos, reprodutíveis e comumente utilizados para avaliação da modulação vagal cardíaca, e comparar as suas acurácias. MÉTODOS: Trinta homens saudáveis (23 ± 4 anos e 15 homens com coronariopatia (61 ± 10 anos foram avaliados em ordem contrabalanceada pela Variabilidade da Frequência Cardíaca (VFC; variáveis: domínio do tempo = pNN50, DPNN e RMSSD, domínio da frequência = AF ms² e AF u.n., Arritmia Sinusal Respiratória (ASR e Teste de Exercício de 4 segundos (T4s. RESULTADOS: Indivíduos saudáveis apresentaram maior modulação vagal nos três métodos (p BACKGROUND: Several methods have been used to assess cardiac vagal modulation, but there are gaps regarding the association and accuracy of these methods. OBJECTIVE: To investigate the association between three valid, reproducible and commonly methods used to assess cardiac vagal modulation and compare their accuracies. METHODS: Thirty healthy men (23 ± 4 years and 15 men with coronary artery disease (61 ± 10 years were evaluated in counterbalanced design by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u., Respiratory Sinus Arrhythmia (RSA and 4-second Exercise Test (T4s. Thirty healthy men (23 ± 4 years and 15 men with coronary artery disease (61 ± 10 years were evaluated in counterbalanced order by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u., Respiratory Sinus Arrhythmia (RSA and 4-second Exercise Test (T4s. RESULTS: Healthy subjects had higher vagal modulation by the three methods (p <0.05. There was a correlation in the healthy group (p <0.05 between the results of HRV (SDNN and pNN50 and

  4. Postural stability is altered by the stimulation of pain but not warm receptors in humans

    Directory of Open Access Journals (Sweden)

    Corbeil Philippe

    2003-10-01

    Full Text Available Abstract Background It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Methods Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively. For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. Results The stimulation of the warm receptors (40 degrees C did not induce any postural deterioration. With pain (45 degrees C, subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure. Conclusions A non

  5. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans.

    Science.gov (United States)

    Frangos, Eleni; Ellrich, Jens; Komisaruk, Barry R

    2015-01-01

    Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as to whether or not the ABVN projects to the NTS in humans. To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the "classical" central vagal projections in humans. Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the central vagal projections (corrected; brainstem P < 0.01, forebrain P < 0.05), followed by a whole-brain analysis (corrected, P < 0.05). Cymba conchae stimulation, compared to earlobe (control) stimulation, produced significant activation of the "classical" central vagal projections, e.g., widespread activity in the ipsilateral NTS, bilateral spinal trigeminal nucleus, dorsal raphe, locus coeruleus, and contralateral parabrachial area, amygdala, and nucleus accumbens. Bilateral activation of the paracentral lobule was also observed. Deactivations were observed bilaterally in the hippocampus and hypothalamus. These findings provide evidence in humans that the central projections of the ABVN are consistent with the "classical" central vagal projections and can be accessed non-invasively via the external ear. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats.

    Science.gov (United States)

    Xiao, Bo; Zanoun, Rami R; Carvell, George E; Simons, Daniel J; Washington, Kia M

    2016-03-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures-notably evoked firing rates-closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury. Copyright © 2016 the American Physiological Society.

  7. BET 2: Ice water immersion, other vagal manoeuvres or adenosine for SVT in children.

    Science.gov (United States)

    Campbell, Marion; Buitrago, Silvia Ruiz

    2017-01-01

    A short cut review was carried out to establish whether a vagal manoeuvre was better than or as good as adenosine at safely terminating supraventricular tachycardia in children. Forty unique papers were found in Medline and Embase using the reported searches, of which five were relevant. A hand search of the forty unique citations identified a further nine relevant papers. Thus, 14 papers presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence on the management of SVT in children is made up of poor-quality retrospective cohort studies or case series. This best evidence shows that ice water to the face appears to be a safe, quick, effective and non-invasive treatment for paediatric SVT. Adenosine also appears safe and effective, but is more invasive. Valsalva and carotid sinus massage are less effective. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Early determinants of vagal activity at preschool age - With potential dependence on sex.

    Science.gov (United States)

    Kühne, Britta; Genser, Bernd; De Bock, Freia

    2016-12-01

    In children, autonomic nervous function is related to various highly prevalent health problems and might therefore represent an early indicator of ill health. We aimed to investigate the role of early-life exposures and physical activity (PA) as potential determinants of autonomic function at preschool age. We used an existing longitudinal data set of repeated vagal tone measurements (assessed via heart rate recovery (HRR)) and retrospectively assessed early-life exposures in 1052 children (mean age: 59.4months, 47.5% girls) from 52 preschools in Germany recruited from 2008 to 2010. HRR 1min after submaximal exercise served as primary outcome. Through multilevel linear regression analysis adjusted for demographic and socioeconomic factors, we assessed the association between repeatedly measured HRR and pregnancy smoking status, breastfeeding and objectively measured PA. Besides significant regression coefficients for previously described correlates of HRR (sex, age), we could show positive associations of HRR with breastfeeding (six versus zero months: +4.2 beats per minute (BPM), p=0.004) and PA (+1.0BPM for 10min increase of moderate-to-vigorous PA/day, pearly pre- and postnatal exposures seem to have long-lasting effects on children's autonomic function, still recordable at preschool age. Our data suggest that these effects might be sex-dependent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection.

    Science.gov (United States)

    Villarreal-Calderon, Rafael; Torres-Jardón, Ricardo; Palacios-Moreno, Juan; Osnaya, Norma; Pérez-Guillé, Beatriz; Maronpot, Robert R; Reed, William; Zhu, Hongtu; Calderón-Garcidueñas, Lilian

    2010-12-01

    Mexico City (MC) residents exposed to fine particulate matter and endotoxin exhibit inflammation of the olfactory bulb, substantia nigra, and vagus nerve. The goal of this study was to model these endpoints in mice and examine the neuroprotective effects of chocolate. Mice exposed to MC air received no treatment or oral dark chocolate and were compared to clean-air mice either untreated or treated intraperitoneally with endotoxin. Cyclooxygenase-2 (COX-2), interleukin 1 beta (IL-1β), and CD14 messenger RNA (mRNA) were quantified after 4, 8, and 16 months of exposure in target brain regions. After 16 months of exposure, the dorsal vagal complex (DVC) exhibited significant inflammation in endotoxin-treated and MC mice (COX-2 and IL-1β PMexico City mice had olfactory bulb upregulation of CD14 (P=.002) and significant DVC imbalance in genes for antioxidant defenses, apoptosis, and neurodegeneration. These findings demonstrate sustained DVC inflammation in mice exposed to MC air, which is mitigated by chocolate administration. © The Author(s) 2010

  10. Mothers' Vagal Regulation During the Still-Face Paradigm: Normative Reactivity and Impact of Depression Symptoms

    Science.gov (United States)

    Oppenheimer, Julia E.; Measelle, Jeffrey R.; Laurent, Heidemarie K.; Ablow, Jennifer C.

    2013-01-01

    This study examined mothers' physiological reactivity in response to infant distress during the Still-Face Paradigm. We aimed to explore normative regulatory profiles and associated physiological and behavioral processes in order to further our understanding of what constitutes regulation in this dyadic context. We examined physiological patterns—vagal tone, indexed by respiratory sinus arrhythmia (RSA)-- while mothers maintained a neutral expression over the course of the still face episode, as well as differential reactivity patterns in mothers with depression symptoms compared to non-depressed mothers. Behavioral and physiological data were collected from mothers of 5-month-old infants during the emotion suppression phase of the Still-Face Paradigm. We used Hierarchical Linear Modeling to examine changes in mothers' RSA during infant distress and explored maternal depression as a predictor of physiological profiles. Mothers were generally able to maintain a neutral expression and simultaneously demonstrated a mean-level increase in RSA during the still face episode compared to baseline, indicating an active regulatory response overall. A more detailed time-course examination of RSA trajectories revealed that an initial RSA increase was typically followed by a decrease in response to peak infant distress, suggesting a physiological mobilization response. However, this was not true of mothers with elevated depressive symptoms, who showed no change in RSA during infant distress. These distinct patterns of infant distress-related physiological activation may help to explain differences in maternal sensitivity and adaptive parenting. PMID:23454427

  11. Attenuation of human carotid-cardiac vagal baroreflex responses after physical detraining

    Science.gov (United States)

    Convertino, Victor A.; Fritsch, Janice M.

    1992-01-01

    Astronauts who are occupied with prelaunch schedules may have to limit their regular physical exercise routines. To assess a potential effect on blood pressure control, carotid baroreceptor-cardiac reflex responses of 16 men were evaluated before and after two weeks of exercise detraining that followed ten weeks of regular scheduled exercise (30 min/d, 4 d/week at 75 percent V(O2) max). After detraining, the baroreflex stimulus-response relationship had a reduced slope 0.4 msec/mmHg and range of response. In addition, there was a resetting of the relationship on the R-R interval axis. Both the minimum and maximum R-R interval responses to the stimulus were significantly reduced after detraining. Baseline systolic pressure did not change with detraining, and the carotid baroreceptor-cardiac response relationship did not shift on the pressure axis. These results suggest that detraining from regular exercise can compromise vagally-mediated mechanisms of blood pressure regulation.

  12. Insulin signals through the dorsal vagal complex to regulate energy balance.

    Science.gov (United States)

    Filippi, Beatrice M; Bassiri, Aria; Abraham, Mona A; Duca, Frank A; Yue, Jessica T Y; Lam, Tony K T

    2014-03-01

    Insulin signaling in the hypothalamus regulates food intake and hepatic glucose production in rodents. Although it is known that insulin also activates insulin receptor in the dorsal vagal complex (DVC) to lower glucose production through an extracellular signal-related kinase 1/2 (Erk1/2)-dependent and phosphatidylinositol 3-kinase (PI3K)-independent pathway, it is unknown whether DVC insulin action regulates food intake. We report here that a single acute infusion of insulin into the DVC decreased food intake in healthy male rats. Chemical and molecular inhibition of Erk1/2 signaling in the DVC negated the acute anorectic effect of insulin in healthy rats, while DVC insulin acute infusion failed to lower food intake in high fat-fed rats. Finally, molecular disruption of Erk1/2 signaling in the DVC of healthy rats per se increased food intake and induced obesity over a period of 2 weeks, whereas a daily repeated acute DVC insulin infusion for 12 days conversely decreased food intake and body weight in healthy rats. In summary, insulin activates Erk1/2 signaling in the DVC to regulate energy balance.

  13. High cardiac vagal control is related to better subjective and objective sleep quality

    Science.gov (United States)

    Werner, Gabriela G.; Ford, Brett Q.; Mauss, Iris B.; Schabus, Manuel; Blechert, Jens; Wilhelm, Frank H.

    2015-01-01

    Cardiac vagal control (CVC) has been linked to both physical and mental health. One critical aspect of health, that has not received much attention, is sleep. We hypothesized that adults with higher CVC – operationalized by high-frequency heart rate variability (HF-HRV) – will exhibit better sleep quality assessed both subjectively (i.e., with Pittsburgh Sleep Quality Index) and objectively (i.e., with polysomnography). HF-HRV was measured in 29 healthy young women during an extended neutral film clip. Participants then underwent full polysomnography to obtain objective measures of sleep quality and HF-HRV during a night of sleep. As expected, higher resting HF-HRV was associated with higher subjective and objective sleep quality (i.e., shorter sleep latency and fewer arousals). HF-HRV during sleep (overall or separated by sleep phases) showed less consistent relationships with sleep quality. These findings indicate that high waking CVC may be a key predictor of healthy sleep. PMID:25709072

  14. Cardiac vagal tone is associated with social engagement and self-regulation.

    Science.gov (United States)

    Geisler, Fay C M; Kubiak, Thomas; Siewert, Kerstin; Weber, Hannelore

    2013-05-01

    The polyvagal theory (Porges, 2007) represents a biobehavioral model that relates autonomic functioning to self-regulation and social engagement. The aim of the two presented studies was to test the proposed association of cardiac vagal tone (CVT), assessed via resting high-frequency heart rate variability (respiratory sinus arrhythmia, RSA), with coping, emotion-regulation, and social engagement in young adults. In Study 1 (retrospective self-report), RSA was positively associated with engagement coping (situation control, response control, positive self-instructions, social-support seeking) and aspects of social well-being. In Study 2 (ecological momentary assessment), for 28 days following the initial assessment, RSA predicted less use of disengagement strategies (acceptance and avoidance) for regulating negative emotions and more use of socially adaptive emotion-regulation strategies (i.e., social-support seeking as a reaction to sadness and making a concession as a reaction to anger caused by others). Furthermore, RSA was higher in participants who reported no anger episodes compared to those who reported at least one anger episode and was positively associated with reported episodes of negative emotions. Results support the association proposed by the PVT between CVT and self-regulatory behavior, which promotes social bonds. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Vagus nerve stimulation for the treatment of refractory epilepsy

    Directory of Open Access Journals (Sweden)

    Gorgan M.R.

    2015-06-01

    Full Text Available Vagus nerve stimulation (VNS represents one of the main surgical options for the treatment of the refractory epilepsy in pediatric and adult patients. There are several mechanism involved in vagal nerve stimulation which could influence the pathophysiology of seizures like neuromodulation of the thalamic and subthalamic nuclei involved in seizure initiation and the modulation of the neurotransmitters pattern norepinefrin, GABA, and serotonin. The VNS system is composed of the implanted components (the generator, the lead with the electrodes attached and the programming system components (programming wand and handheld computer. The authors present their experience with 81 patients diagnosed with refractory epilepsy, investigated, selected and implanted with vagal neurostimulators between December 2012 and January 2015 in Neurosurgery Clinic, "Bagdasar-Arseni" Emergency Hospital. The surgical technique and the potential pitfalls are described in detail. There were 20 children (24,7% and 61 (75,3% adults in this series. There was no death in this series and no intraoperative incidence. One patient presented dysphagia postoperatively which completely remitted after two months of follow-up. The outcome in term of seizure frequency and severity was better for patients under 30 years compared with patients older than 30 years. VNS represents now a safe, quick and efficient surgical procedure with a minimum period of hospitalization and a short recovery period. The good results on long term improve the quality of life of the patients and facilitate the social and professional reinsertion

  16. Thermal detection thresholds of Aδ- and C-fibre afferents activated by brief CO2 laser pulses applied onto the human hairy skin.

    Directory of Open Access Journals (Sweden)

    Maxim Churyukanov

    Full Text Available Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO(2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C and C-fibres (39.8±1.7°C. Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.

  17. Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

    Science.gov (United States)

    Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

    2009-10-01

    Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

  18. Anal sphincter responses after perianal electrical stimulation

    DEFF Research Database (Denmark)

    Pedersen, Ejnar; Klemar, B; Schrøder, H D

    1982-01-01

    By perianal electrical stimulation and EMG recording from the external anal sphincter three responses were found with latencies of 2-8, 13-18 and 30-60 ms, respectively. The two first responses were recorded in most cases. They were characterised by constant latency and uniform pattern, were...... stimulation to a minimum of 30-60 ms. This response represented the clinical observable spinal reflex, "the classical anal reflex". The latencies of the two first responses were so short that they probably do not represent spinal reflexes. This was further supported by the effect of epidural anaesthesia which...... left the first responses unaffected but abolished the classical anal reflex. The origin of the two first responses is discussed and models involving antidromal impulse propagation in the efferent fibre as the afferent limbs of the responses are proposed....

  19. [ELECTRIC STIMULATION OF VAGUS NERVE MODULATES A PROPAGATION OF OXYGEN EPILEPSY IN RABBITS].

    Science.gov (United States)

    Zhilyaev, S Yu; Moskvin, A N; Platonova, T F; Demchenko, I T

    2015-11-01

    The activation of autonomic afferents (achieved through the vagus nerve (VN) electrical stimulation) on CNS O2 toxicity and cardiovascular function was investigated. In conscious rabbits at 5 ATA 02, prodromal signs of CNS O2 toxicity and convulsion latency were determined with and without vagus nerve (VN) stimulation. EEG, ECG and respiration were also recorded. In rabbits at 5 ATA, sympathetic overdrive and specific patterns on the EEG (synchronization of slow-waves), ECG (tachycardia) and respiration (respiratory minute volume increase) preceded motor convulsions. Vagus nerve stimulation increased parasympathetic component of autonomic drive and significantly delayed prodromal signs of oxygen toxicity and convulsion latency. Autonomic afferent input to the brain is a novel target for preventing CNS toxicity in HBO2.

  20. Role of Sensory Stimulation in Amelioration of Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Mak Adam Daulatzai

    2011-01-01

    Full Text Available Obstructive sleep apnea (OSA, characterized by recurrent upper airway (UA collapse during sleep, is associated with significant morbidity and disorders. Polysomnogram is employed in the evaluation of OSA and apnea-hypopnea number per hour reflects severity. For normal breathing, it is essential that the collapsible UA is patent. However, obstruction of the UA is quite common in adults and infants. Normally, important reflex mechanisms defend against the UA collapse. The muscle activity of UA dilators, including the genioglossus, tensor palatini (TP, and pharyngeal constrictors, is due to the integrated mechanism of afferent sensory input → to motor function. Snoring is harsh breathing to prevent UA obstruction. Unfortunately, snoring vibrations, pharyngeal suction collapse, negative pressure, and hypoxia cause pathological perturbations including dysfunctional UA afferent sensory activity. The current paper posits that peripheral sensory stimulation paradigm, which has been shown to be efficacious in improving several neurological conditions, could be an important therapeutic strategy in OSA also.

  1. Sensitization by pulmonary reactive oxygen species of rat vagal lung C-fibers: the roles of the TRPV1, TRPA1, and P2X receptors.

    Directory of Open Access Journals (Sweden)

    Ting Ruan

    Full Text Available Sensitization of vagal lung C-fibers (VLCFs induced by mediators contributes to the pathogenesis of airway hypersensitivity, which is characterized by exaggerated sensory and reflex responses to stimulants. Reactive oxygen species (ROS are mediators produced during airway inflammation. However, the role of ROS in VLCF-mediated airway hypersensitivity has remained elusive. Here, we report that inhalation of aerosolized 0.05% H2O2 for 90 s potentiated apneic responses to intravenous capsaicin (a TRPV1 receptor agonist, α,β-methylene-ATP (a P2X receptor agonist, and phenylbiguanide (a 5-HT3 receptor agonist in anesthetized rats. The apneic responses to these three stimulants were abolished by vagatomy or by perivagal capsaicin treatment, a procedure that blocks the neural conduction of VLCFs. The potentiating effect of H2O2 on the apneic responses to these VLCF stimulants was prevented by catalase (an enzyme that degrades H2O2 and by dimethylthiourea (a hydroxyl radical scavenger. The potentiating effect of H2O2 on the apneic responses to capsaicin was attenuated by HC-030031 (a TRPA1 receptor antagonist and by iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (a P2X receptor antagonist. The potentiating effect of H2O2 on the apneic responses to α,β-methylene-ATP was reduced by capsazepine (a TRPV1 receptor antagonist, and by HC-030031. The potentiating effect of H2O2 on the apneic responses to phenylbiguanide was totally abolished when all three antagonists were combined. Consistently, our electrophysiological studies revealed that airway delivery of aerosolized 0.05% H2O2 for 90 s potentiated the VLCF responses to intravenous capsaicin, α,β-methylene-ATP, and phenylbiguanide. The potentiating effect of H2O2 on the VLCF responses to phenylbiguanide was totally prevented when all antagonists were combined. Inhalation of 0.05% H2O2 indeed increased the level of ROS in the lungs. These results suggest that 1 increased lung ROS sensitizes

  2. A Little Goes a Long Way: Low Working Memory Load Is Associated with Optimal Distractor Inhibition and Increased Vagal Control under Anxiety.

    Science.gov (United States)

    Spangler, Derek P; Friedman, Bruce H

    2017-01-01

    Anxiety impairs both inhibition of distraction and attentional focus. It is unclear whether these impairments are reduced or exacerbated when loading working memory with non-affective information. Cardiac vagal control has been related to top-down regulation of anxiety; therefore, vagal control may reflect load-related inhibition of distraction under anxiety. The present study examined whether: (1) the enhancing and impairing effects of load on inhibition exist together in a non-linear function, (2) there is a similar association between inhibition and concurrent vagal control under anxiety. During anxiogenic threat-of-noise, 116 subjects maintained a digit series of varying lengths (0, 2, 4, and 6 digits) while completing a visual flanker task. The task was broken into four blocks, with a baseline period preceding each. Electrocardiography was acquired throughout to quantify vagal control as high-frequency heart rate variability (HRV). There were significant quadratic relations of working memory load to flanker performance and to HRV, but no associations between HRV and performance. Results indicate that low load was associated with relatively better inhibition and increased HRV. These findings suggest that attentional performance under anxiety depends on the availability of working memory resources, which might be reflected by vagal control. These results have implications for treating anxiety disorders, in which regulation of anxiety can be optimized for attentional focus.

  3. Decreased contribution from afferent feedback to the soleus muscle during walking in patients with spastic stroke

    DEFF Research Database (Denmark)

    Mazzaro, Nazarena; Nielsen, Jørgen Feldbæk; Grey, Michael James

    2007-01-01

    We investigated the contribution of afferent feedback to the soleus (SOL) muscle activity during the stance phase of walking in patients with spastic stroke. A total of 24 patients with hemiparetic spastic stroke and age-matched healthy volunteers participated in the study. A robotic actuator...... attached to the foot and leg was used to apply 3 types of ankle perturbations during treadmill walking. First, fast dorsiflexion perturbations were applied to elicit stretch reflexes in the SOL muscle. The SOL short-latency stretch reflex was facilitated in the patients (1.4 +/- 0.3) compared...... with the healthy volunteers (1.0 +/- 0.3, P = .05). Second, fast plantar flexion perturbations were applied during the stance phase to unload the plantar flexor muscles, thus, removing the afferent input from these muscles to the SOL motoneurons. These perturbations produced a distinct decrease in SOL activity...

  4. [Sensory afferences and motor control of equilibrium using static and dynamic posture tests].

    Science.gov (United States)

    Perrin, P; Perrin, C

    1996-01-01

    One thousand two hundred posturographic tests have been performed since 1988 at the Laboratoire d'Exploration Fonctionnelle ORL, Centre Hospitalier Universitaire, Nancy-Brabois, using three complementary protocols (Toennis GmBh, G). Static tests [1] measure over 20 seconds periods the displacement of the center of foot pressure (CFP) on individual standing upright on the platform. Dynamic tests assess the mechanisms of balance control following measured platform movements, using surface EMG after a single sharp and unexpected tilt [2], or CFP displacements during longer regular oscillations of the platform [3]. The latter test enables an analysis of balance strategy adopted to maintain equilibrium. These three programs were applied to series of children, adults, elderly people, sportsmen, and patients suffering from ENT, neurological or traumatic disorders. They were confirmed to be complementary tests allowing a thorough investigation of all balance control mechanisms: visual afferences [1], somesthesy [2] and the combination of visual, somesthetic and vestibular afferences in the third test.

  5. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

    DEFF Research Database (Denmark)

    Oppermann, Mona; Hansen, Pernille B; Castrop, Hayo

    2007-01-01

    Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or N......(G)-nitro-L-arginine methyl ester, furosemide caused a dose-dependent increase of vascular diameter, but it was without effect in vessels from NKCC1-/- mice suggesting that inhibition of NKCC1 mediates dilatation in afferent arterioles. In the intact kidney, however, furosemide (2 mg/kg iv) caused a 50.5 +/- 3% reduction...... of total renal blood flow (RBF) and a 27% reduction of superficial blood flow (SBF) accompanied by a marked and immediate increase of tubular pressure and volume. At 10 mg/kg, furosemide reduced RBF by 60.4 +/- 2%. Similarly, NKCC1-/- mice responded to furosemide with a 45.4% decrease of RBF and a 29...

  6. Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex sensitivity in diabetic rats.

    Science.gov (United States)

    do Carmo, Jussara M; Hall, John E; da Silva, Alexandre A

    2008-11-01

    This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 +/- 17 mg/dl) and bradycardia (-79 +/- 4 beats/min). Leptin decreased glucose levels (165 +/- 16 mg/dl) and raised HR to control values (303 +/- 10 to 389 +/- 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 +/- 7 vs. 316 +/- 6, -19 +/- 2 vs. -43 +/- 6, and 39 +/- 3 vs. 68 +/- 8 beats/min), and leptin treatment restored these variables to normal (300 +/- 7, -68 +/- 10, and 71 +/- 8 beats/min). Leptin normalized BRS (bradycardia, -2.6 +/- 0.3, -1.7 +/- 0.2, and -3.0 +/- 0.5; and tachycardia, -3.2 +/- 0.4, -1.9 +/- 0.3, and -3.4 +/- 0.3 beats.min(-1).mmHg(-1) for control, diabetes, and leptin) and HR variability (23 +/- 4 to 11 +/- 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.

  7. Gender Differences in Histamine-Induced Depolarization and Inward Currents in Vagal Ganglion Neurons in Rats

    Science.gov (United States)

    Li, Jun-Nan; Qian, Zhao; Xu, Wen-Xiao; Xu, Bing; Lu, Xiao-Long; Yan, Zhen-Yu; Han, Li-Min; Liu, Yang; Yuan, Mei; Schild, John; Qiao, Guo-Fen; Li, Bai-Yan

    2013-01-01

    Evidence has shown gender differences regarding the critical roles of histamine in the prevalence of asthma, anaphylaxis, and angina pectoris. Histamine depolarizes unmyelinated C-type neurons without any effects on myelinated A-type vagal ganglion neurons (VGNs) in male rats. However, little is known if VGNs from females react to histamine in a similar manner. Membrane depolarization and inward currents were tested in VGNs isolated from adult rats using a whole-cell patch technique. Results from males were consistent with the literature. Surprisingly, histamine-induced depolarization and inward currents were observed in both unmyelinated C-type and myelinated A- and Ah-type VGNs from female rats. In Ah-type neurons, responses to 1.0 μM histamine were stronger in intact females than in males and significantly reduced in ovariectomized (OVX) females. In C-type neurons, histamine-induced events were significantly smaller (pA/pF) in intact females compared with males and this histamine-induced activity was dramatically increased by OVX. Female A-types responded to histamine, which was further increased following ovariectomy. Histamine at 300 nM depolarized Ah-types in females, but not Ah-types in OVX females. In contrast, the sensitivity of A- and C-types to histamine was upregulated by OVX. These data demonstrate gender differences in VGN chemosensitivity to histamine for the first time. Myelinated Ah-types showed the highest sensitivity to histamine across female populations, which was changed by OVX. These novel findings improve the understanding of gender differences in the prevalence of asthma, anaphylaxis, and pain. Changes in sensitivity to histamine by OVX may explain alterations in the prevalence of certain pathophysiological conditions when women reach a postmenopausal age. PMID:24339729

  8. Regulation of Piezo2 Mechanotransduction by Static Plasma Membrane Tension in Primary Afferent Neurons.

    Science.gov (United States)

    Jia, Zhanfeng; Ikeda, Ryo; Ling, Jennifer; Viatchenko-Karpinski, Viacheslav; Gu, Jianguo G

    2016-04-22

    The Piezo2 channel is a newly identified mammalian mechanical transducer that confers rapidly adapting mechanically activated (RA-MA) currents in primary afferent neurons. The Piezo2 channels sense rapid membrane displacement, but it is not clear whether they are sensitive to osmotic swelling, which slowly increases static plasma membrane tension (SPMT). Here, we show that SPMT exerts a profound impact on the mechanical sensitivity of RA-MA channels in primary afferent neurons. RA-MA currents are greatly enhanced, and the mechanical threshold was reduced in both primary afferent neurons of rat dorsal root ganglia (DRG) and HEK293 cells heterologously expressing Piezo2 when these cells undergo osmotic swelling to increase SPMT. Osmotic swelling switches the kinetics of RA-MA currents to the slowly adapting type in both cultured DRG neurons and HEK293 cells heterologously expressing Piezo2. The potentiation of RA-MA currents is abolished when cultured DRG neurons are treated with cytochalasin D, an actin filament disruptor that prevents SPMT of cultured DRG neurons from an increase by osmotic swelling. Osmotic swelling significantly increases DRG neuron mechano-excitability such that a subthreshold mechanical stimulus can result in action potential firing. Behaviorally, the mechanical hind paw withdrawal threshold in rats is reduced following the injection of a hypotonic solution, but this osmotic effect is abolished when cytochalasin D or Gd(3+) is co-administered with the hypo-osmotic solution. Taken together, our findings suggest that Piezo2-mediated mechanotransduction is regulated by SPMT in primary afferent neurons. Because SPMT can be changed by multiple biological factors, our findings may have broad implications in mechanical sensitivity under physiological and pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Fine motor control of the jaw following alteration of orofacial afferent inputs.

    Science.gov (United States)

    Kumar, Abhishek; Castrillon, Eduardo; Trulsson, Mats; Svensson, Krister G; Svensson, Peter

    2017-03-01

    The study was designed to investigate if alteration of different orofacial afferent inputs would have different effects on oral fine motor control and to test the hypothesis that reduced afferent inputs will increase the variability of bite force values and jaw muscle activity, and repeated training with splitting of food morsel in conditions with reduced afferent inputs would decrease the variability and lead to optimization of bite force values and jaw muscle activity. Forty-five healthy volunteers participated in a single experimental session and were equally divided into incisal, mucosal, and block anesthesia groups. The participants performed six series (with ten trials) of a standardized hold and split task after the intervention with local anesthesia was made in the respective groups. The hold and split forces along with the corresponding jaw muscle activity were recorded and compared to a reference group. The hold force and the electromyographic (EMG) activity of the masseter muscles during the hold phase were significantly higher in the incisal and block anesthesia group, as compared to the reference group (P motor control. Further, inhibition of afferent inputs from the orofacial or periodontal mechanoreceptors did not increase the variability of bite force values and jaw muscle activity; indicating that the relative precision of the oral fine motor task was not compromised inspite of the anesthesia. The results also suggest the propensity of optimization of bite force values and jaw muscle activity due to repeated splitting of the food morsels, inspite of alteration of sensory inputs. Skill acquisition following a change in oral sensory environment is crucial for understanding how humans learn and re-learn oral motor behaviors and the kind of adaptation that takes place after successful oral rehabilitation procedures.

  10. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    Science.gov (United States)

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

  11. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    OpenAIRE

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.; Gebhart, G.F.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined chann...

  12. Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

    DEFF Research Database (Denmark)

    Grey, Michael James; Ladouceur, Michel; Andersen, Jacob B.

    2001-01-01

    component (P = 0.004), whereas the medium latency component was unchanged (P = 0.437). 6. Two hours after the ingestion of tizanidine, an alpha(2)-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P...... the hypothesis that, during walking the medium latency component of the stretch reflex resulting from an unexpected perturbation is contributed to by group II muscle afferents....

  13. Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy123

    Science.gov (United States)

    Reyes, Beverly A. S.; Zitnik, Gerard; Foster, Celia; Van Bockstaele, Elisabeth J.

    2015-01-01

    Abstract Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident–intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies. PMID:26634226

  14. The effect of type of afferent feedback timed with motor imagery on the induction of cortical plasticity

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Voigt, Michael; Stevenson, Andrew James Thomas

    2017-01-01

    A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer......A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain...

  15. Local activation of cannabinoid CB1 receptors in the urinary bladder reduces the inflammation-induced sensitization of bladder afferents

    Directory of Open Access Journals (Sweden)

    Cervero Fernando

    2011-05-01

    Full Text Available Abstract Background Systemic administration of cannabinoid agonists is known to reduce pain induced by bladder inflammation and to modulate cystometric parameters in vivo. We have previously reported that intravesical administration of a cannabinoid agonist reduces the electrical activity of bladder afferents under normal conditions. However, the effects of local activation of bladder cannabinoid receptors on afferent activity during inflammation are unknown. This study was aimed to assess the effects of intravesical administration of a cannabinoid agonist on the discharges of afferent fibers in inflamed bladders ex vivo. We also characterized the expression of CB1 receptors in the bladder and their localization and co-expression with TRPV1, a marker of nociceptive afferents. Results Compared to untreated animals, afferent fiber activity in inflamed bladders was increased for intravesical pressures between 10 and 40 mmHg. Local treatment with a non selective cannabinoid agonist (AZ12646915 significantly reduced the afferent activity at intravesical pressures above 20 mmHg. This effect was blocked by AM251 but not by AM630 (selective for CB1 and CB2 respectively. Finally, CB1 was co-expressed with TRPV1 in control and inflamed bladders. Conclusion These results demonstrate that sensitization of bladder afferents induced by inflammation is partly suppressed by intravesical activation of cannabinoid receptors, an effect that appears to be mediated by CB1 receptors. Also, TRPV1 positive fibers were found to co-express CB1, supporting the hypothesis of a direct action of the cannabinoid agonist on nociceptive afferents. Taken together, these results indicate a peripheral modulation by the cannabinoid system of bladder hypersensitivity during inflammation.

  16. Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents

    OpenAIRE

    Tanaka, T.; Shinoda, M.; Feng, B.; Albers, K. M.; Gebhart, G. F.

    2010-01-01

    Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersen...

  17. The renal nerves in chronic heart failure: efferent and afferent mechanisms

    Science.gov (United States)

    Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

    2015-01-01

    The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

  18. The Renal Nerves in Chronic Heart Failure: Afferent and Efferent Mechanisms

    Directory of Open Access Journals (Sweden)

    Alicia Marie Schiller

    2015-08-01

    Full Text Available The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF. Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent

  19. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear

    Science.gov (United States)

    Mendus, Diana; Sundaresan, Srividya; Grillet, Nicolas; Wangsawihardja, Felix; Leu, Rose; Müller, Ulrich; Jones, Sherri M.; Mustapha, Mirna

    2014-01-01

    Thrombospondins (TSPs) are a family of secreted extracellular matrix proteins that have been shown to be involved in the formation of synapses in the central nervous system. In this study, we show that TSP1 and TSP2 are expressed in the cochlea, and offer the first description of their putative roles in afferent synapse development and function in the inner ear. We examined mice with deletions of TSP1, TSP2, and both (TSP1/2), for inner ear development and function. Immunostaining for synaptic markers indicated a significant decrease in the number of formed afferent synapses in the cochlea of TSP2 and TSP1/2 knockout (KO) mice at P29. In functional studies, TSP2 and TSP1/2 KO mice showed elevated auditory brainstem response (ABR) thresholds compared to wild type littermates starting at postnatal (P) day 15 with the most severe phenotype for the TSP1/2 KO mice. TSP1/2 KO mice also showed reduced wave I amplitudes of ABR and vestibular evoked potential suggesting a synaptic dysfunction in both the auditory and vestibular systems. While ABR thresholds in TSP1 KO mice were relatively unaffected at early ages, TSP1/2 double mutants exhibited the most severe phenotype among all the genotypes tested, suggesting functional redundancy between these two genes. Based on the above results, we propose that TSPs play an important role in afferent synapse development and function of the inner ear. PMID:24460873

  20. Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle afferent DRG neurons.

    Science.gov (United States)

    Lin, Yi-Wen; Chen, Chih-Cheng

    2015-01-01

    Muscle afferent neurons that express transient receptor potential vanilloid type I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle nociceptors plays an important role in the acid-induced hyperalgesic priming and the development of chronic hyperalgesia in a mouse model of fibromyalgia. To understand the electrophysiological properties of the TRPV1-expressing muscle afferent neurons, we used whole-cell patch clamp recording to study the acid responsiveness and action potential (AP) configuration of capsaicin-sensitive neurons innervating to gastrocnemius muscle. Here we showed that IB4-negative TRPV1-expressing muscle afferent neurons are heterogeneous in terms of cell size, resting membrane potential, AP configuration, tetrodotoxin (TTX)-resistance, and acid-induced current (I acid), as well as capsaicin-induced current (I cap). TRPV1-expressing neurons were all acid-sensitive and could be divided into two acid-sensitive groups depending on an acid-induced sustained current (type I) or an acid-induced biphasic ASIC3-like current (type II). Type I TRPV1-expressing neurons were distinguishable from type II TRPV1-expressing neurons in AP overshoot, after-hyperpolarization duration, and all I acid parameters, but not in AP threshold, TTX-resistance, resting membrane potential, and I cap parameters. These differential biophysical properties of TRPV1-expressing neurons might partially annotate their different roles involved in the development and maintenance of chronic muscle pain.

  1. Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation induced by acute hypernatremia.

    Science.gov (United States)

    Silva, Elaine F; Sera, Celisa T N; Mourão, Aline A; Lopes, Paulo R; Moreira, Marina C S; Ferreira-Neto, Marcos L; Colombari, Débora A S; Cravo, Sérgio L D; Pedrino, Gustavo R

    2015-11-01

    Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short-term regulation of blood pressure and detection of variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P hypernatremia. © 2015 Wiley Publishing Asia Pty Ltd.

  2. A DSP for sensing the bladder volume through afferent neural pathways.

    Science.gov (United States)

    Mendez, Arnaldo; Belghith, Abrar; Sawan, Mohamad

    2014-08-01

    In this paper, we present a digital signal processor (DSP) capable of monitoring the urinary bladder volume through afferent neural pathways. The DSP carries out real-time detection and can discriminate extracellular action potentials, also known as on-the-fly spike sorting. Next, the DSP performs a decoding method to estimate either three qualitative levels of fullness or the bladder volume value, depending on the selected output mode. The proposed DSP was tested using both realistic synthetic signals with a known ground-truth, and real signals from bladder afferent nerves recorded during acute experiments with animal models. The spike sorting processing circuit yielded an average accuracy of 92% using signals with highly correlated spike waveforms and low signal-to-noise ratios. The volume estimation circuits, tested with real signals, reproduced accuracies achieved by offline simulations in Matlab, i.e., 94% and 97% for quantitative and qualitative estimations, respectively. To assess feasibility, the DSP was deployed in the Actel FPGA Igloo AGL1000V2, which showed a power consumption of 0.5 mW and a latency of 2.1 ms at a 333 kHz core frequency. These performance results demonstrate that an implantable bladder sensor that perform the detection, discrimination and decoding of afferent neural activity is feasible.

  3. Role of the vagus nerve in the development and treatment of diet‐induced obesity

    Science.gov (United States)

    2016-01-01

    Abstract This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie‐rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high‐fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade‐induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity. PMID:26959077

  4. Role of the vagus nerve in the development and treatment of diet-induced obesity.

    Science.gov (United States)

    de Lartigue, Guillaume

    2016-10-15

    This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie-rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high-fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade-induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  5. [Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

    Science.gov (United States)

    Xue, Run-Qing; Xu, Man; Yu, Xiao-Jiang; Liu, Long-Zhu; Zang, Wei-Jin

    2017-10-25

    Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

  6. growth stimulant

    African Journals Online (AJOL)

    Effects of timing and duration of supplementation of LIVFIT VET ® (growth stimulant) as substitute for fish meal on the growth performance, haematology and clinical enzymes concentration of growing pigs.

  7. Hand muscle reflexes following air puff stimulation.

    Science.gov (United States)

    Deuschl, G; Feifel, E; Guschlbauer, B; Lücking, C H

    1995-01-01

    Hand muscle reflexes following muscle stretch and electrical nerve stimulation show a typical pattern consisting of short- and long-latency reflexes. The present investigation was designed to test reflexes following pure cutaneous stimulation. Air puffs were delivered to the palmar tip and the nail bed of the first, second and fifth fingers during isotonic contraction of hand muscles. The EMGs from the thenar muscles, the first dorsal interosseous muscle and the hypothenar muscles were recorded. Reflexes were obtained in all muscles, with a typical configuration consisting of a short-latency excitatory component (cutaneous long-latency reflex I, cLLR I) and a second excitatory component (cutaneous long-latency reflex II, cLLR II), with an inhibitory component between them. The size of cLLR II differed depending on the area stimulated and the muscle recorded. We found the largest responses always in the muscle acting on the stimulated finger. The reflex size depended on the strength of air puff stimulation. Allowing small displacements of the fingers led to an additional increase in the size of the reflex. The pattern of reflexes was identical independent of whether the finger tip or the nail bed was stimulated, but the size of the reflexes was smaller following nail bed stimulation. Following blockade of the cutaneous nerve branches of the thumb with local anaesthetics, air puff stimulation of the thumb no longer elicited this reflex pattern. Hence, under our experimental conditions, cutaneous receptors were the only source of afferent input for these reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions.

    Science.gov (United States)

    Makovac, Elena; Garfinkel, Sarah N; Bassi, Andrea; Basile, Barbara; Macaluso, Emiliano; Cercignani, Mara; Calcagnini, Giovanni; Mattei, Eugenio; Agalliu, Daniela; Cortelli, Pietro; Caltagirone, Carlo; Bozzali, Marco; Critchley, Hugo

    2015-06-01

    Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.

  9. The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics.

    Science.gov (United States)

    Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens

    2017-03-01

    Analysis of heart rate variability (HRV) by nonlinear approaches has been gaining interest due to their ability to extract additional information from heart rate (HR) dynamics that are not detectable by traditional approaches. Nevertheless, the physiological interpretation of nonlinear approaches remains unclear. Therefore, we propose long-term (60 min) protocols involving selective blockade of cardiac autonomic receptors to investigate the contribution of sympathetic and parasympathetic function upon nonlinear dynamics of HRV. Conscious male Wistar rats had their electrocardiogram (ECG) recorded under three distinct conditions: basal, selective (atenolol or atropine), or combined (atenolol plus atropine) pharmacological blockade of autonomic muscarinic or β1-adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE1-5) and long (6 to 30, MSE6-30) time scales was computed, as well as DFA scaling exponents at short (αshort, 5 ≤ n ≤ 15), mid (αmid, 30 ≤ n ≤ 200), and long (αlong, 200 ≤ n ≤ 1,700) window sizes. The results show that MSE1-5 is reduced under atropine blockade and MSE6-30 is reduced under atropine, atenolol, or combined blockade. In addition, while atropine expressed its maximal effect at scale six, the effect of atenolol on MSE increased with scale. For DFA, αshort decreased during atenolol blockade, while the αmid increased under atropine blockade. Double blockade decreased αshort and increased αlong Results with surrogate data show that the dynamics during combined blockade is not random. In summary, sympathetic and vagal control differently affect entropy (MSE) and fractal properties (DFA) of HRV. These findings are important to guide future studies.NEW & NOTEWORTHY Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological

  10. Vibrotactile stimulation of fast-adapting cutaneous afferents from the foot modulates proprioception at the ankle joint.

    Science.gov (United States)

    Mildren, Robyn L; Bent, Leah R

    2016-04-15

    It has previously been shown that cutaneous sensory input from across a broad region of skin can influence proprioception at joints of the hand. The present experiment tested whether cutaneous input from different skin regions across the foot can influence proprioception at the ankle joint. The ability to passively match ankle joint position (17° and 7° plantar flexion and 7° dorsiflexion) was measured while cutaneous vibration was applied to the sole (heel, distal metatarsals) or dorsum of the target foot. Vibration was applied at two different frequencies to preferentially activate Meissner's corpuscles (45 Hz, 80 μm) or Pacinian corpuscles (255 Hz, 10 μm) at amplitudes ∼3 dB above mean perceptual thresholds. Results indicated that cutaneous input from all skin regions across the foot could influence joint-matching error and variability, although the strongest effects were observed with heel vibration. Furthermore, the influence of cutaneous input from each region was modulated by joint angle; in general, vibration had a limited effect on matching in dorsiflexion compared with matching in plantar flexion. Unlike previous results in the upper limb, we found no evidence that Pacinian input exerted a stronger influence on proprioception compared with Meissner input. Findings from this study suggest that fast-adapting cutaneous input from the foot modulates proprioception at the ankle joint in a passive joint-matching task. These results indicate that there is interplay between tactile and proprioceptive signals originating from the foot and ankle. Copyright © 2016 the American Physiological Society.

  11. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    Science.gov (United States)

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  12. Infant diet, gender and the development of vagal tone stability during the first two years of life.

    Science.gov (United States)

    Pivik, R T; Andres, Aline; Tennal, Kevin B; Gu, Yuyuan; Cleves, Mario A; Badger, Thomas M

    2015-05-01

    Postnatal nutrition influences neurodevelopment, but it is not known whether the development of individual differences in physiologic measures is related to variations in early postnatal diet. To address this issue we studied the stability of vagal tone (V)--an index of individual differences in parasympathetic heart rate control-by measuring resting V quarterly during infancy and again at 2 years in 146 breast-fed (BF), 143 milk formula-fed (MF), and 137 soy formula-fed (SF) infants. Stability of V across infancy was more consistently significant for BF than formula-fed infants. Stability was similar for boys and girls in BF and SF groups but was generally higher in boys than girls in the MF group. Significant stability between infancy and 2 years emerged later in SF than other groups and later in boys than girls. Stability generally peaked between 6 and 9 months-a time when postnatal vagal myelination slows and which may represent a pivotal stage in the development of V stability. These findings indicate that infant diet and gender are important modulators of the early development of autonomic state control. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Heritability of cardiac vagal control in 24-h heart rate variability recordings: influence of ceiling effects at low heart rates.

    Science.gov (United States)

    Neijts, Melanie; Van Lien, Rene; Kupper, Nina; Boomsma, Dorret; Willemsen, Gonneke; de Geus, Eco J C

    2014-10-01

    This study estimated the heritability of 24-h heart rate variability (HRV) measures, while considering ceiling effects on HRV at low heart rates during the night. HRV was indexed by the standard deviation of all valid interbeat intervals (SDNN), the root mean square of differences between valid, successive interbeat intervals (RMSSD), and peak-valley respiratory sinus arrhythmia (pvRSA). Sleep and waking levels of cardiac vagal control were assessed in 1,003 twins and 285 of their non-twin siblings. Comparable heritability estimates were found for SDNN (46%-53%), RMSSD (49%-54%), and pvRSA (48%-57%) during the day and night. A nighttime ceiling effect was revealed in 10.7% of participants by a quadratic relationship between mean pvRSA and the interbeat interval. Excluding these participants did not change the heritability estimates. The genetic factors influencing ambulatory pvRSA, RMSSD, and SDNN largely overlap. These results suggest that gene-finding studies may pool the different cardiac vagal indices and that exclusion of participants with low heart rates is not required. Copyright © 2014 Society for Psychophysiological Research.

  14. Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.

    Science.gov (United States)

    Di Lazzaro, V; Oliviero, A; Pilato, F; Saturno, E; Dileone, M; Marra, C; Daniele, A; Ghirlanda, S; Gainotti, G; Tonali, P A

    2004-04-01

    Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits. We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals. The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = -0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine. The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the

  15. Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats

    NARCIS (Netherlands)

    Bojovic, Ognjen; Panja, Deb; Bittins, Margarethe; Bramham, Clive R.; Tjolsen, Arne

    2015-01-01

    Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary

  16. Surgical approaches to treatment of gastroparesis: gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes.

    Science.gov (United States)

    Sarosiek, Irene; Davis, Brian; Eichler, Evelin; McCallum, Richard W

    2015-03-01

    Gastric electrical stimulation (GES) is neurostimulation; its mechanism of action is affecting central control of nausea and vomiting and enhancing vagal function. GES is a powerful antiemetic available for patients with refractory symptoms of nausea and vomiting from gastroparesis of idiopathic and diabetic causes. GES is not indicated as a way of reducing abdominal pain in gastroparetic patients. The need for introducing a jejunal feeding tube means intensive medical therapies are failing, and is an indication for the implantation of the GES system, which should always be accompanied by a pyloroplasty to guarantee accelerated gastric emptying. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Vagus nerve stimulator in patients with epilepsy: indications and recommendations for use

    Directory of Open Access Journals (Sweden)

    Vera C Terra

    2013-11-01

    Full Text Available Epilepsy comprises a set of neurologic and systemic disorders characterized by recurrent spontaneous seizures, and is the most frequent chronic neurologic disorder. In patients with medically refractory epilepsy, therapeutic options are limited to ablative brain surgery, trials of experimental antiepileptic drugs, or palliative surgery. Vagal nerve stimulation is an available palliative procedure of which the mechanism of action is not understood, but with established efficacy for medically refractory epilepsy and low incidence of side-effects. In this paper we discuss the recommendations for VNS use as suggested by the Brazilian League of Epilepsy and the Scientific Department of Epilepsy of the Brazilian Academy of Neurology Committee of Neuromodulation.

  18. EXPRESS: Voltage-dependent sodium (NaV) channels in group IV sensory afferents.

    Science.gov (United States)

    Ramachandra, Renuka; Elmslie, Keith S

    2016-01-01

    Patients with intermittent claudication suffer from both muscle pain and an exacerbated exercise pressor reflex. Excitability of the group III and group IV afferent fibers mediating these functions is controlled in part by voltage-dependent sodium (NaV) channels. We previously found tetrodotoxin-resistant NaV1.8 channels to be the primary type in muscle afferent somata. However, action potentials in group III and IV afferent axons are blocked by TTX, supporting a minimal role of NaV1.8 channels. To address these apparent differences in NaV channel expression between axon and soma, we used immunohistochemistry to identify the NaV channels expressed in group IV axons within the gastrocnemius muscle and the dorsal root ganglia sections. Positive labeling by an antibody against the neurofilament protein peripherin was used to identify group IV neurons and axons. We show that >67% of group IV fibers express NaV1.8, NaV1.6, or NaV1.7. Interestingly, expression of NaV1.8 channels in group IV somata was significantly higher than in the fibers, whereas there were no significant differences for either NaV1.6 or NaV1.7. When combined with previous work, our results suggest that NaV1.8 channels are expressed in most group IV axons, but that, under normal conditions, NaV1.6 and/or NaV1.7 play a more important role in action potential generation to signal muscle pain and the exercise pressor reflex.

  19. Transcutaneous vagus nerve stimulation (tVNS) modulates flow experience.

    Science.gov (United States)

    Colzato, Lorenza S; Wolters, Gina; Peifer, Corinna

    2017-11-11

    Flow has been defined as a pleasant psychological state that people experience when completely absorbed in an activity. Previous correlative evidence showed that the vagal tone (as indexed by heart rate variability) is a reliable marker of flow. So far, it has not yet been demonstrated that the vagus nerve plays a causal role in flow. To explore this we used transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique that increases activation of the locus coeruleus (LC) and norepinephrine release. A sham/placebo-controlled, randomized cross-over within-subject design was employed to infer a causal relation between the stimulated vagus nerve and flow as measured using the Flow Short-Scale in 32 healthy young volunteers. In both sessions, while being stimulated, participants had to rate their flow experience after having performed a task for 30 min. Active tVNS, compared to sham stimulation, decreased flow (as indexed by absorption scores). The results can be explained by the network reset theory, which assumes that high-phasic LC activity promotes a global reset of attention over exploitation of the current focus of attention, allowing rapid behavioral adaptation and resulting in decreased absorption scores. Furthermore, our findings corroborate the hypothesis that the vagus nerve and noradrenergic system are causally involved in flow.

  20. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  1. Excitatory actions of GABA in developing chick vestibular afferents: effects on resting electrical activity.

    Science.gov (United States)

    Cortes, Celso; Galindo, Fabian; Galicia, Salvador; Cebada, Jorge; Flores, Amira

    2013-07-01

    The aim of this study was to characterize the effect of γ-aminobutyric acid (GABA) in the resting multiunit activity of the vestibular afferents during development using the isolated inner ear of embryonic and postnatal chickens (E15-E21 and P5). GABA (10(-3) to 10(-5) M; n = 133) and muscimol (10(-3) M) elicited an increase in the frequency of the basal discharge of the vestibular afferents. We found that GABA action was dose-dependent and inversely related to animal age. Thus, the largest effect was observed in embryonic ages such as E15 and E17 and decreases in E21 and P5. The GABAA receptor antagonists, bicuculline (10(-5) M; n = 10) and picrotoxin (10(-4) M; n = 10), significantly decreased the excitatory action of GABA and muscimol (10(-3) M). Additionally, CNQX 10(-6) M, MCPG 10(-5) M and 7ClKyn 10(-5) M (n = 5) were co-applied by bath substitution (n = 5). Both the basal discharge and the GABA action significantly decreased in these experimental conditions. The chloride channel blocker 9-AC 0.5 mM produced an important reduction in the effect of GABA 10(-3) (n = 5) and 10(-4) M (n = 5). Thus, our results suggest an excitatory role of GABA in the resting activity of the vestibular afferents that can be explained by changes in the gradient of concentration of Cl(-) during development. We show for the first time that the magnitude of this GABA effect decreases at later stages of embryonic and early postnatal development. Taking into account the results with glutamatergic antagonists, we conclude that GABA has a presynaptic action but is not the neurotransmitter in the vestibular afferent synapses, although it could act as a facilitator of the spontaneous activity and may regulate glutamate release. Copyright © 2013 Wiley Periodicals, Inc.

  2. Group Ia afferents contribute to short-latency interlimb reflexes in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

    2017-01-01

    to contralateral motor neurons in humans (Stubbs & Mrachacz-Kersting, JNeurophysiol., 2009; Jankowska, Brain Res. Rev., 2008). Significance Statement: This study provides further indirect evidence for the presence of spinal commissural interneurons relaying ipsilateral sensory information to contralateral motor......, and facilitatory following flexion perturbations. Due to the onset latency (45 ms), spinal pathways likely mediate the reflexes. Furthermore, the same population of cBF motor units (MUs) inhibited following iKnee extension perturbations were facilitated following iKnee flexion perturbations, indicating...... neurons in humans, with primary contributions from group Ia muscle spindle afferents....

  3. Autonomic control of heart rate by metabolically sensitive skeletal muscle afferents in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Seifert, Thomas; Hartwich, Doreen

    2010-01-01

    Isolated activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) using post-exercise ischaemia (PEI) following handgrip partially maintains exercise-induced increases in arterial blood pressure (BP) and muscle sympathetic nerve activity (SNA), while heart rate (HR...... of cardiac parasympathetic reactivation on heart rate....... moderate (PEI-M) and high (PEI-H) intensity isometric handgrip performed at 25% and 40% maximum voluntary contraction, under control (no drug), parasympathetic blockade (glycopyrrolate) and beta-adrenergic blockade (metoprolol or propranalol) conditions, while beat-to-beat HR and BP were continuously...

  4. Using the Native Afferent Nervous System to Sense Bladder Fullness: State of the Art.

    Science.gov (United States)

    Tennyson, Lauren E; Tai, Changfeng; Chermansky, Christopher J

    2016-12-01

    The regulation of micturition involves complex neurophysiologic pathways, and its understanding has grown immensely over the past decade. Alternative approaches and applied technologies in the treatment of bladder dysfunction have minimized the complications that result from neurogenic bladder. The use of natural bladder mechanoreceptors and electroneneurographic (ENG) signal recordings from afferent nerves to chronically monitor bladder volume is a promising concept, but the technology to accomplish this has proven to be a great biomedical engineering challenge. The focus of this paper will be to describe the current state of ENG signal recording as a method to detect bladder fullness.

  5. Effect of Low-Level Laser Stimulation on EEG

    Directory of Open Access Journals (Sweden)

    Jih-Huah Wu

    2012-01-01

    Full Text Available Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

  6. Event-related cross-correlations between spike trains illustrated on interactions between motor units and muscle spindle afferents.

    Science.gov (United States)

    Windhorst, U; Koehler, W; Schwarz, C

    1987-02-01

    A method is presented for computing correlation coefficients of two (or more) output spike trains in temporal relation to one (or more) input even trains. These event-related correlation functions are computed by convolving the output spike trains, represented as point processes, with rectangular pulses of selectable width, and by then calculating linear correlation coefficients for the pairs of amplitude values obtained from the two convolved processes in temporal relation to the input events. The merits of this technique are illustrated on stimulus trains delivered to motor units (MUs) and output spike trains recorded from muscle spindle afferents of the same cat hindlimb muscle. The correlation functions obtained show the temporal course of the correlated firings of the two afferents (mostly Ia afferents from primary muscle spindle endings) as a function of time from MU activation; they are compared with the conventional cross-correlation histograms (CCHs) between afferents and with peri-stimulus time histograms (PSTHs) between stimulus and afferent firing patterns. Stimulus-related cross-correlation functions as displayed here can be calculated for any three spike trains. Possible extensions of the method to larger numbers of input and output channels are also discussed.

  7. Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses

    Science.gov (United States)

    Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T.; Wangsawihardja, Felix; Ricci, Anthony J.; Mustapha, Mirna

    2016-01-01

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. PMID:26386265

  8. Conditional Electrical Stimulation in Animal and Human Models for Neurogenic Bladder: Working Toward a Neuroprosthesis.

    Science.gov (United States)

    Powell, C R

    2016-12-01

    Sacral neuromodulation has had a tremendous impact on the treatment of urinary incontinence and lower urinary tract symptoms for patients with neurologic conditions. This stimulation does not use real-time data from the body or input from the patient. Incorporating this is the goal of those pursuing a neuroprosthesis to enhance bladder function for these patients. Investigators have demonstrated the effectiveness of conditional (also called closed-loop) feedback in animal models as well as limited human studies. Dorsal genital nerve, pudendal nerve, S3 afferent nerve roots, S1 and S2 ganglia have all been used as targets for stimulation. Most of these have also been used as sources of afferent nerve information using sophisticated nerve electrode arrays and filtering algorithms to detect significant bladder events and even to estimate the fullness of the bladder. There are problems with afferent nerve sensing, however. Some of these include sensor migration and low signal to noise ratios. Implantable pressure sensors have also been investigated that have their own unique challenges, such as erosion and sensor drift. As technology improves, an intelligent neuroprosthesis with the ability to sense significant bladder events and stimulate as needed will evolve.

  9. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  10. Improvements in well-being and vagal tone following a yogic breathing-based life skills workshop in young adults: Two open-trial pilot studies

    Directory of Open Access Journals (Sweden)

    Michael R Goldstein

    2016-01-01

    Conclusions: These findings suggest that a life skills workshop integrating yogic breathing techniques may provide self-empowering tools for enhancing well-being in young adults. Future research is indicated to further explore these effects, particularly in regards to vagal tone and other aspects of stress physiology.

  11. Heightened vagal activity during high-calorie food presentation in obese compared with non-obese individuals--results of a pilot study.

    Science.gov (United States)

    Udo, Tomoko; Weinberger, Andrea H; Grilo, Carlos M; Brownell, Kelly D; DiLeone, Ralph J; Lampert, Rachel; Matlin, Samantha L; Yanagisawa, Katherine; McKee, Sherry A

    2014-01-01

    Eating behaviours are highly cue-dependent. Changes in mood states and exposure to palatable food both increase craving and consumption of food. Vagal activity supports adaptive modulation of physiological arousal and has an important role in cue-induced appetitive behaviours. Using high-frequency heart rate variability (HF HRV), this preliminary study compared vagal activity during positive and negative mood induction, and presentation of preferred high-calorie food items between obese (n = 12; BMI ≥ 30) and non-obese individuals (n = 14; 18.5 mood conditions). Following 3-h of food deprivation, all participants completed a mood induction, and then were exposed to their preferred high-calorie food items. HF HRV was assessed throughout. Obese and non-obese individuals were not significantly different in HF HRV during positive or negative mood induction. Obese individuals showed significantly greater levels of HF HRV during presentation of their preferred high-calorie food items than non-obese individuals, particularly in the positive mood condition. This is the first study to demonstrate increased vagal activity in response to food cues in obese individuals compared with non-obese individuals. Our findings warrant further investigation on the potential role o