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Sample records for vagal neurons cvns

  1. Chronic intermittent hypoxia-hypercapnia blunts heart rate responses and alters neurotransmission to cardiac vagal neurons.

    PubMed

    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.

  2. Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

    PubMed

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2016-12-17

    Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  4. Serotonin and cholecystokinin synergistically stimulate rat vagal primary afferent neurones

    PubMed Central

    Li, Y; Wu, X Y; Owyang, C

    2004-01-01

    Recent studies indicate that cholecystokinin (CCK) and serotonin (5-hydroxytryptamine, 5-HT) act via vagal afferent fibres to mediate gastrointestinal functions. In the present study, we characterized the interaction between CCK and 5-HT in the vagal primary afferent neurones. Single neuronal discharges of vagal primary afferent neurones innervating the duodenum were recorded from rat nodose ganglia. Two groups of nodose ganglia neurones were identified: group A neurones responded to intra-arterial injection of low doses of cholecystokinin octapeptide (CCK-8; 10–60 pmol); group B neurones responded only to high doses of CCK-8 (120–240 pmol), and were also activated by duodenal distention. CCK-JMV-180, which acts as an agonist in high-affinity states and as an antagonist in low-affinity states, dose dependently stimulated group A neurones, but inhibited the effect of the high doses of CCK-8 on group B neurones. Duodenal perfusion of 5-HT evoked dose-dependent increases in nodose neuronal discharges. Some neurones that responded to 5-HT showed no response to either high or low doses of CCK-8. A separate group of nodose neurones that possessed high-affinity CCK type A (CCK-A) receptors also responded to luminal infusion of 5-HT. Further, a subthreshold dose of CCK-8 (i.e. 5 pmol) produced no measurable electrophysiological effects but it augmented the neuronal responses to 5-HT. This potentiation effect of CCK-8 was eliminated by CR 1409. From these results we concluded that the vagal nodose ganglion contains neurones that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurones that express high-affinity CCK-A receptors also express 5-HT3 receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK. PMID:15235095

  5. Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus

    PubMed Central

    Izumi, Noriaki; Matsuyama, Hayato; Ko, Mifa; Shimizu, Yasutake; Takewaki, Tadashi

    2003-01-01

    Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 μs, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones. PMID:12813149

  6. Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

    PubMed Central

    Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

    2012-01-01

    Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

  7. Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis

    PubMed Central

    McAllen, Robin M; Salo, Lauren M; Paton, Julian F R; Pickering, Anthony E

    2011-01-01

    Abstract Cardiac vagal tone is an important indicator of cardiovascular health, and its loss is an independent risk factor for arrhythmias and mortality. Several studies suggest that this loss of vagal tone can occur at the cardiac ganglion but the factors affecting ganglionic transmissionin vivoare poorly understood. We have employed a novel approach allowing intracellular recordings from functionally connected cardiac vagal ganglion cells in the working heart–brainstem preparation. The atria were stabilisedin situpreserving their central neural connections, and ganglion cells (n = 32) were impaled with sharp microelectrodes. Cardiac ganglion cells with vagal synaptic inputs (spontaneous, n = 10; or electrically evoked from the vagus, n = 3) were identified as principal neurones and showed tonic firing responses to current injected to their somata. Cells lacking vagal inputs (n = 19, presumed interneurones) were quiescent but showed phasic firing responses to depolarising current. In principal cells the ongoing action potentials and EPSPs exhibited respiratory modulation, with peak frequency in post-inspiration. Action potentials arose from unitary EPSPs and autocorrelation of those events showed that each ganglion cell received inputs from a single active preganglionic source. Peripheral chemoreceptor, arterial baroreceptor and diving response activation all evoked high frequency synaptic barrages in these cells, always from the same single preganglionic source. EPSP amplitudes showed frequency dependent depression, leading to more spike failures at shorter inter-event intervals. These findings indicate that rather than integrating convergent inputs, cardiac vagal postganglionic neurones gate preganglionic inputs, so regulating the proportion of central parasympathetic tone that is transmitted on to the heart. PMID:22005679

  8. Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure.

    PubMed

    Ichige, Marcelo H A; Santos, Carla R; Jordão, Camila P; Ceroni, Alexandre; Negrão, Carlos E; Michelini, Lisete C

    2016-11-01

    Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by exaggerated sympathoexcitation and reduced parasympathetic activity. With 6 weeks of exercise training, HF-related loss of choline acetyltransferase (ChAT)-positive vagal preganglionic neurones is avoided, restoring the parasympathetic tonus to the heart, and the immunoreactivity of dopamine β-hydroxylase-positive premotor neurones that drive sympathetic outflow to the heart is reduced. Training-induced correction of autonomic dysfunction occurs even with the persistence of abnormal ventricular function. Strong positive correlation between improved parasympathetic tonus to the heart and increased ChAT immunoreactivity in vagal preganglionic neurones after training indicates this is a crucial mechanism to restore autonomic function in heart failure. Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative

  9. The central nucleus of the amygdala modulates gut-related neurons in the dorsal vagal complex in rats

    PubMed Central

    Zhang, Xueguo; Cui, Jinjuan; Tan, Zhenjun; Jiang, Chunhui; Fogel, Ronald

    2003-01-01

    Using retrograde tract-tracing and electrophysiological methods, we characterized the anatomical and functional relationship between the central nucleus of the amygdala and the dorsal vagal complex. Retrograde tract-tracing techniques revealed that the central nucleus of the amygdala projects to the dorsal vagal complex with a topographic distribution. Following injection of retrograde tracer into the vagal complex, retrogradely labelled neurons in the central nucleus of the amygdala were clustered in the central portion at the rostral level and in the medial part at the middle level of the nucleus. Few labelled neurons were seen at the caudal level. Electrical stimulation of the central nucleus of the amygdala altered the basal firing rates of 65 % of gut-related neurons in the nucleus of the solitary tract and in the dorsal motor nucleus of the vagus. Eighty-one percent of the neurons in the nucleus of the solitary tract and 47 % of the neurons in the dorsal motor nucleus were inhibited. Electrical stimulation of the central nucleus of the amygdala also modulated the response of neurons in the dorsal vagal complex to gastrointestinal stimuli. The predominant effect on the neurons of the nucleus of the solitary tract was inhibition. These results suggest that the central nucleus of the amygdala influences gut-related neurons in the dorsal vagal complex and provides a neuronal circuitry that explains the regulation of gastrointestinal activity by the amygdala. PMID:14555729

  10. Expression of Sex Steroid Hormone Receptors in Vagal Motor Neurons Innervating the Trachea and Esophagus in Mouse

    PubMed Central

    Mukudai, Shigeyuki; Ichi Matsuda, Ken; Bando, Hideki; Takanami, Keiko; Nishio, Takeshi; Sugiyama, Yoichiro; Hisa, Yasuo; Kawata, Mitsuhiro

    2016-01-01

    The medullary vagal motor nuclei, the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV), innervate the respiratory and gastrointestinal tracts. We conducted immunohistochemical analysis of expression of the androgen receptor (AR) and estrogen receptor α (ERα), in relation to innervation of the trachea and esophagus via vagal motor nuclei in mice. AR and ERα were expressed in the rostral NA and in part of the DMV. Tracing experiments using cholera toxin B subunit demonstrated that neurons of vagal motor nuclei that innervate the trachea and esophagus express AR and ERα. There was no difference in expression of sex steroid hormone receptors between trachea- and esophagus-innervating neurons. These results suggest that sex steroid hormones may act on vagal motor nuclei via their receptors, thereby regulating functions of the trachea and esophagus. PMID:27006520

  11. Evidence that antidromically stimulated vagal afferents activate inhibitory neurones innervating guinea-pig trachealis.

    PubMed Central

    Canning, B J; Undem, B J

    1994-01-01

    -selective agonist, acetyl-[Arg6, Sar9, Met (O2)11]-SP(6-11), elicited oesophagus-dependent relaxations of the trachealis that were abolished by oesophagus removal. Furthermore, pretreatment with the NK1-selective antagonists, CP 96345 and CP 99994, or pretreatment with a concentration of SR 48968 that also blocks NK3 receptors, markedly attenuated relaxations elicited by stimulation of the capsaicin-sensitive vagal pathways. 6. The data are consistent with the hypothesis that relaxations elicited by stimulation of capsaicin-sensitive vagal afferents involve tachykinin-mediated activation of peripheral NANC inhibitory neurones that are in some way associated with the oesophagus. The data also indicate that airway smooth muscle tone might be regulated by peripheral reflexes initiated by activation of capsaicin-sensitive afferent fibres. PMID:7869272

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25591867

  14. Vagal innervation of the aldosterone-sensitive HSD2 neurons in the NTS

    PubMed Central

    Shin, Jung-Won; Geerling, Joel C.; Loewy, Arthur D.

    2009-01-01

    The nucleus of the solitary tract (NTS) contains a unique subpopulation of aldosterone-sensitive neurons. These neurons express the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2) and are activated by sodium deprivation. They are located in the caudal NTS, a region which is densely innervated by the vagus nerve, suggesting that they could receive direct viscerosensory input from the periphery. To test this possibility, we injected the highly sensitive axonal tracer biotinylated dextran amine (BDA) into the left nodose ganglion in rats. Using confocal microscopy, we observed a sparse input from the vagus to most HSD2 neurons. Roughly 80% of the ipsilateral HSD2 neurons exhibited at least one close contact with a BDA-labeled vagal bouton, although most of these cells received only a few total contacts. Most of these contacts were axo-dendritic (~80%), while ~20% were axo-somatic. In contrast, the synaptic vesicular transporters VGLUT2 or GAD7 labeled much larger populations of boutons contacting HSD2-labeled dendrites and somata, suggesting that direct input from the vagus may only account for a minority of the information integrated by these neurons. In summary, the aldosterone-sensitive HSD2 neurons in the NTS appear to receive a small amount of direct viscerosensory input from the vagus nerve. The peripheral sites of origin and functional significance of this projection remain unknown. Combined with previously-identified central sources of input to these cells, the present finding indicates that the HSD2 neurons integrate humoral information with input from a variety of neural afferents. PMID:19010311

  15. Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism-associated MET receptor tyrosine kinase.

    PubMed

    Kamitakahara, Anna; Wu, Hsiao-Huei; Levitt, Pat

    2017-12-15

    Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a MET EGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD. © 2017 Wiley Periodicals, Inc.

  16. Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs.

    PubMed

    Lundberg, J M; Brodin, E; Saria, A

    1983-11-01

    The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves

  17. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

    PubMed Central

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

    2016-01-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

  18. Glutamatergic drive facilitates synaptic inhibition of dorsal vagal motor neurons after experimentally induced diabetes in mice

    PubMed Central

    Boychuk, Carie R.

    2016-01-01

    The role of central regulatory circuits in modulating diabetes-associated glucose dysregulation has only recently been under rigorous investigation. One brain region of interest is the dorsal motor nucleus of the vagus (DMV), which contains preganglionic parasympathetic motor neurons that regulate subdiaphragmatic visceral function. Previous research has demonstrated that glutamatergic and GABAergic neurotransmission are independently remodeled after chronic hyperglycemia/hypoinsulinemia. However, glutamatergic circuitry within the dorsal brain stem impinges on GABAergic regulation of the DMV. The present study investigated the role of glutamatergic neurotransmission in synaptic GABAergic control of DMV neurons after streptozotocin (STZ)-induced hyperglycemia/hypoinsulinemia by using electrophysiological recordings in vitro. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was elevated in DMV neurons from STZ-treated mice. The effect was abolished in the presence of the ionotropic glutamate receptor blocker kynurenic acid or the sodium channel blocker tetrodotoxin, suggesting that after STZ-induced hyperglycemia/hypoinsulinemia, increased glutamatergic receptor activity occurs at a soma-dendritic location on local GABA neurons projecting to the DMV. Although sIPSCs in DMV neurons normally demonstrated considerable amplitude variability, this variability was significantly increased after STZ-induced hyperglycemia/hypoinsulinemia. The elevated amplitude variability was not related to changes in quantal release, but rather correlated with significantly elevated frequency of sIPSCs in these mice. Taken together, these findings suggest that GABAergic regulation of central vagal circuitry responsible for the regulation of energy homeostasis undergoes complex functional reorganization after several days of hyperglycemia/hypoinsulinemia, including both glutamate-dependent and -independent forms of plasticity. PMID:27385796

  19. Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity.

    PubMed

    Iwasaki, Yusaku; Maejima, Yuko; Suyama, Shigetomo; Yoshida, Masashi; Arai, Takeshi; Katsurada, Kenichi; Kumari, Parmila; Nakabayashi, Hajime; Kakei, Masafumi; Yada, Toshihiko

    2015-03-01

    Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity. Copyright © 2015 the American Physiological Society.

  20. Coexistence of calbindin D-28k and NADPH-diaphorase in vagal and glossopharyngeal sensory neurons of the rat.

    PubMed

    Ichikawa, H; Helke, C J

    1996-10-07

    The presence and coexistence of calbindin D-28k-immunoreactivity (ir) and nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase activity (a marker of neurons that are presumed to convert L-arginine to L-citrulline and nitric oxide) were examined in the glossopharyngeal and vagal sensory ganglia (jugular, petrosal and nodose ganglia) of the rat. Calbindin D-28k-ir nerve cells were found in moderate and large numbers in the petrosal and nodose ganglia, respectively. Some calbindin D-28k-ir nerve cells were also observed in the jugular ganglion. NADPH-diaphorase positive nerve cells were localized to the jugular and nodose ganglia and were rare in the petrosal ganglion. A considerable portion (33-51%) of the NADPH-diaphorase positive neurons in these ganglia colocalized calbindin D-28k-ir. The presence and colocalization of calbindin D-28k-ir and NADPH-diaphorase activity in neurotransmitter-identified subpopulations of visceral sensory neurons were also studied. In all three ganglia, calcitonin gene-related peptide (CGRP)-ir was present in many NADPH-diaphorase positive neurons, a subset of which also contained calbindin D-28k-ir. In the nodose ganglion, many (42%) of tyrosine hydroxylase (TH)-ir neurons also contained NADPH diaphorase activity but did not contain calbindin D-28k-ir. These data are consistent with a potential co-operative role for calbindin D-28k and NADPH-diaphorase in the functions of a subpopulation of vagal and glossopharyngeal sensory neurons.

  1. IN VITRO RESEARCH OF THE ALTERATION OF NEURONS IN VAGAL CORE IN MEDULLA OBLONGATA AT ASPHYXIC DEATHS

    PubMed Central

    Haliti, Naim; Islami, Hilmi; Elezi, Nevzat; Shabani, Ragip; Abdullahu, Bedri; Dragusha, Gani

    2010-01-01

    The aim of this study was to research the morphological changes of neurons in the vagus nerve nuclei in medulla oblongata in asphyxia related death cases. Morphological changes that were investigated were mainly in the dorsal motor respiratory center (DMRC), nucleus tractus solitarius (nTS) and nucleus ambigus (nA) in the medulla oblongata. In our research, the autopsy material from asphyxia related death cases was used from various etiologies: monoxide carbon (CO), liquid drowning, strangulation, electricity, clinical-pathological death, firing weapon, explosive weapon, sharp and blunt objects and death cases due to accident. The material selected for research was taken from medulla oblongata and lungs from all lobes. The material from the medulla oblongata and lungs was fixed in a 10% solution of buffered formalin. Special histochemical methods for central nervous system (CNS) were employed like: Cresyl echt violet, toluidin blue, Sevier-Munger modification and Grimelius. For stereometrical analysis of the quantitative density of the neurons the universal testing system Weibel M42 was used. The acquired results show that in sudden asphyxia related death cases, there are alterations in the nuclei of vagal nerve in form of: central chromatolysis, axonal retraction, axonal fragmentation, intranuclear vacuolization, cytoplasmic vacuolization, edema, condensation and dispersion of substance of Nissl, proliferation of oligodendrocytes, astrocytes and microglia. The altered population of vagus nerve neurons does not show an important statistica! significarne compared to the overall quantity of the neurons in the nuclei of the vagus nerve (p<0,05). PMID:20846134

  2. Activation of anorexigenic pro-opiomelanocortin neurones during refeeding is independent of vagal and brainstem inputs.

    PubMed

    Fekete, C; Zséli, G; Singru, P S; Kádár, A; Wittmann, G; Füzesi, T; El-Bermani, W; Lechan, R M

    2012-11-01

    After fasting, satiety is observed within 2 h after reintroducing food, accompanied by activation of anorexigenic, pro-opiomelanocortin (POMC)-synthesising neurones in the arcuate nucleus (ARC), indicative of the critical role that α-melanocyte-stimulating hormone has in the regulation of meal size during refeeding. To determine whether refeeding-induced activation of POMC neurones in the arcuate is dependent upon the vagus nerve and/or ascending brainstem pathways, bilateral subdiaphragmatic vagotomy or transection of the afferent brainstem input to one side of the ARC was performed. One day after vagotomy or 2 weeks after brain surgery, animals were fasted and then refed for 2 h. Sections containing the ARC from vagotomised animals or animals with effective transection were immunostained for c-Fos and POMC to detect refeeding-induced activation of POMC neurones. Quantitative analyses of double-labelled preparations demonstrated that sham-operated and vagotomised animals markedly increased the number of c-Fos-immunoreactive (-IR) POMC neurones with refeeding. Furthermore, transection of the ascending brainstem pathway had no effect on diminishing c-Fos-immunoreactivity in POMC neurones on either side of the ARC, although it did diminish activation in a separate, subpopulation of neurones in the dorsomedial posterior ARC (dmpARC) on the transected side. We conclude that inputs mediated via the vagus nerve and/or arising from the brainstem do not have a primary role in refeeding-induced activation of POMC neurones in the ARC, and propose that these neurones may be activated solely by direct effects of circulating hormones/metabolites during refeeding. Activation of the dmpARC by refeeding indicates a previously unrecognised role for these neurones in appetite regulation in the rat. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

  3. Reduced mechanosensitivity of duodenal vagal afferent neurons after an acute switch from milk-based to plant-based diets in anaesthetized pigs.

    PubMed

    Bligny, D; Blat, S; Chauvin, A; Guérin, S; Malbert, C-H

    2005-06-01

    Acute changes in diet composition and/or origin alter gastric emptying and gastrointestinal motility. One of the hypotheses explaining these alterations involves changes in the sensitivity of duodenal vagal sensory neurons. The aim of this study was to evaluate the characteristics of multimodal duodenal vagal sensory neurons in 20 pigs feed either with milk-based or plant-based diets of identical caloric content. Twenty duodenal vagal afferents were recorded in anesthetized animal from the cervical vagus using the single fiber method. 10 pigs were fed with a milk-based diet (MD) for one month while the diet of the 10 other pigs was changed for plant-based diet (PD) the day preceding the recording session. The behavior of the receptors was tested in basal resting conditions and after challenges with duodenal intralipid and close intra-arterial injection of CCK, 5-HT or capsaicin with and without isovolumetric duodenal distensions at 20, 40 and 60 mmHg. All receptors were slowly adapting C type fiber with a receptor field located 6-7 cm distal to the pylorus. The rate of discharge during distension (20, 40 and 60 mmHg) combined with duodenal intralipid was significantly larger for MD compared with PD. Similarly, the rate of discharge observed during distensions performed with CCK and with 5-HT were greater for MD compared with PD while CCK and 5-HT without distension were equally stimulating for MD and PD. No significant difference was found between groups during capsaicin infusion irrespective of the stimulating pressure. In conclusion, a switch to plant-based diet, when compared to a milk-based diet, results in an overall decrease in mechanical sensitivity of duodenal neurons during lipid, 5HT and CCK challenges, but not in basal conditions or after capsaicin. This reduced sensitivity to distension may explain the diet-induced alteration of gastric emptying that is controlled primarily through a vago-vagal reflex.

  4. Mitochondrial modulation-induced activation of vagal sensory neuronal subsets by antimycin A, but not CCCP or rotenone, correlates with mitochondrial superoxide production.

    PubMed

    Stanford, Katherine R; Taylor-Clark, Thomas E

    2018-01-01

    Inflammation causes nociceptive sensory neuron activation, evoking debilitating symptoms and reflexes. Inflammatory signaling pathways are capable of modulating mitochondrial function, resulting in reactive oxygen species (ROS) production, mitochondrial depolarization and calcium release. Previously we showed that mitochondrial modulation with antimycin A, a complex III inhibitor, selectively stimulated nociceptive bronchopulmonary C-fibers via the activation of transient receptor potential (TRP) ankyrin 1 (A1) and vanilloid 1 (V1) cation channels. TRPA1 is ROS-sensitive, but there is little evidence that TRPV1 is activated by ROS. Here, we used dual imaging of dissociated vagal neurons to investigate the correlation of mitochondrial superoxide production (mitoSOX) or mitochondrial depolarization (JC-1) with cytosolic calcium (Fura-2AM), following mitochondrial modulation by antimycin A, rotenone (complex I inhibitor) and carbonyl cyanide m-chlorophenyl hydrazone (CCCP, mitochondrial uncoupling agent). Mitochondrial modulation by all agents selectively increased cytosolic calcium in a subset of TRPA1/TRPV1-expressing (A1/V1+) neurons. There was a significant correlation between antimycin A-induced calcium responses and mitochondrial superoxide in wild-type 'responding' A1/V1+ neurons, which was eliminated in TRPA1-/- neurons, but not TRPV1-/- neurons. Nevertheless, antimycin A-induced superoxide production did not always increase calcium in A1/V1+ neurons, suggesting a critical role of an unknown factor. CCCP caused both superoxide production and mitochondrial depolarization but neither correlated with calcium fluxes in A1/V1+ neurons. Rotenone-induced calcium responses in 'responding' A1/V1+ neurons correlated with mitochondrial depolarization but not superoxide production. Our data are consistent with the hypothesis that mitochondrial dysfunction causes calcium fluxes in a subset of A1/V1+ neurons via ROS-dependent and ROS-independent mechanisms.

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

    PubMed

    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.

  6. Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca(2+) Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.

    PubMed

    Iwasaki, Yusaku; Shimomura, Kenju; Kohno, Daisuke; Dezaki, Katsuya; Ayush, Enkh-Amar; Nakabayashi, Hajime; Kubota, Naoto; Kadowaki, Takashi; Kakei, Masafumi; Nakata, Masanori; Yada, Toshihiko

    2013-01-01

    Some of insulin's functions, including glucose/lipid metabolism, satiety and neuroprotection, involve the alteration of brain activities. Insulin could signal to the brain via penetrating through the blood-brain barrier and acting on the vagal afferents, while the latter remains unproved. This study aimed to clarify whether insulin directly regulates the nodose ganglion neurons (NGNs) of vagal afferents in mice. NGs expressed insulin receptor (IR) and insulin receptor substrate-2 (IRS2) mRNA, and some of NGNs were immunoreactive to IR. In patch-clamp and fura-2 microfluorometric studies, insulin (10(-12)∼10(-6) M) depolarized and increased cytosolic Ca(2+) concentration ([Ca(2+)]i) in single NGNs. The insulin-induced [Ca(2+)]i increases were attenuated by L- and N-type Ca(2+) channel blockers, by phosphatidylinositol 3 kinase (PI3K) inhibitor, and in NGNs from IRS2 knockout mice. Half of the insulin-responsive NGNs contained cocaine- and amphetamine-regulated transcript. Neuronal fibers expressing IRs were distributed in/around pancreatic islets. The NGNs innervating the pancreas, identified by injecting retrograde tracer into the pancreas, responded to insulin with much greater incidence than unlabeled NGNs. Insulin concentrations measured in pancreatic vein was 64-fold higher than that in circulation. Elevation of insulin to 10(-7) M recruited a remarkably greater population of NGNs to [Ca(2+)]i increases. Systemic injection of glibenclamide rapidly released insulin and phosphorylated AKT in NGs. Furthermore, in IRS2 knockout mice, insulin action to suppress [Ca(2+)]i in orexigenic ghrelin-responsive neurons in hypothalamic arcuate nucleus was intact while insulin action on NGN was markedly attenuated, suggesting a possible link between impaired insulin sensing by NGNs and hyperphagic obese phenotype in IRS2 knockout mice These data demonstrate that insulin directly activates NGNs via IR-IRS2-PI3K-AKT-cascade and depolarization-gated Ca(2+) influx. Pancreas

  7. The role of central 5-HT1A receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats

    PubMed Central

    Wang, Yun; Ramage, Andrew G

    2001-01-01

    Experiments were performed to determine whether 5-HT1A receptors (a) modulate the activity of cardiac and bronchoconstrictor vagal preganglionic neurones (CVPNs and BVPNs) in the nucleus ambiguus (NA) and (b) are involved in pulmonary C-fibre afferent-evoked excitation of CVPNs, by right-atrial injections of phenylbiguanide (PBG). These experiments were carried out on α-chloralose-anaesthetized, artificially ventilated and atenolol (1 mg kg−1)-pretreated cats. The ionophoretic application of 8-OH-DPAT (a selective 5-HT1A receptor agonist) influenced the activity of 16 of the 19 CVPNs tested. 8-OH-DPAT tended to cause inhibition at low currents (40 nA) and excitation at high currents (120 nA). The activity of 15 of these neurones increased in response to the application of 8-OH-DPAT. In six of the CVPNs tested, this excitatory action of 8-OH-DPAT was attenuated by co-application of the selective 5-HT1A receptor antagonist WAY-100635. The pulmonary C-fibre afferent-evoked excitation of eight CVPNs was attenuated by ionophoretic application of WAY-100635. In three out of four CVPNs, the ionophoretic application of PBG caused excitation. In five out of the nine identified BVPNs that were tested with ionophoretic application of 8-OH-DPAT, excitation was observed that was attenuated by WAY-100635. WAY-100635 (i.v. or intra-cisternally) also reversed bradycardia, hypotension and the decrease in phrenic nerve activity evoked by the i.v. application of 8-OH-DPAT (42 μg kg−1). In conclusion, the data indicate that 5-HT1A receptors located in the NA play an important role in the reflex activation of CVPNs and BVPNs, and support the view that overall, these receptors play a fundamental role in the reflex regulation of parasympathetic outflow. PMID:11691870

  8. Comparison of the spatial distribution of endopeptidase-24.11 with substance P, substance P receptor (NK-1r) and gastric efferent neurons in the dorsal vagal complex of the rat.

    PubMed

    Ladic, L; Buchan, A

    1997-01-24

    The spatial location of neutral endopeptidase 24.11 (NEP) immunoreactivity was compared to that of substance P (SP), SP receptor (NK-1r) and identified gastric efferent neurons in the dorsal vagal complex in rat brainstem. The majority of NEP labeling was observed caudal to the obex. Neutral endopeptidase-immunoreactivity was associated with the central canal, ependyma and blood vessels, and surrounded the area postrema. A comparison of the results of immunocytochemical and retrograde tracing experiments demonstrated the absence of co-labeling of neurons or their process with NEP and either substance P or NK-1r. Furthermore, no NEP-immunoreactivity was observed in the vicinity of identified gastric efferents in the dorsal motor nucleus of the vagus. These results would suggest that NEP does not degrade SP in the vicinity of gastric efferent neurons.

  9. Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

    PubMed Central

    Kember, Guy; Ardell, Jeffrey L.; Armour, John A.; Zamir, Mair

    2014-01-01

    Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity. PMID:25479368

  10. Vagal nerve stimulation therapy: what is being stimulated?

    PubMed

    Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

    2014-01-01

    Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

  11. Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons

    PubMed Central

    Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David

    2014-01-01

    Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676

  12. Modulation of gastrointestinal vagal neurocircuits by hyperglycemia

    PubMed Central

    Browning, Kirsteen N.

    2013-01-01

    Glucose sensing within autonomic neurocircuits is critical for the effective integration and regulation of a variety of physiological homeostatic functions including the co-ordination of vagally-mediated reflexes regulating gastrointestinal (GI) functions. Glucose regulates GI functions via actions at multiple sites of action, from modulating the activity of enteric neurons, endocrine cells, and glucose transporters within the intestine, to regulating the activity and responsiveness of the peripheral terminals, cell bodies and central terminals of vagal sensory neurons, to modifying both the activity and synaptic responsiveness of central brainstem neurons. Unsurprisingly, significant impairment in GI functions occurs in pathophysiological states where glucose levels are dysregulated, such as diabetes. A substantial obstacle to the development of new therapies to modify the disease, rather than treat the symptoms, are the gaps in our understanding of the mechanisms by which glucose modulates GI functions, particularly vagally-mediated responses and a more complete understanding of disease-related plasticity within these neurocircuits may open new avenues and targets for research. PMID:24324393

  13. Caudal fourth ventricular administration of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside regulates glucose and counterregulatory hormone profiles, dorsal vagal complex metabolosensory neuron function, and hypothalamic Fos expression.

    PubMed

    Ibrahim, Baher A; Tamrakar, Pratistha; Gujar, Amit D; Cherian, Ajeesh Koshy; Briski, Karen P

    2013-09-01

    This study investigated the hypothesis that estrogen controls hindbrain AMP-activated protein kinase (AMPK) activity and regulation of blood glucose, counterregulatory hormone secretion, and hypothalamic nerve cell transcriptional status. Dorsal vagal complex A2 noradrenergic neurons were laser microdissected from estradiol benzoate (E)- or oil (O)-implanted ovariectomized female rats after caudal fourth ventricular (CV4) delivery of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR), for Western blot analysis. E advanced AICAR-induced increases in A2 phospho-AMPK (pAMPK) expression and in blood glucose levels and was required for augmentation of Fos, estrogen receptor-α (ERα), monocarboxylate transporter-2, and glucose transporter-3 protein in A2 neurons and enhancement of corticosterone secretion by this treatment paradigm. CV4 AICAR also resulted in site-specific modifications in Fos immunolabeling of hypothalamic metabolic structures, including the paraventricular, ventromedial, and arcuate nuclei. The current studies demonstrate that estrogen regulates AMPK activation in caudal hindbrain A2 noradrenergic neurons during pharmacological replication of energy shortage in this area of the brain, and that this sensor is involved in neural regulation of glucostasis, in part, through control of corticosterone secretion. The data provide unique evidence that A2 neurons express both ERα and -β proteins and that AMPK upregulates cellular sensitivity to ERα-mediated signaling during simulated energy insufficiency. The results also imply that estrogen promotes glucose and lactate uptake by these cells under those conditions. Evidence for correlation between hindbrain AMPK and hypothalamic nerve cell genomic activation provides novel proof for functional connectivity between this hindbrain sensor and higher order metabolic brain loci while demonstrating a modulatory role for estrogen in this interaction. Copyright © 2013 Wiley Periodicals, Inc.

  14. Vagal Afferent Innervation of the Airways in Health and Disease

    PubMed Central

    Mazzone, Stuart B.

    2016-01-01

    Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions. PMID:27279650

  15. Caudal hindbrain lactate infusion alters glucokinase, SUR1, and neuronal substrate fuel transporter gene expression in the dorsal vagal complex, lateral hypothalamic area, and ventromedial nucleus hypothalamus of hypoglycemic male rats.

    PubMed

    Vavaiya, Kamlesh V; Briski, Karen P

    2007-10-24

    While in vitro studies show that the oxidizable energy substrate, lactate, is a preferred fuel for CNS neurons during states of energy crisis, and that lactate may regulate neuronal glucose uptake under those conditions, its role in neuronal function in vivo remains controversial. Glucose-excited neurons in hindbrain dorsal vagal complex (DVC) monitor both glucose and lactate, and express both the glucose sensor, glucokinase (GK), and the SUR1 subunit of the plasma membrane energy transducer, K(ATP). Fourth ventricular lactate infusion exacerbates insulin-induced hypoglycemia (IIH) and IIH-associated patterns of DVC neuronal activation. We investigated the hypothesis that during glucoprivation, lactate regulates neuronal monocarboxylate and glucose transporter gene transcription in the DVC, and adjustments in these gene profiles are correlated with altered GK and SUR1 mRNA expression. We also examined whether caudal hindbrain lactate repletion alters the impact of hypoglycemia on substrate fuel uptake and metabolic sensing functions in other characterized metabolic monitoring sites, e.g., the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA). qPCR was used to measure MCT2, GLUT3, GLUT4, GK, and SUR1 transcripts in the microdissected DVC, VMH, and LHA from groups of male rats treated by continuous infusion of aCSF or lactate into the caudal fourth ventricle (CV4), initiated prior to injection of Humulin R or saline. Blood glucose was decreased in response to insulin, a response that was significantly augmented by CV4 lactate infusion. IIH alone did not alter mean DVC MCT2, GLUT3, GLUT4, GK, or SUR1 mRNA levels, but these transcripts were increased in the lactate plus insulin group, relative to both euglycemic and aCSF-infused hypoglycemic rats. IIH decreased MCT2, GLUT3, and SUR1 gene profiles in the VMH; CV4 lactate infusion during IIH further diminished these transcripts, and suppressed GLUT4 and GK mRNA levels in this site. In LHA, IIH

  16. Estrogen regulates energy metabolic pathway and upstream adenosine 5'-monophosphate-activated protein kinase and phosphatase enzyme expression in dorsal vagal complex metabolosensory neurons during glucostasis and hypoglycemia.

    PubMed

    Tamrakar, Pratistha; Ibrahim, Baher A; Gujar, Amit D; Briski, Karen P

    2015-02-01

    The ability of estrogen to shield the brain from the bioenergetic insult hypoglycemia is unclear. Estradiol (E) prevents hypoglycemic activation of the energy deficit sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) in hindbrain metabolosensory A2 noradrenergic neurons. This study investigates the hypothesis that estrogen regulates A2 AMPK through control of fuel metabolism and/or upstream protein kinase/phosphatase enzyme expression. A2 cells were harvested by laser microdissection after insulin or vehicle (V) injection of E- or oil (O)-implanted ovariectomized female rats. Cell lysates were evaluated by immunoblot for glycolytic, tricarboxylic acid cycle, respiratory chain, and acetyl-CoA-malonyl-CoA pathway enzymes. A2 phosphofructokinase (PFKL), isocitrate dehydrogenase, pyruvate dehydrogenase, and ATP synthase subunit profiles were elevated in E/V vs. O/V; hypoglycemia augmented PFKL and α-ketoglutarate dehydrogenase expression in E only. Hypoglycemia increased A2 Ca(2+) /calmodulin-dependent protein kinase-β in O and reduced protein phosphatase in both groups. A2 phospho-AMPK levels were equivalent in O/V vs. E/V but elevated during hypoglycemia in O only. These results implicate E in compensatory upregulation of substrate catabolism and corresponding maintenance of energy stability of A2 metabolosensory neurons during hypoglycemia, outcomes that support the potential viability of molecular substrates for hormone action as targets for therapies alleviating hypoglycemic brain injury. © 2014 Wiley Periodicals, Inc.

  17. Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology

    PubMed Central

    Browning, Kirsteen N.

    2015-01-01

    Vagal neurocircuits are vitally important in the co-ordination and modulation of GI reflexes and homeostatic functions. 5-hydroxytryptamine (5-HT; serotonin) is critically important in the regulation of several of these autonomic gastrointestinal (GI) functions including motility, secretion and visceral sensitivity. While several 5-HT receptors are involved in these physiological responses, the ligand-gated 5-HT3 receptor appears intimately involved in gut-brain signaling, particularly via the afferent (sensory) vagus nerve. 5-HT is released from enterochromaffin cells in response to mechanical or chemical stimulation of the GI tract which leads to activation of 5-HT3 receptors on the terminals of vagal afferents. 5-HT3 receptors are also present on the soma of vagal afferent neurons, including GI vagal afferent neurons, where they can be activated by circulating 5-HT. The central terminals of vagal afferents also exhibit 5-HT3 receptors that function to increase glutamatergic synaptic transmission to second order neurons of the nucleus tractus solitarius within the brainstem. While activation of central brainstem 5-HT3 receptors modulates visceral functions, it is still unclear whether central vagal neurons, i.e., nucleus of the tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) neurons themselves also display functional 5-HT3 receptors. Thus, activation of 5-HT3 receptors may modulate the excitability and activity of gastrointestinal vagal afferents at multiple sites and may be involved in several physiological and pathophysiological conditions, including distention- and chemical-evoked vagal reflexes, nausea, and vomiting, as well as visceral hypersensitivity. PMID:26578870

  18. Factors Regulating Vagal Sensory Development: Potential Role in Obesities of Developmental Origin

    PubMed Central

    Fox, Edward A.; Murphy, Michelle C.

    2008-01-01

    Contributors to increased obesity in children may include perinatal under- or overnutrition. Humans and rodents raised under these conditions develop obesity, which like obesities of other etiologies has been associated with increased meal size. Since vagal sensory innervation of the gastrointestinal (GI) tract transmits satiation signals that regulate meal size, one mechanism through which abnormal perinatal nutrition could increase meal size is by altering vagal development, possibly by causing changes in the expression of factors that control it. Therefore, we have begun to characterize development of vagal innervation of the GI tract and the expression patterns and functions of the genes involved in this process. Important events in development of mouse vagal GI innervation occurred between midgestation and the second postnatal week, suggesting they could be vulnerable to effects of abnormal nutrition preor postnatally. One gene investigated was brain- derived neurotrophic factor (BDNF), which regulates survival of a subpopulation of vagal sensory neurons. BDNF was expressed in some developing stomach wall tissues innervated by vagal afferents. At birth, mice deficient in BDNF exhibited a 50% reduction of putative intraganglionic laminar ending mechanoreceptor precursors, and a 50% increase in axons that had exited fiber bundles. Additionally, BDNF was required for patterning of individual axons and fiber bundles in the antrum and differentiation of intramuscular array mechanoreceptors in the forestomach. It will be important to determine whether abnormal perinatal environments alter development of vagal sensory innervation of the GI tract, involving effects on expression of BDNF, or other factors regulating vagal development. PMID:18234244

  19. Putative roles of neuropeptides in vagal afferent signaling

    PubMed Central

    de Lartigue, Guillaume

    2014-01-01

    The vagus nerve is a major pathway by which information is communicated between the brain and peripheral organs. Sensory neurons of the vagus are located in the nodose ganglia. These vagal afferent neurons innervate the heart, the lung and the gastrointestinal tract, and convey information about peripheral signals to the brain important in the control of cardiovascular tone, respiratory tone, and satiation, respectively. Glutamate is thought to be the primary neurotransmitter involved in conveying all of this information to the brain. It remains unclear how a single neurotransmitter can regulate such an extensive list of physiological functions from a wide range of visceral sites. Many neurotransmitters have been identified in vagal afferent neurons and have been suggested to modulate the physiological functions of glutamate. Specifically, the anorectic peptide transmitters, cocaine and amphetamine regulated transcript (CART) and the orexigenic peptide transmitters, melanin concentrating hormone (MCH) are differentially regulated in vagal afferent neurons and have opposing effects on food intake. Using these two peptides as a model, this review will discuss the potential role of peptide transmitters in providing a more precise and refined modulatory control of the broad physiological functions of glutamate, especially in relation to the control of feeding. PMID:24650553

  20. Gut vagal afferents differentially modulate innate anxiety and learned fear.

    PubMed

    Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

    2014-05-21

    Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

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

    PubMed

    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.

  2. Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish Cellular organization and neurotransmitters

    PubMed Central

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

    2009-01-01

    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 which 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 (±)-α-amino-3-hydroxy-5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediates 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. PMID:19598285

  3. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

    PubMed

    Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

    2014-07-01

    It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." © FASEB.

  4. VERSATILE, HIGH-RESOLUTION ANTEROGRADE LABELING OF VAGAL EFFERENT PROJECTIONS WITH DEXTRAN AMINES

    PubMed Central

    Walter, Gary C.; Phillips, Robert J.; Baronowsky, Elizabeth A.; Powley, Terry L.

    2009-01-01

    None of the anterograde tracers used to label and investigate vagal preganglionic neurons projecting to the viscera has proved optimal for routine and extensive labeling of autonomic terminal fields. To identify an alternative tracer protocol, the present experiment evaluated whether dextran conjugates, which have produced superior results in the CNS, might yield widespread and effective labeling of long, fine-caliber vagal efferents in the peripheral nervous system. The dextran conjugates that were evaluated proved reliable and versatile for labeling the motor neuron pool in its entirety, for single- and multiple-labeling protocols, for both conventional and confocal fluorescence microscopy, and for permanent labeling protocols for brightfield microscopy of the projections to the gastrointestinal (GI) tract. Using a standard ABC kit followed by visualization with DAB as the chromagen, Golgi-like labeling of the vagal efferent terminal fields in the GI wall was achieved with the biotinylated dextrans. The definition of individual terminal varicosities was so sharp and detailed that it was routinely practical to examine the relationship of putative vagal efferent contacts (by the criteria of high magnification light microscopy) with the dendritic and somatic architecture of counterstained neurons in the myenteric plexus. Overall, dextran conjugates provide high-definition labeling of an extensive vagal motor pool in the GI tract, and offer considerable versatility when multiple-staining protocols are needed to elucidate the complexities of the innervation of the gut. PMID:19056424

  5. Effect of mCOUP-TF1 deficiency on the glossopharyngeal and vagal sensory ganglia.

    PubMed

    Ichikawa, H; Lin, S-C; Tsai, S Y; Tsai, M-J; Sugimoto, T

    2004-07-16

    Immunohistochemistry for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase and calbindin D-28k was performed on the glossopharyngeal and vagal ganglia in mCOUP-TFI knockout mice to know the effect of its deficiency on different types of primary sensory neurons. In wild type and heterozygous mice, the glossopharyngeal and vagal ganglia contained abundant CGRP-, tyrosine hydroxylase- and calbindin D-28k-immunoreactive (IR) neurons. In the ganglia of mCOUP-TFI knockout mice, a 38% decrease of CGRP-IR neurons was detected. However, the number of tyrosine hydroxylase- or calbindin D-28k-neurons was not altered by the mCOUP-TFI deficiency. In the tongue of knockout mice, the number of CGRP-IR nerve fibers decreased compared to wild-type and heterozygous mice. The development of CGRP-IR petrosal neurons, which supply innervation of the tongue, may depend on mCOUP-TFI.

  6. Vagal Sensory Innervation of the Gastric Sling Muscle and Antral Wall: Implications for GERD?

    PubMed Central

    Powley, Terry L.; Gilbert, Jared M.; Baronowsky, Elizabeth A.; Billingsley, Cherie N.; Martin, Felecia N.; Phillips, Robert J.

    2012-01-01

    Background The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. Methods Sprague Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days post-injection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal were counterstained. Key Results The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with interstitial cells of Cajal. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings (IGLEs), the two types of mechanoreceptors found throughout stomach smooth muscle. Conclusions & Inferences The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors. PMID:22925069

  7. Validation and characterization of a novel method for selective vagal deafferentation of the gut.

    PubMed

    Diepenbroek, Charlene; Quinn, Danielle; Stephens, Ricky; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; de Lartigue, Guillaume

    2017-10-01

    There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate models. This method provides improved tissue specificity and superior separation of afferent and efferent signaling compared with vagotomy, capsaicin, and subdiaphragmatic deafferentation. NEW & NOTEWORTHY We develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons. This reliable approach provides superior tissue specificity and selectivity for vagal afferent over efferent targeting than traditional approaches. It can be used to address questions about the role of gut to brain signaling in physiological and pathophysiological conditions. Copyright © 2017 the American Physiological Society.

  8. Cardiac Vagal Regulation and Early Peer Status

    ERIC Educational Resources Information Center

    Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.

    2007-01-01

    A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

  9. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

    PubMed

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

  10. Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor activation

    PubMed Central

    Brailoiu, G Cristina; Benamar, Khalid; Arterburn, Jeffrey B; Gao, Erhe; Rabinowitz, Joseph E; Koch, Walter J; Brailoiu, Eugen

    2013-01-01

    In addition to acting on mineralocorticoid receptors, aldosterone has been recently shown to activate the G protein-coupled oestrogen receptor (GPER) in vascular cells. In light of the newly identified role for GPER in vagal cardiac control, we examined whether or not aldosterone activates GPER in rat nucleus ambiguus. Aldosterone produced a dose-dependent increase in cytosolic Ca2+ concentration in retrogradely labelled cardiac vagal neurons of nucleus ambiguus; the response was abolished by pretreatment with the GPER antagonist G-36, but was not affected by the mineralocorticoid receptor antagonists, spironolactone and eplerenone. In Ca2+-free saline, the response to aldosterone was insensitive to blockade of the Ca2+ release from lysosomes, while it was reduced by blocking the Ca2+ release via ryanodine receptors and abolished by blocking the IP3 receptors. Aldosterone induced Ca2+ influx via P/Q-type Ca2+ channels, but not via L-type and N-type Ca2+ channels. Aldosterone induced depolarization of cardiac vagal neurons of nucleus ambiguus that was sensitive to antagonism of GPER but not of mineralocorticoid receptor. in vivo studies, using telemetric measurement of heart rate, indicate that microinjection of aldosterone into the nucleus ambiguus produced a dose-dependent bradycardia in conscious, freely moving rats. Aldosterone-induced bradycardia was blocked by the GPER antagonist, but not by the mineralocorticoid receptor antagonists. In summary, we report for the first time that aldosterone decreases heart rate by activating GPER in cardiac vagal neurons of nucleus ambiguus. PMID:23878371

  11. Architecture of Vagal Motor Units Controlling Striated Muscle of Esophagus: Peripheral Elements Patterning Peristalsis?

    PubMed Central

    Powley, Terry L.; Mittal, Ravinder K.; Baronowsky, Elizabeth A.; Hudson, Cherie N.; Martin, Felecia N.; McAdams, Jennifer L.; Mason, Jacqueline K.; Phillips, Robert J.

    2013-01-01

    Little is known about the architecture of the vagal motor units that control esophageal striated muscle, in spite of the fact that these units are necessary, and responsible, for peristalsis. The present experiment was designed to characterize the motor neuron projection fields and terminal arbors forming esophageal motor units. Nucleus ambiguus compact formation neurons of the rat were labeled by bilateral intracranial injections of the anterograde tracer dextran biotin. After tracer transport, thoracic and abdominal esophagi were removed and prepared as whole mounts of muscle wall without mucosa or submucosa. Labeled terminal arbors of individual vagal motor neurons (n = 78) in the esophageal wall were inventoried, digitized and analyzed morphometrically. The size of individual vagal motor units innervating striated muscle, throughout thoracic and abdominal esophagus, averaged 52 endplates per motor neuron, a value indicative of fine motor control. A majority (77%) of the motor terminal arbors also issued one or more collateral branches that contacted neurons, including nitric oxide synthase-positive neurons, of local myenteric ganglia. Individual motor neuron terminal arbors co-innervated, or supplied endplates in tandem to, both longitudinal and circular muscle fibers in roughly similar proportions (i.e., two endplates to longitudinal for every three endplates to circular fibers). Both the observation that vagal motor unit collaterals project to myenteric ganglia and the fact that individual motor units co-innervate longitudinal and circular muscle layers are consistent with the hypothesis that elements contributing to peristaltic programming inhere, or are “hardwired,” in the peripheral architecture of esophageal motor units. PMID:24044976

  12. Architecture of vagal motor units controlling striated muscle of esophagus: peripheral elements patterning peristalsis?

    PubMed

    Powley, Terry L; Mittal, Ravinder K; Baronowsky, Elizabeth A; Hudson, Cherie N; Martin, Felecia N; McAdams, Jennifer L; Mason, Jacqueline K; Phillips, Robert J

    2013-12-01

    Little is known about the architecture of the vagal motor units that control esophageal striated muscle, in spite of the fact that these units are necessary, and responsible, for peristalsis. The present experiment was designed to characterize the motor neuron projection fields and terminal arbors forming esophageal motor units. Nucleus ambiguus compact formation neurons of the rat were labeled by bilateral intracranial injections of the anterograde tracer dextran biotin. After tracer transport, thoracic and abdominal esophagi were removed and prepared as whole mounts of muscle wall without mucosa or submucosa. Labeled terminal arbors of individual vagal motor neurons (n=78) in the esophageal wall were inventoried, digitized and analyzed morphometrically. The size of individual vagal motor units innervating striated muscle, throughout thoracic and abdominal esophagus, averaged 52 endplates per motor neuron, a value indicative of fine motor control. A majority (77%) of the motor terminal arbors also issued one or more collateral branches that contacted neurons, including nitric oxide synthase-positive neurons, of local myenteric ganglia. Individual motor neuron terminal arbors co-innervated, or supplied endplates in tandem to, both longitudinal and circular muscle fibers in roughly similar proportions (i.e., two endplates to longitudinal for every three endplates to circular fibers). Both the observation that vagal motor unit collaterals project to myenteric ganglia and the fact that individual motor units co-innervate longitudinal and circular muscle layers are consistent with the hypothesis that elements contributing to peristaltic programming inhere, or are "hardwired," in the peripheral architecture of esophageal motor units. © 2013.

  13. Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms.

    PubMed

    Egerod, Kristoffer L; Petersen, Natalia; Timshel, Pascal N; Rekling, Jens C; Wang, Yibing; Liu, Qinghua; Schwartz, Thue W; Gautron, Laurent

    2018-06-01

    G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Na v 1.8-expressing afferents. GPCRs for gut hormones that were the most enriched in Na v 1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Na v 1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Na v 1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  14. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways.

    PubMed

    Suarez, Andrea N; Hsu, Ted M; Liu, Clarissa M; Noble, Emily E; Cortella, Alyssa M; Nakamoto, Emily M; Hahn, Joel D; de Lartigue, Guillaume; Kanoski, Scott E

    2018-06-05

    The vagus nerve is the primary means of neural communication between the gastrointestinal (GI) tract and the brain. Vagally mediated GI signals activate the hippocampus (HPC), a brain region classically linked with memory function. However, the endogenous relevance of GI-derived vagal HPC communication is unknown. Here we utilize a saporin (SAP)-based lesioning procedure to reveal that selective GI vagal sensory/afferent ablation in rats impairs HPC-dependent episodic and spatial memory, effects associated with reduced HPC neurotrophic and neurogenesis markers. To determine the neural pathways connecting the gut to the HPC, we utilize monosynaptic and multisynaptic virus-based tracing methods to identify the medial septum as a relay connecting the medial nucleus tractus solitarius (where GI vagal afferents synapse) to dorsal HPC glutamatergic neurons. We conclude that endogenous GI-derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem-septal pathway, thereby identifying a previously unknown role for the gut-brain axis in memory control.

  15. Increased Vagal Tone and Sleep Apnea Syndrome.

    PubMed

    Ahmed, Tosaddak

    2016-01-01

    It has been observed that atrial overdrive pacing abolishes sleep apnea syndrome, but how it does so has not been explained. There is a possibility that it sends a retrograde inhibitory impulse to the vagal center in the brainstem, which in turn reduces the vagal tone, and thus prevents sleep apnea. Therefore, medical vagolytics such as atropine type of drugs should have the same effect. This is a case report of such an attempt.

  16. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity

    PubMed Central

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin brainstem slices from rats that were exposed to either a control diet or HFD from pregnancy day 13. Our data demonstrate that following perinatal HFD: (i) DMV neurones had decreased excitability and input resistance with a reduced ability to fire action potentials; (ii) the proportion of DMV neurones excited by cholecystokinin (CCK) was unaltered but the proportion of neurones in which CCK increased excitatory glutamatergic synaptic inputs was reduced; (iii) the tonic activation of presynaptic group II metabotropic glutamate receptors on inhibitory nerve terminals was attenuated, allowing modulation of GABAergic synaptic transmission; and (iv) the size and dendritic arborization of gastric-projecting DMV neurones was increased. These results suggest that perinatal HFD exposure compromises the excitability and responsiveness of gastric-projecting DMV neurones, even in the absence of obesity, suggesting that attenuation of vago-vagal reflex signalling may precede the development of obesity. PMID:25556801

  17. Vagal sensory innervation of the gastric sling muscle and antral wall: implications for gastro-esophageal reflux disease?

    PubMed

    Powley, T L; Gilbert, J M; Baronowsky, E A; Billingsley, C N; Martin, F N; Phillips, R J

    2012-10-01

    The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. Sprague-Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days postinjection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal (ICC) were counterstained. The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with ICC. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings, the two types of mechanoreceptors found throughout stomach smooth muscle. The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors. © 2012 Blackwell Publishing Ltd.

  18. Police work stressors and cardiac vagal control.

    PubMed

    Andrew, Michael E; Violanti, John M; Gu, Ja K; Fekedulegn, Desta; Li, Shengqiao; Hartley, Tara A; Charles, Luenda E; Mnatsakanova, Anna; Miller, Diane B; Burchfiel, Cecil M

    2017-09-10

    This study examines relationships between the frequency and intensity of police work stressors and cardiac vagal control, estimated using the high frequency component of heart rate variability (HRV). This is a cross-sectional study of 360 officers from the Buffalo New York Police Department. Police stress was measured using the Spielberger police stress survey, which includes exposure indices created as the product of the self-evaluation of how stressful certain events were and the self-reported frequency with which they occurred. Vagal control was estimated using the high frequency component of resting HRV calculated in units of milliseconds squared and reported in natural log scale. Associations between police work stressors and vagal control were examined using linear regression for significance testing and analysis of covariance for descriptive purposes, stratified by gender, and adjusted for age and race/ethnicity. There were no significant associations between police work stressor exposure indices and vagal control among men. Among women, the inverse associations between the lack of support stressor exposure and vagal control were statistically significant in adjusted models for indices of exposure over the past year (lowest stressor quartile: M = 5.57, 95% CI 5.07 to 6.08, and highest stressor quartile: M = 5.02, 95% CI 4.54 to 5.51, test of association from continuous linear regression of vagal control on lack of support stressor β = -0.273, P = .04). This study supports an inverse association between lack of organizational support and vagal control among female but not male police officers. © 2017 Wiley Periodicals, Inc.

  19. Vagal Flexibility: A Physiological Predictor of Social Sensitivity

    PubMed Central

    Muhtadie, Luma; Akinola, Modupe; Koslov, Katrina; Mendes, Wendy Berry

    2015-01-01

    This research explores vagal flexibility— dynamic modulation of cardiac vagal control—as an individual-level physiological index of social sensitivity. In 4 studies, we test the hypothesis that individuals with greater cardiac vagal flexibility, operationalized as higher cardiac vagal tone at rest and greater cardiac vagal withdrawal (indexed by a decrease in respiratory sinus arrhythmia) during cognitive or attentional demand, perceive social-emotional information more accurately and show greater sensitivity to their social context. Study 1 sets the foundation for this investigation by establishing that vagal flexibility can be elicited consistently in the laboratory and reliably over time. Study 2 demonstrates that vagal flexibility has different associations with psychological characteristics than does vagal tone, and that these characteristics are primarily social in nature. Study 3 links individual differences in vagal flexibility with accurate detection of social and emotional cues depicted in still facial images. Study 4 demonstrates that individuals with greater vagal flexibility respond to dynamic social feedback in a more context-sensitive manner than do individuals with less vagal flexibility. Specifically, compared with their less flexible counterparts, individuals with greater vagal flexibility, when assigned to receive negative social feedback, report more shame, show more pronounced blood pressure responses, and display less sociable behavior, but when receiving positive social feedback display more sociable behavior. Taken together, these findings suggest that vagal flexibility is a useful individual difference physiological predictor of social sensitivity, which may have implications for clinical, developmental, and health psychologists. PMID:25545841

  20. Vagal nerve stimulator: Evolving trends

    PubMed Central

    Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran

    2013-01-01

    Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future. PMID:23633829

  1. Vagal afferent fibres determine the oxytocin-induced modulation of gastric tone

    PubMed Central

    Holmes, Gregory M; Browning, Kirsteen N; Babic, Tanja; Fortna, Samuel R; Coleman, F Holly; Travagli, R Alberto

    2013-01-01

    Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT-induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS–DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose-dependent manner. The OXT-induced gastric relaxation was enhanced following bethanechol and reduced by l-NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic-mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric-projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT-induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit. PMID:23587885

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

    PubMed

    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.

  3. Domestic Violence and Vagal Reactivity to Peer Provocation

    PubMed Central

    Katz, Lynn Fainsilber

    2007-01-01

    This paper examined whether individual differences in children’s vagal reactivity to peer provocation was related to domestic violence within the family. It also examined the question of whether conduct-problem children who show vagal augmentation to peer provocation come from families with high levels of domestic violence. During the peer provocation, children were expecting to interact with a difficult peer while vagal reactivity was assessed. Groups were divided into children who showed vagal augmentation and vagal suppression to the stressful peer interaction. Findings indicated that conduct-problem children who showed vagal augmentation to interpersonal challenge came from families with the highest levels of domestic violence. Vagal augmentation was also associated with a greater number of conduct-related problems for those children exposed to high levels of domestic violence. Discussion highlights the role of individual differences in physiological reactivity in understanding children’s behavior problems in relation to domestic violence. PMID:17118516

  4. Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.

    PubMed

    Peters, James H; Gallaher, Zachary R; Ryu, Vitaly; Czaja, Krzysztof

    2013-10-15

    Vagotomy, a severing of the peripheral axons of the vagus nerve, has been extensively utilized to determine the role of vagal afferents in viscerosensory signaling. Vagotomy is also an unavoidable component of some bariatric surgeries. Although it is known that peripheral axons of the vagus nerve degenerate and then regenerate to a limited extent following vagotomy, very little is known about the response of central vagal afferents in the dorsal vagal complex to this type of damage. We tested the hypothesis that vagotomy results in the transient withdrawal of central vagal afferent terminals from their primary central target, the nucleus of the solitary tract (NTS). Sprague-Dawley rats underwent bilateral subdiaphragmatic vagotomy and were sacrificed 10, 30, or 60 days later. Plastic changes in vagal afferent fibers and synapses were investigated at the morphological and functional levels by using a combination of an anterograde tracer, synapse-specific markers, and patch-clamp electrophysiology in horizontal brain sections. Morphological data revealed that numbers of vagal afferent fibers and synapses in the NTS were significantly reduced 10 days following vagotomy and were restored to control levels by 30 days and 60 days, respectively. Electrophysiology revealed transient decreases in spontaneous glutamate release, glutamate release probability, and the number of primary afferent inputs. Our results demonstrate that subdiaphragmatic vagotomy triggers transient withdrawal and remodeling of central vagal afferent terminals in the NTS. The observed vagotomy-induced plasticity within this key feeding center of the brain may be partially responsible for the response of bariatric patients following gastric bypass surgery. Copyright © 2013 Wiley Periodicals, Inc.

  5. Vagal tone during infant contingency learning and its disruption.

    PubMed

    Sullivan, Margaret Wolan

    2016-04-01

    This study used contingency learning to examine changes in infants' vagal tone during learning and its disruption. The heart rate of 160 five-month-old infants was recorded continuously during the first of two training sessions as they experienced an audiovisual event contingent on their pulling. Maternal reports of infant temperament were also collected. Baseline vagal tone, a measure of parasympathetic regulation of the heart, was related to vagal levels during the infants' contingency learning session, but not to their learner status. Vagal tone levels did not vary significantly over session minutes. Instead, vagal tone levels were a function of both individual differences in learner status and infant soothability. Vagal levels of infants who learned in the initial session were similar regardless of their soothability; however, vagal levels of infants who learned in a subsequent session differed as a function of soothability. Additionally, vagal levels during contingency disruption were significantly higher among infants in this group who were more soothable as opposed to those who were less soothable. The results suggest that contingency learning and disruption is associated with stable vagal tone in the majority of infants, but that individual differences in attention processes and state associated with vagal tone may be most readily observed during the disruption phase. © 2015 Wiley Periodicals, Inc.

  6. Vagal Tone During Infant Contingency Learning and Its Disruption

    PubMed Central

    Sullivan, Margaret Wolan

    2015-01-01

    This study used contingency learning to examine changes in infants’ vagal tone during learning and its disruption. The heart rate of 160 five-month-old infants was recorded continuously during the first of two training sessions as they experienced an audiovisual event contingent on their pulling. Maternal reports of infant temperament were also collected. Baseline vagal tone, a measure of parasympathetic regulation of the heart, was related to vagal levels during the infants’ contingency learning session, but not to their learner status. Vagal tone levels did not vary significantly over session minutes. Instead, vagal tone levels were a function of both individual differences in learner status and infant soothability. Vagal levels of infants who learned in the initial session were similar regardless of their soothability; however, vagal levels of infants who learned in a subsequent session differed as a function of soothability. Additionally, vagal levels during contingency disruption were significantly higher among infants in this group who were more soothable as opposed to those who were less soothable. The results suggest that contingency learning and disruption is associated with stable vagal tone in the majority of infants, but that individual differences in attention processes and state associated with vagal tone may be most readily observed during the disruption phase. PMID:26517573

  7. Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat

    PubMed Central

    Zhou, Shi-Yi; Lu, Yuan-Xu; Owyang, Chung

    2011-01-01

    Hyperglycemia has a profound effect on gastric motility. However, little is known about site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg dL−1 had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg dL−1), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10−5 M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT3 antagonist, 0.5 g kg−1) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, NG-nitro-L-arginine methyl ester (l-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia, and in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation. PMID:18356537

  8. The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia: Implications for neural control of cardiac excitability

    PubMed Central

    Herring, Neil; Cranley, James; Lokale, Michael N.; Li, Dan; Shanks, Julia; Alston, Eric N.; Girard, Beatrice M.; Carter, Emma; Parsons, Rodney L.; Habecker, Beth A.; Paterson, David J.

    2012-01-01

    The autonomic phenotype of congestive cardiac failure is characterised by high sympathetic drive and impaired vagal tone, which are independent predictors of mortality. We hypothesize that impaired bradycardia to peripheral vagal stimulation following high-level sympathetic drive is due to sympatho-vagal crosstalk by the adrenergic co-transmitters galanin and neuropeptide-Y (NPY). Moreover we hypothesize that galanin acts similarly to NPY by reducing vagal acetylcholine release via a receptor mediated, protein kinase-dependent pathway. Prolonged right stellate ganglion stimulation (10 Hz, 2 min, in the presence of 10 μM metoprolol) in an isolated guinea pig atrial preparation with dual autonomic innervation leads to a significant (p < 0.05) reduction in the magnitude of vagal bradycardia (5 Hz) maintained over the subsequent 20 min (n = 6). Immunohistochemistry demonstrated the presence of galanin in a small number of tyrosine hydroxylase positive neurons from freshly dissected stellate ganglion tissue sections. Following 3 days of tissue culture however, most stellate neurons expressed galanin. Stellate stimulation caused the release of low levels of galanin and significantly higher levels of NPY into the surrounding perfusate (n = 6, using ELISA). The reduction in vagal bradycardia post sympathetic stimulation was partially reversed by the galanin receptor antagonist M40 after 10 min (1 μM, n = 5), and completely reversed with the NPY Y2 receptor antagonist BIIE 0246 at all time points (1 μM, n = 6). Exogenous galanin (n = 6, 50–500 nM) also reduced the heart rate response to vagal stimulation but had no effect on the response to carbamylcholine that produced similar degrees of bradycardia (n = 6). Galanin (500 nM) also significantly attenuated the release of 3H-acetylcholine from isolated atria during field stimulation (5 Hz, n = 5). The effect of galanin on vagal bradycardia could be abolished by the galanin receptor antagonist

  9. Plasticity of gastrointestinal vagal afferent satiety signals.

    PubMed

    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.

  10. Plasticity of gastro-intestinal vagal afferent endings.

    PubMed

    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.

  11. Plasticity of vagal brainstem circuits in the control of gastric function

    PubMed Central

    Browning, Kirsteen N.; Travagli, R. Alberto

    2010-01-01

    Background Sensory information from the viscera, including the gastrointestinal (GI) tract, is transmitted through the afferent vagus via a glutamatergic synapse to neurons of the nucleus tractus solitarius (NTS), which integrate this sensory information to regulate autonomic functions and homeostasis. The integrated response is conveyed to, amongst other nuclei, the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) using mainly GABA, glutamate and catecholamines as neurotransmitters. Despite being modulated by almost all the neurotransmitters tested so far, the glutamatergic synapse between NTS and DMV does not appear to be tonically active in the control of gastric motility and tone. Conversely, tonic inhibitory GABAergic neurotransmission from the NTS to the DMV appears critical in setting gastric tone and motility, yet, under basal conditions, this synapse appears resistant to modulation. Purpose Here, we review the available evidence suggesting that vagal efferent output to the GI tract is regulated, perhaps even controlled, in an “on-demand” and efficient manner in response to ever-changing homeostatic conditions. The focus of this review is on the plasticity induced by variations in the levels of second messengers in the brainstem neurons that form vago-vagal reflex circuits. Emphasis is placed upon the modulation of GABAergic transmission to DMV neurons and the modulation of afferent input from the GI tract by neurohormones/neurotransmitters and macronutrients. Derangement of this “on-demand” organization of brainstem vagal circuits may be one of the factors underlying the pathophysiological changes observed in functional dyspepsia or hyperglycemic gastroparesis. PMID:20804520

  12. Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways.

    PubMed Central

    Ricco, M M; Kummer, W; Biglari, B; Myers, A C; Undem, B J

    1996-01-01

    1. The present study addressed the hypothesis that jugular and nodose vagal ganglia contain the somata of functionally and anatomically distinct airway afferent fibres. 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF). In the nodose ganglion, NF-immunoreactive neurones accounted for about 98% of the Fast Blue-labelled cells while in the jugular ganglion they accounted for approximately 48%. SP and NF immunoreactivity was never (n = 100) observed in the same cell suggesting that the antisera labelled distinct populations. 3. Electrophysiological investigations were performed using an in vitro guinea-pig tracheal and bronchial preparation with intact afferent vagal pathways, including nodose and jugular ganglia. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in either ganglion. 4. The nodose ganglion contained the somata of mainly fast-conducting tracheal A delta fibres whereas the jugular ganglion contained equal numbers of C fibre and A delta fibre tracheal afferent somata. The nodose A delta neurones adapted rapidly to mechanical stimulation, had relatively low mechanical thresholds, were not activated by capsaicin and adapted rapidly to a hyperosmotic stimulus. By contrast, jugular A delta and C fibres adapted slowly to mechanical stimulation, were often activated by capsaicin, had higher mechanical thresholds and displayed a slow adaptation to a hyperosmotic stimulus. 5. The anatomical, physiological and pharmacological data provide evidence to support the contention that the vagal ganglionic source of the fibre supplying the airways ultimately dictates its neurochemical and physiological phenotype. Images Figure 1 PMID:8910234

  13. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    PubMed

    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. Moderate Baseline Vagal Tone Predicts Greater Prosociality in Children

    PubMed Central

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

    2016-01-01

    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 association (inverted U-shape curve) between baseline vagal tone and prosociality (Kogan et al., 2014). The present research examined whether this nonlinear association was evident in children. We found consistent evidence for a quadratic relation between vagal tone and prosociality across 3 samples of children using 6 different measures. Compared to low and high vagal tone, moderate vagal tone in early childhood concurrently predicted greater self-reported prosociality (Study 1), observed empathic concern in response to the distress of others and greater generosity toward less fortunate peers (Study 2), and longitudinally predicted greater self-, mother-, and teacher-reported prosociality 5.5 years later in middle childhood (Study 3). Taken together, our findings suggest that moderate vagal tone at rest represents a physiological preparedness or tendency to engage in different forms of prosociality across different contexts. Early moderate vagal tone may reflect an optimal balance of regulation and arousal that helps prepare children to sympathize, comfort, and share with others. PMID:27819463

  15. Moderate Baseline Vagal Tone Predicts Greater Prosociality in Children

    ERIC Educational Resources Information Center

    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…

  16. Infants' and Mothers' Vagal Reactivity in Response to Anger

    ERIC Educational Resources Information Center

    Moore, Ginger A.

    2009-01-01

    Background: Exposure to anger in the family is a risk factor for disruptive behavior disorders characterized by ineffective vagal regulation. Effects of anger on developing vagal regulation may be due to direct exposure or to effects on parents' regulation of emotion as parents support infants' regulation. Little is known about the impact of anger…

  17. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

    PubMed

    Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang

    2013-01-15

    Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

  18. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    PubMed

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  19. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones

    PubMed Central

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-01-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  20. Interparental Relationship Dynamics and Cardiac Vagal Functioning in Infancy

    PubMed Central

    Graham, Alice M.; Ablow, Jennifer C.; Measelle, Jeffrey R.

    2010-01-01

    This study examined associations between interparental relationship dynamics and vagus system functioning in infancy. The functioning of the vagus system, part of the parasympathetic nervous system, indexes emotional reactivity and regulation. Interparental avoidance and dyadic adjustment constitute the focus of this study in order to bring attention to relationship dynamics not subsumed under overt conflict. Infants’ baseline vagal tone and change in vagal tone in response to a novel toy were assessed at five months in a sample of high-risk mother-infant dyads (n = 77). Maternal report of interparental avoidance demonstrated an association with infants’ baseline vagal tone, while interparental dyadic adjustment was associated with change in infants’ vagal tone from baseline to the novel toy. Infant gender moderated these associations. Maternal sensitivity did not mediate interparental relationship dynamics and infants’ vagal functioning. Results are discussed in the context of emotional security theory. PMID:20727595

  1. Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

    PubMed

    Thomas, G R; Thibodeaux, H; Margolius, H S; Webb, J G; Privitera, P J

    1987-07-01

    The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

  2. Differential control of central cardiorespiratory interactions by hypercapnia and the effect of prenatal nicotine.

    PubMed

    Huang, Zheng-Gui; Griffioen, Kathleen J S; Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Bouairi, Euguenia; Mendelowitz, David

    2006-01-04

    Hypercapnia evokes a strong cardiorespiratory response including gasping and a pronounced bradycardia; however, the mechanism responsible for these survival responses initiated in the brainstem is unknown. To examine the effects of hypercapnia on the central cardiorespiratory network, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and inhibitory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Hypercapnia differentially modulated inhibitory neurotransmission to CVNs; whereas hypercapnia selectively depressed spontaneous glycinergic IPSCs in CVNs without altering respiratory-related increases in glycinergic neurotransmission, it decreased both spontaneous and inspiratory-associated GABAergic IPSCs. Because maternal smoking is the highest risk factor for sudden infant death syndrome (SIDS) and prenatal nicotine exposure is proposed to be the link between maternal smoking and SIDS, we examined the cardiorespiratory responses to hypercapnia in animals exposed to nicotine in the prenatal and perinatal period. In animals exposed to prenatal nicotine, hypercapnia evoked an exaggerated depression of GABAergic IPSCs in CVNs with no significant change in glycinergic neurotransmission. Hypercapnia altered inhibitory neurotransmission to CVNs at both presynaptic and postsynaptic sites. Although the results obtained in this study in vitro cannot be extrapolated with certainty to in vivo responses, the results of this study provide a likely neurochemical mechanism for hypercapnia-evoked bradycardia and the dysregulation of this response with exposure to prenatal nicotine, creating a higher risk for SIDS.

  3. Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

    PubMed

    Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

    2012-04-01

    The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. FOOD-INTAKE DYSREGULATION IN TYPE 2 DIABETIC GOTO-KAKIZAKI RATS: HYPOTHESIZED ROLE OF DYSFUNCTIONAL BRAINSTEM THYROTROPIN-RELEASING HORMONE AND IMPAIRED VAGAL OUTPUT

    PubMed Central

    Zhao, K.; Ao, Y.; Harper, R.M.; Go, V. L.W.; Yang, H.

    2013-01-01

    Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56–81% in GK rats. Fasting (48 h) and refeeding (2 h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. PMID:23701881

  5. Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

    PubMed

    Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

    2013-09-05

    Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.

  6. Vagal tone as an index of mental state

    NASA Technical Reports Server (NTRS)

    Porges, Stephen W.

    1988-01-01

    The utility of monitoring oscillations in the heart rate pattern as a window to the brain is discussed as an index of general central nervous system status. Quantification of the amplitude of respiratory sinus arrhythmia provides an accurate index of cardiac vagal tone. A number of studies have demonstrated the validity of this measure; the relationship between flight performance and vagal tone has also been studied. In general, the vagal tone index appears to monitor global states of the central nervous system and may be useful in screening the general state of pilots.

  7. Disrupting vagal feedback affects birdsong motor control.

    PubMed

    Méndez, Jorge M; Dall'asén, Analía G; Goller, Franz

    2010-12-15

    Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.

  8. Disrupting vagal feedback affects birdsong motor control

    PubMed Central

    Méndez, Jorge M.; Dall'Asén, Analía G.; Goller, Franz

    2010-01-01

    Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback. PMID:21113000

  9. A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig

    PubMed Central

    Lundberg, J. M.; Saria, A.; Brodin, E.; Rosell, S.; Folkers, K.

    1983-01-01

    Electrical stimulation of the cervical vagus nerve in anesthetized guinea pigs induced a rapid increase in respiratory insufflation pressure, suggesting increased airway resistance. After intravenous administration of a substance P (SP) antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, the insufflation pressure response to vagal stimulation was reduced by 78% while the cardiovascular effects were unchanged. Histamine receptor-blocking agents were used to inhibit the effects of histamine release induced by the SP-antagonist. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP also reduced the increase in insufflation pressure caused by intravenous SP or capsaicin. The long-lasting noncholinergic contraction of the main and hilus bronchi induced by field stimulation in vitro, as well as the contractile effects of SP and capsaicin, were also blocked by the SP antagonist. The cholinergic contractions and the noncholinergic tracheal relaxation on field stimulation in vitro were, however, not blocked by the antagonist. Vagal stimulation in vivo also increased vascular permeability in the respiratory tract and esophagus, causing a subepithelial edema as indicated by Evans blue extravasation. Previous treatment with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP inhibited the permeability increase induced by both vagus nerve stimulation and exogenous SP. SP release from vagal sensory nerves was indirectly shown by reduction in the bronchial levels of SP after nerve stimulation in vivo. The data suggest that a major portion of the vagally or capsaicin-induced increase in smooth muscle tone is caused by SP release from sensory neurons. In addition, activation of vagal SP-containing sensory nerves induces local edema. Tracheobronchial afferent SP-containing C fibers may thus exert local control of smooth muscle tone and vascular permeability in normal and pathophysiological conditions. Images PMID:6189120

  10. Inhibitory neurotransmission regulates vagal efferent activity and gastric motility

    PubMed Central

    McMenamin, Caitlin A; Travagli, R Alberto

    2016-01-01

    The gastrointestinal tract receives extrinsic innervation from both the sympathetic and parasympathetic nervous systems, which regulate and modulate the function of the intrinsic (enteric) nervous system. The stomach and upper gastrointestinal tract in particular are heavily influenced by the parasympathetic nervous system, supplied by the vagus nerve, and disruption of vagal sensory or motor functions results in disorganized motility patterns, disrupted receptive relaxation and accommodation, and delayed gastric emptying, amongst others. Studies from several laboratories have shown that the activity of vagal efferent motoneurons innervating the upper GI tract is inhibited tonically by GABAergic synaptic inputs from the adjacent nucleus tractus solitarius. Disruption of this influential central GABA input impacts vagal efferent output, hence gastric functions, significantly. The purpose of this review is to describe the development, physiology, and pathophysiology of this functionally dominant inhibitory synapse and its role in regulating vagally determined gastric functions. PMID:27302177

  11. The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

    PubMed

    Reznikov, Leah R; Meyerholz, David K; Abou Alaiwa, Mahmoud H; Kuan, Shin-Ping; Liao, Yan-Shin J; Bormann, Nicholas L; Bair, Thomas B; Price, Margaret; Stoltz, David A; Welsh, Michael J

    2018-04-05

    Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity. As a comparison, we also utilized previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating airway hyperreactivity; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

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

    PubMed Central

    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 anxiety. Conversely, higher levels of anxiety and aggression were associated with increased vagal tone during a cognitive stress task. Findings suggest associations between physiological and self-report of emotion regulation (anxiety control beliefs) and that anxiety and aggression may have specific and non-specific relations with physiological indices of emotion regulation. PMID:24708059

  13. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

    NASA Technical Reports Server (NTRS)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Ha, C. Y.; Eckberg, D. L.

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  14. Alcohol and vagal tone as triggers for paroxysmal atrial fibrillation.

    PubMed

    Mandyam, Mala C; Vedantham, Vasanth; Scheinman, Melvin M; Tseng, Zian H; Badhwar, Nitish; Lee, Byron K; Lee, Randall J; Gerstenfeld, Edward P; Olgin, Jeffrey E; Marcus, Gregory M

    2012-08-01

    Alcohol and vagal activity may be important triggers for paroxysmal atrial fibrillation (PAF), but it remains unknown if these associations occur more often than would be expected by chance alone because of the lack of a comparator group in previous studies. We compared self-reported frequency of these triggers in patients with PAF to those with other supraventricular tachycardias (SVTs). Consecutive consenting patients presenting for electrophysiology procedures at a single university medical center underwent a structured interview regarding arrhythmia triggers. Two hundred twenty-three patients with a documented arrhythmia (133 with PAF and 90 with SVT) completed the survey. After multivariable adjustment, patients with PAF had a 4.42 greater odds (95% confidence interval [CI] 1.35 to 14.44) of reporting alcohol consumption (p = 0.014) and a 2.02 greater odds (95% CI 1.02 to 4.00) of reporting vagal activity (p = 0.044) as an arrhythmia trigger compared to patients with SVT. In patients with PAF, drinking primarily beer was associated with alcohol as a trigger (odds ratio [OR] 4.49, 95% CI 1.41 to 14.28, p = 0.011), whereas younger age (OR 0.68, 95% CI 0.49 to 0.95, p = 0.022) and a family history of AF (OR 5.73, 95% CI 1.21 to 27.23, p = 0.028) each were independently associated with having vagal activity provoke an episode. Patients with PAF and alcohol triggers were more likely to have vagal triggers (OR 10.32, 95% CI 1.05 to 101.42, p = 0.045). In conclusion, alcohol consumption and vagal activity elicit PAF significantly more often than SVT. Alcohol and vagal triggers often were found in the same patients with PAF, raising the possibility that alcohol may precipitate AF by vagal mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Local opiate receptors in the sinoatrial node moderate vagal bradycardia.

    PubMed

    Farias, M; Jackson, K; Stanfill, A; Caffrey, J L

    2001-02-20

    Met-enkephalin-arg-phe (MEAP) interrupts vagal bradycardia when infused into the systemic circulation. This study was designed to locate the opiate receptors functionally responsible for this inhibition. Previous observations suggested that the receptors were most likely located in either intracardiac parasympathetic ganglia or the pre-junctional nerve terminals innervating the sinoatrial node. In this study 10 dogs were instrumented with a microdialysis probe inserted into the sinoatrial node. The functional position of the probe was tested by briefly introducing norepinephrine into the probe producing an increase in heart rate of more than 30 beats/min. Vagal stimulations were conducted at 0.5, 1.2 and 4 Hz during vehicle infusion (saline ascorbate). Cardiovascular responses during vagal stimulation were recorded on-line. MEAP was infused directly into the sinoatrial node via the microdialysis probe. The evaluation of vagal bradycardia was repeated during the nodal application of MEAP, diprenorphine (opiate antagonist), and diprenorphine co-infused with MEAP. MEAP introduced into the sinoatrial node via the microdialysis probe reduced vagal bradycardia by more than half. Simultaneous local nodal blockade of these receptors with the opiate antagonist, diprenorphine, eliminated the effect of MEAP demonstrating the participation by opiate receptors. Systemic infusions of MEAP produced a reduction in vagal bradycardia nearly identical to that observed during nodal administration. When local nodal opiate receptors were blocked with diprenorphine, the systemic effect of MEAP was eliminated. These data lead us to suggest that the opiate receptors responsible for the inhibition of vagal bradycardia are located within the sinoatrial node with few, if any, participating extra-nodal or ganglionic receptors.

  16. Sensory neurons that detect stretch and nutrients in the digestive system

    PubMed Central

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

    2016-01-01

    SUMMARY Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons). Optogenetics, in vivo ganglion imaging, and genetically guided anatomical mapping provide direct links between neuron identity, peripheral anatomy, central anatomy, conduction velocity, response properties in vitro and in vivo, and physiological function. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology. PMID:27238020

  17. Distinct Expression of Phenotypic Markers in Placodes- and Neural Crest-Derived Afferent Neurons Innervating the Rat Stomach.

    PubMed

    Trancikova, Alzbeta; Kovacova, Eva; Ru, Fei; Varga, Kristian; Brozmanova, Mariana; Tatar, Milos; Kollarik, Marian

    2018-02-01

    Visceral pain is initiated by activation of primary afferent neurons among which the capsaicin-sensitive (TRPV1-positive) neurons play an important role. The stomach is a common source of visceral pain. Similar to other organs, the stomach receives dual spinal and vagal afferent innervation. Developmentally, spinal dorsal root ganglia (DRG) and vagal jugular neurons originate from embryonic neural crest and vagal nodose neurons originate from placodes. In thoracic organs the neural crest- and placodes-derived TRPV1-positive neurons have distinct phenotypes differing in activation profile, neurotrophic regulation and reflex responses. It is unknown to whether such distinction exists in the stomach. We hypothesized that gastric neural crest- and placodes-derived TRPV1-positive neurons express phenotypic markers indicative of placodes and neural crest phenotypes. Gastric DRG and vagal neurons were retrogradely traced by DiI injected into the rat stomach wall. Single-cell RT-PCR was performed on traced gastric neurons. Retrograde tracing demonstrated that vagal gastric neurons locate exclusively into the nodose portion of the rat jugular/petrosal/nodose complex. Gastric DRG TRPV1-positive neurons preferentially expressed markers PPT-A, TrkA and GFRα 3 typical for neural crest-derived TRPV1-positive visceral neurons. In contrast, gastric nodose TRPV1-positive neurons preferentially expressed markers P2X 2 and TrkB typical for placodes-derived TRPV1-positive visceral neurons. Differential expression of neural crest and placodes markers was less pronounced in TRPV1-negative DRG and nodose populations. There are phenotypic distinctions between the neural crest-derived DRG and placodes-derived vagal nodose TRPV1-positive neurons innervating the rat stomach that are similar to those described in thoracic organs.

  18. A Transactional Analysis of the Relation between Maternal Sensitivity and Child Vagal Regulation

    ERIC Educational Resources Information Center

    Perry, Nicole B.; Mackler, Jennifer S.; Calkins, Susan D.; Keane, Susan P.

    2014-01-01

    A transactional model examining the longitudinal association between vagal regulation (as indexed by vagal withdrawal) and maternal sensitivity from age 2.5 to age 5.5 was assessed. The sample included 356 children (171 male, 185 female) and their mothers who participated in a laboratory visit at age 2.5, 4.5, and 5.5. Cardiac vagal tone was…

  19. Modulation of the masseteric reflex by gastric vagal afferents.

    PubMed

    Pettorossi, V E

    1983-04-01

    Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

  20. Vagal Afferent Innervation of the Lower Esophageal Sphincter

    PubMed Central

    Powley, Terry L.; Baronowsky, Elizabeth A.; Gilbert, Jared M.; Hudson, Cherie N.; Martin, Felecia N.; Mason, Jacqueline K.; McAdams, Jennifer L.; Phillips, Robert J.

    2013-01-01

    To supply a fuller morphological characterization of the vagal afferents innervating the lower esophageal sphincter (LES), specifically to label vagal terminals in the tissues forming the LES in the gastroesophageal junction, the present experiment employed injections of dextran biotin into the nodose ganglia of rats. Four types of vagal afferents innervated the LES. Clasp and sling muscle fibers were directly and prominently innervated by intramuscular arrays (IMAs). Individual IMA terminals subtended about 16° of arc of the esophageal circumference, and, collectively, the terminal fields were distributed within the muscle ring to establish a 360° annulus of mechanoreceptors in the sphincter wall. 3D morphometry of the terminals established that, compared to sling muscle IMAs, clasp muscle IMAs had more extensive arbors and larger receptive fields. In addition, at the cardia, local myenteric ganglia between smooth muscle sheets and striated muscle bundles were innervated by intraganglionic laminar endings (IGLEs), in a pattern similar to the innervation of the myenteric plexus throughout the stomach and esophagus. Finally, as previously described, the principle bundle of sling muscle fibers that links LES sphincter tissue to the antropyloric region of the lesser curvature was innervated by exceptionally long IMAs as well as by unique web ending specializations at the distal attachment of the bundle. Overall, the specialized varieties of densely distributed vagal afferents innervating the LES underscore the conclusion that these sensory projections are critically involved in generating LES reflexes and may be promising targets for managing esophageal dysfunctions. PMID:23583280

  1. Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence.

    PubMed

    Cheng, Zixi; Zhang, Hong; Guo, Shang Z; Wurster, Robert; Gozal, David

    2004-04-01

    In previous single-labeling experiments, we showed that neurons in the nucleus ambiguous (NA) and the dorsal moto nucleus of the vagus (DmnX) project to intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly in the size of their projection fields, axon caliber, and endings in cardiac ganglia. These differences in NA and DmnX axon cardiac projections raise the question as to whether they target the same, distinct, or overlapping populations of cardiac principal neurons. To address this issue, we examined vagal terminals in cardiac ganglia and trace injection sites in the brain stem using two different anterograde t ace s 1,1-dioleyl-3,3,3,3-tetramethylindocarbocyanine methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide] and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX neurons innervate the same cardiac ganglia, but these axons target separate subpopulations of principal neurons and 2) axons arising from neurons in the NA and DmnX in the contralateral sides of the brain stem enter the cardiac ganglionic plexus through separate bundles and preferentially innervate principal neurons near their entry regions, providing topographic mapping of vagal motor neurons in left and right brain stem vagal nuclei. Because the NA and DmnX project to distinct populations of cardiac principal neurons, we propose that they may play different roles in controlling cardiac function.

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

    PubMed

    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.

  3. Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex.

    PubMed

    Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

    2004-12-15

    Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of L-glutamate at the same sites, and both the effects of L-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure

  4. Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

    PubMed Central

    Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

    2004-01-01

    Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)−1) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to −0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of l-glutamate at the same sites, and both the effects of l-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure

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

    NASA Technical Reports Server (NTRS)

    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.

  6. Reduced cardiac vagal activity in obese children and adolescents.

    PubMed

    Dangardt, Frida; Volkmann, Reinhard; Chen, Yun; Osika, Walter; Mårild, Staffan; Friberg, Peter

    2011-03-01

      Obese children present with various cardiovascular risk factors affecting their future health. In adults, cardiac autonomic function is a major risk factor, predicting cardiovascular morbidity and mortality. We hypothesized that obese children and adolescents had a lower cardiac vagal activity than lean subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS), reflecting the dynamic regulation of cardiac vagal function, in large groups of obese and lean young individuals.   Cardiac BRS, using the sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls) and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared to both overweight and lean subjects [16±7 versus 21±9 (P<0·01) and 22±10 ms per mmHg (P<0·0001), respectively]. The differences remained after correcting for age, gender and pubertal status.   Children with obesity had low vagal activity at rest, and there was no gender difference. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  7. Importance of vagal input in maintaining gastric tone in the dog.

    PubMed Central

    Azpiroz, F; Malagelada, J R

    1987-01-01

    1. Using a gastric barostat to quantify variations in gastric tone, we had previously demonstrated that food ingestion or intestinal nutrient perfusion induces gastric relaxation. These data suggested a basal tonic contraction of the stomach during fasting. 2. To determine the role of vagal input in maintaining fasting gastric tone, we prepared two chronic canine models, either isolating both cervical vagal trunks in a cutaneous tunnel or including the supradiaphragmatic vagi within an implanted cooling jacket. In the fasted conscious dogs, we then studied the effect, on gastric tone, of acute and reversible vagal blockade by cooling. 3. Cervical vagal cooling produced a reversible gastric relaxation and increased the heart rate. Supradiaphragmatic vagal cooling produced a similar gastric relaxation without the cardiac effect. 4. Adrenergic blockade did not change either the base-line gastric tone or the cooling-induced relaxation. Adrenaline decreased gastric tone, but vagal cooling still produced a significant relaxation. 5. Atropine alone or combined with adrenergic antagonists produced a gastric relaxation that was not further increased by vagal cooling. Bethanechol increased gastric tone, an effect unchanged by vagal cooling. 6. We conclude that gastric tone during fasting is maintained by a cholinergic input, which is vagally mediated at both the cervical and the supradiaphragmatic levels. Images Fig. 1 PMID:2888879

  8. Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.

    PubMed

    Biddinger, Jessica E; Fox, Edward A

    2014-07-30

    Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.

  9. Parental Socialization, Vagal Regulation, and Preschoolers' Anxious Difficulties: Direct Mothers and Moderated Fathers

    ERIC Educational Resources Information Center

    Hastings, Paul D.; Sullivan, Caroline; McShane, Kelly E.; Coplan, Robert J.; Utendale, William T.; Vyncke, Johanna D.

    2008-01-01

    Parental supportiveness and protective overcontrol and preschoolers' parasympathetic regulation were examined as predictors of temperamental inhibition, social wariness, and internalizing problems. Lower baseline vagal tone and weaker vagal suppression were expected to mark poorer dispositional self-regulatory capacity, leaving children more…

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

    PubMed

    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.

  11. Longitudinal relations between child vagal tone and parenting behavior: 2 to 4 years.

    PubMed

    Kennedy, Amy E; Rubin, Kenneth H; Hastings, Paul D; Maisel, Beth

    2004-07-01

    The longitudinal relations between physiological markers of child emotion regulation and maternal parenting practices were examined from 2 to 4 years of age. At Time 1, cardiac vagal tone was assessed for one hundred four 2-year-olds (54 females); their mothers completed an assessment of parenting styles. Two years later, at Time 2, 84 of the original participants were reassessed on measures of cardiac vagal tone and parenting style. Results indicated both baseline cardiac vagal tone and maternal parenting practices to be stable from 2 to 4 years of age. Children's cardiac vagal tone predicted specific parenting practices from the toddler to preschool years. Further, child cardiac vagal tone moderated maternal restrictive-parenting practices from 2 to 4 years of age; mothers of children who were highly or moderately physiologically dysregulated were more likely to report restrictive parenting practices at both 2 and 4 years of age. Copyright 2004 Wiley Periodicals, Inc.

  12. Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

    PubMed Central

    Torres-Rosas, Rafael; Yehia, Ghassan; Peña, Geber; Mishra, Priya; del Rocio Thompson-Bonilla, Maria; Moreno-Eutimio, Mario Adán; Arriaga-Pizano, Lourdes Andrea; Isibasi, Armando; Ulloa, Luis

    2014-01-01

    Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders. PMID:24562381

  13. Reflex anoxic seizures ('white breath-holding'): nonepileptic vagal attacks.

    PubMed Central

    Stephenson, J B

    1978-01-01

    From clinical history 58 children were diagnosed as having reflex anoxic seizures secondary to provoked cardioinhibition (also known as white breath-holding attacks). Before referral, these seizures were commonly misdiagnosed as epileptic either because the provocation was ignored, not recognised, or was a febrile illness, or because there was no crying, no obvious breath-holding, little cyanosis, and often no pallor to suggest syncope and cerebral ischaemia. The duration of cardiac asystole after ocular compression was measured in these children and in 60 additional children with other paroxysmal disorders. In 45 (78%) of the 58 with reflex anoxic seizures asystole was 2 seconds or over, and in 32 (55%) it was 4 seconds or greater, an abnormal response. Review of the literature supports the concept that these seizures result from vagal-mediated reflex cardiac arrest which can if necessary be prevented by atropine. The simple name 'vagal attack' is proposed. Ocular compression under EEG and ECG control supports the clinical diagnosis if asystole and/or an anoxic seizure is induced; the procedure described is safe and should be routine in seizure or syncope evaluation, when a meticulous history still leaves room for doubt. Images Figs. 1-8 p194-b p194-c p194-d p194-e p194-f p194-g p194-h PMID:348123

  14. Distribution of AMPA receptor subunits GluR1-4 in the dorsal vagal complex of the rat: a light and electron microscope immunocytochemical study.

    PubMed

    Kessler, J P; Baude, A

    1999-10-01

    The dorsal vagal complex, localized in the dorsomedial medulla, includes the nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve (DMN) and the area postrema (AP). The distribution of AMPA-preferring glutamate receptors (AMPA receptors) within this region was investigated using immunohistochemistry and antibodies recognizing either one (GluR1 or GluR4) or two (GluR2 and GluR3) AMPA receptors subunits. The distribution of GluR1 immunoreactivity showed high contrast of staining between strongly and lightly labeled areas. Labeling was intense in the AP and weak in the NTS, except for its medial and dorsalmost parts which exhibited moderate staining. Almost no GluR1 immunoreactivity was found in the DMN. GluR2/3 immunolabeling was present in the entire dorsal vagal complex. This labeling was strong in the AP, the DMN and the medial half of the NTS and moderate in the lateral half of the NTS, except for the interstitial subdivision which exhibited intense staining. Labeling induced by the GluR4 antibody was very weak throughout the dorsal vagal complex. Ultrastructural examination showed that GluR1 and GluR2/3 immunoreactivity was localized in neuronal cell bodies and dendrites. No labeled axon terminal or glial cell body was found. Immunoperoxidase staining in labeled cell bodies and dendrites was associated with intracellular organelles (microtubules, mitochondria, cisternae of the endoplasmic reticulum,.) and/or parts of the plasma membrane. Plasma membrane labeling was often associated with asymmetrical synaptic differentiations. No labeled symmetrical synapse was found using either GluR1 or GluR2/3 antibody. The present results show that AMPA receptors have a widespread distribution in neuronal perikarya and dendrites of the rat dorsal vagal complex. They suggest differences in subunit composition between AMPA receptors localized in the NTS, the DMN and the AP. Ultrastructural data are consistent with the fact that AMPA receptors associated

  15. Modulation of experimental arthritis by vagal sensory and central brain stimulation.

    PubMed

    Bassi, Gabriel Shimizu; Dias, Daniel Penteado Martins; Franchin, Marcelo; Talbot, Jhimmy; Reis, Daniel Gustavo; Menezes, Gustavo Batista; Castania, Jaci Airton; Garcia-Cairasco, Norberto; Resstel, Leonardo Barbosa Moraes; Salgado, Helio Cesar; Cunha, Fernando Queiróz; Cunha, Thiago Mattar; Ulloa, Luis; Kanashiro, Alexandre

    2017-08-01

    Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The antiarrhythmic effect of vagal stimulation after acute coronary occlusion: Role of the heart rate.

    PubMed

    Manati, Waheed; Pineau, Julien; Doñate Puertas, Rosa; Morel, Elodie; Quadiri, Timour; Bui-Xuan, Bernard; Chevalier, Philippe

    2018-01-03

    Strong evidence suggests a causal link between autonomic disturbances and ventricular arrhythmias. However, the mechanisms underlying the antiarrhythmic effect of vagal stimulation are poorly understood. The vagal antiarrhythmic effect might be modulated by a decrease in heart rate. the proximal anterior interventricular artery was occluded in 16 pigs by clamping under general anaesthesia. Group 1: heart rates remained spontaneous (n = 6; 12 occlusions); Group 2: heart rates were fixed at 190 beats per minute (bpm) with atrial electrical stimulation (n = 10; 20 occlusions). Each pig received two occlusions, 30 min apart, one without and one with vagal stimulation (10 Hz, 2 ms, 5-20 mA). The antiarrhythmic effect of vagal activation was defined as the time to the appearance of ventricular fibrillation (VF) after occlusion. In Group 1, vagal stimulation triggered a significant decrease in basal heart rate (132 ± 4 vs. 110 ± 17 bpm, p < 0.05), and delayed the time to VF after coronary occlusion (1102 ± 85 vs. 925 ± 41 s, p < 0.05). In Group 2, vagal stimulation did not modify the time to VF (103 ± 39 vs. 91 ± 20 s). Analyses revealed that heart rate and the time to VF were positively linearly related. Maintaining a constant heart rate with atrial electrical stimulation in pigs prevented vagal stimulation from modifying the time to VF after acute coronary occlusion.

  17. Pharmacology of Vagal Afferent Influences on Disordered Breathing During Sleep

    PubMed Central

    Carley, David W; Radulovacki, Miodrag

    2008-01-01

    Sleep related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of ∼2% of women and ∼4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. Current primary treatments are surgical or mechanical, with no drug treatments available. Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved. PMID:18694851

  18. Thoracoscopic sympathectomy increases efferent cardiac vagal activity and baroreceptor sensitivity.

    PubMed

    Bygstad, Elisabeth; Terkelsen, Astrid J; Pilegaard, Hans K; Hansen, John; Mølgaard, Henning; Hjortdal, Vibeke E

    2013-09-01

    Thoracoscopic sympathectomy at levels T2 or T2-T3 is a treatment for focal hyperhidrosis and facial blushing. These levels of the sympathetic trunk innervate the heart, and consequently, the procedure is reported to change the heart rate variability due to changes in efferent cardiac autonomic activity. Our objective was to investigate the effects of thoracoscopic sympathectomy on global autonomic control, including baroreceptor sensitivity. Eight patients (6 F, median age 28 years [range 20-58 years]) were exposed to the tilt-table test and cardiopulmonary exercise test before, and 3 months after, thoracoscopic sympathectomy. Eight healthy age-, gender- and BMI-matched controls were used as controls and underwent the same tests once. During tilt-table testing electrocardiogram, blood pressure, impedance cardiography and respiration were measured continuously, and efferent cardiac autonomic balance was estimated. The heart rate measured during orthostatic stress test was lowered after thoracoscopic sympathectomy (between-group; P = 0.01) due to a change in autonomic tone, with increased vagal (high-frequency power n.u.; P = 0.001), and reduced sympathetic efferent cardiac activity (low-frequency power n.u.; P < 0.001). Baroreceptor sensitivity measured during rest was increased (26 ± 13 vs 44 ± 19 ms/mmHg; P = 0.01), and diastolic blood pressure reduced after surgery (P = 0.01). The increases in systolic blood pressure and the sympathetic marker CCV-LF in response to orthostatic stress were higher before sympathectomy, with almost no increases post-surgically (condition × group interaction; P = 0.01 and P = 0.001, respectively). We found no change in post-procedure exercise capacity, although patients had a lower peak VO2 and maximal cardiac index than controls. Thoracoscopic sympathectomy changes the autonomic tone towards increased vagal activity; this is potentially cardioprotective. To our knowledge, this is the first study to show increased baroreceptor

  19. Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit.

    PubMed

    Delpierre, S; Pugnat, C; Duté, N; Jammes, Y

    1995-02-15

    It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition.

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

    PubMed Central

    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 <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. PMID:20126345

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

    PubMed

    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.

  2. The modulatory effects of noradrenaline on vagal control of heart rate in the dogfish, Squalus acanthias.

    PubMed

    Agnisola, Claudio; Randall, David J; Taylor, Edwin W

    2003-01-01

    The possible interactions between inhibitory vagal control of the heart and circulating levels of catecholamines in dogfish (Squalus acanthias) were studied using an in situ preparation of the heart, which retained intact its innervation from centrally cut vagus nerves. The response to peripheral vagal stimulation typically consisted of an initial cardiac arrest, followed by an escape beat, leading to renewed beating at a mean heart rate lower than the prestimulation rate (partial recovery). Cessation of vagal stimulation led to a transient increase in heart rate, above the prestimulation rate. This whole response was completely abolished by 10(-4) M atropine (a muscarinic cholinergic antagonist). The degree of vagal inhibition was evaluated in terms of both the initial, maximal cardiac interval and the mean heart rate during partial recovery, both expressed as a percentage of the prestimulation heart rate. The mean prestimulation heart rate of this preparation (36+/-4 beats min(-1)) was not affected by noradrenaline but was significantly reduced by 10(-4) M nadolol (a beta-adrenergic receptor antagonist), suggesting the existence of a resting adrenergic tone arising from endogenous catecholamines. The degree of vagal inhibition of heart rate varied with the rate of stimulation and was increased by the presence of 10(-8) M noradrenaline (the normal in vivo level in routinely active fish), while 10(-7) M noradrenaline (the in vivo level measured in disturbed or deeply hypoxic fish) reduced the cardiac response to vagal stimulation. In the presence of 10(-7) M noradrenaline, 10(-4) M nadolol further reduced the vagal response, while 10(-4) M nadolol + 10(-4) M phentolamine had no effect, indicating a complex interaction between adrenoreceptors, possibly involving presynaptic modulation of vagal inhibition.

  3. Cardiac vagal flexibility and accurate personality impressions: Examining a physiological correlate of the good judge.

    PubMed

    Human, Lauren J; Mendes, Wendy Berry

    2018-02-23

    Research has long sought to identify which individuals are best at accurately perceiving others' personalities or are good judges, yet consistent predictors of this ability have been difficult to find. In the current studies, we revisit this question by examining a novel physiological correlate of social sensitivity, cardiac vagal flexibility, which reflects dynamic modulation of cardiac vagal control. We examined whether greater cardiac vagal flexibility was associated with forming more accurate personality impressions, defined as viewing targets more in line with their distinctive self-reported profile of traits, in two studies, including a thin-slice video perceptions study (N = 109) and a dyadic interaction study (N = 175). Across studies, we found that individuals higher in vagal flexibility formed significantly more accurate first impressions of others' more observable personality traits (e.g., extraversion, creativity, warmth). These associations held while including a range of relevant covariates, including cardiac vagal tone, sympathetic activation, and gender. In sum, social sensitivity as indexed by cardiac vagal flexibility is linked to forming more accurate impressions of others' observable traits, shedding light on a characteristic that may help to identify the elusive good judge and providing insight into its neurobiological underpinnings. © 2018 Wiley Periodicals, Inc.

  4. Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine

    NASA Technical Reports Server (NTRS)

    Rudas, L.; Crossman, A. A.; Morillo, C. A.; Halliwill, J. R.; Tahvanainen, K. U.; Kuusela, T. A.; Eckberg, D. L.

    1999-01-01

    We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

  5. Breathing exercises with vagal biofeedback may benefit patients with functional dyspepsia.

    PubMed

    Hjelland, Ina E; Svebak, Sven; Berstad, Arnold; Flatabø, Geir; Hausken, Trygve

    2007-09-01

    Many patients with functional dyspepsia (FD) have postprandial symptoms, impaired gastric accommodation and low vagal tone. The aim of this study was to improve vagal tone, and thereby also drinking capacity, intragastric volume and quality of life, using breathing exercises with vagal biofeedback. Forty FD patients were randomized to either a biofeedback group or a control group. The patients received similar information and care. Patients in the biofeedback group were trained in breathing exercises, 6 breaths/min, 5 min each day for 4 weeks, using specially designed software for vagal biofeedback. Effect variables included maximal drinking capacity using a drink test (Toro clear meat soup 100 ml/min), intragastric volume at maximal drinking capacity, respiratory sinus arrhythmia (RSA), skin conductance (SC) and dyspepsia-related quality of life scores. Drinking capacity and quality of life improved significantly more in the biofeedback group than in the control group (p=0.02 and p=0.01) without any significant change in baseline autonomic activity (RSA and SC) or intragastric volume. After the treatment period, RSA during breathing exercises was significantly correlated to drinking capacity (r=0.6, p=0.008). Breathing exercises with vagal biofeedback increased drinking capacity and improved quality of life in FD patients, but did not improve baseline vagal tone.

  6. Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms.

    PubMed

    Faris, Patricia L; Eckert, Elke D; Kim, Suck-Won; Meller, William H; Pardo, Jose V; Goodale, Robert L; Hartman, Boyd K

    2006-05-01

    The bilateral vagus nerves (Cranial X) provide both afferent and efferent connections between the viscera and the caudal medulla. The afferent branches increasingly are being recognized as providing significant input to the central nervous system for modulation of complex behaviors. In this paper, we review evidence from our laboratory that increases in vagal afferent activity are involved in perpetuating binge-eating and vomiting in bulimia nervosa. Preliminary findings are also presented which suggest that a subgroup of depressions may have a similar pathophysiology. Two main approaches were used to study the role of vagal afferents. Ondansetron (ONDAN), a 5-HT3 antagonist, was used as a pharmacological tool for inhibiting or reducing vagal afferent neurotransmission. Second, somatic pain detection thresholds were assessed for monitoring a physiological process known to be modulated by vagal afferents, including the gastric branches involved in meal termination and satiety. High levels of vagal activity result in an increase in pain detection thresholds. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Positron Emission Tomography (PET) was used to identify higher cortical brain areas activated by vagal stimulation produced by proximal gastric distention in normal eating subjects. Double-blind treatment of severe bulimia nervosa subjects with ONDAN resulted in a rapid and significant decrease in binge-eating and vomiting compared to placebo controls. The decrease in abnormal eating episodes was accompanied by a return of normal satiety. Pain detection thresholds measured weekly over the course of the treatment protocol were found to dynamically fluctuate in association with bulimic episodes. Thresholds were the most elevated during periods of short-term abstinence from the behaviors, suggesting that not engaging in a binge/vomit episode is accompanied by an increase in vagal activity. ONDAN also resulted in abolition of the

  7. Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl.

    PubMed

    Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

    2018-01-01

    Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal-bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

  8. Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl

    PubMed Central

    Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

    2018-01-01

    Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal–bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER. PMID:29867575

  9. Different role of TTX-sensitive voltage-gated sodium channel (NaV 1) subtypes in action potential initiation and conduction in vagal airway nociceptors.

    PubMed

    Kollarik, M; Sun, H; Herbstsomer, R A; Ru, F; Kocmalova, M; Meeker, S N; Undem, B J

    2018-04-15

    The action potential initiation in the nerve terminals and its subsequent conduction along the axons of afferent nerves are not necessarily dependent on the same voltage-gated sodium channel (Na V 1) subunits. The action potential initiation in jugular C-fibres within airway tissues is not blocked by TTX; nonetheless, conduction of action potentials along the vagal axons of these nerves is often dependent on TTX-sensitive channels. This is not the case for nodose airway Aδ-fibres and C-fibres, where both action potential initiation and conduction is abolished by TTX or selective Na V 1.7 blockers. The difference between the initiation of action potentials within the airways vs. conduction along the axons should be considered when developing Na V 1 blocking drugs for topical application to the respiratory tract. The action potential (AP) initiation in the nerve terminals and its subsequent AP conduction along the axons do not necessarily depend on the same subtypes of voltage-gated sodium channels (Na V 1s). We evaluated the role of TTX-sensitive and TTX-resistant Na V 1s in vagal afferent nociceptor nerves derived from jugular and nodose ganglia innervating the respiratory system. Single cell RT-PCR was performed on vagal afferent neurons retrogradely labelled from the guinea pig trachea. Almost all of the jugular neurons expressed the TTX-sensitive channel Na V 1.7 along with TTX-resistant Na V 1.8 and Na V 1.9. Tracheal nodose neurons also expressed Na V 1.7 but, less frequently, Na V 1.8 and Na V 1.9. Na V 1.6 were expressed in ∼40% of the jugular and 25% of nodose tracheal neurons. Other Na V 1 α subunits were only rarely expressed. Single fibre recordings were made from the vagal nodose and jugular nerve fibres innervating the trachea or lung in the isolated perfused vagally-innervated preparations that allowed for selective drug delivery to the nerve terminal compartment (AP initiation) or to the desheathed vagus nerve (AP conduction). AP initiation in

  10. Optogenetic and pharmacological evidence that somatostatin-GABA neurons are important regulators of parasympathetic outflow to the stomach.

    PubMed

    Lewin, Amanda E; Vicini, Stefano; Richardson, Janell; Dretchen, Kenneth L; Gillis, Richard A; Sahibzada, Niaz

    2016-05-15

    The dorsal motor nucleus of the vagus (DMV) in the brainstem consists primarily of vagal preganglionic neurons that innervate postganglionic neurons of the upper gastrointestinal tract. The activity of the vagal preganglionic neurons is predominantly regulated by GABAergic transmission in the DMV. The present findings indicate that the overwhelming GABAergic drive present at the DMV is primarily from somatostatin positive GABA (Sst-GABA) DMV neurons. Activation of both melanocortin and μ-opioid receptors at the DMV inhibits Sst-GABA DMV neurons. Sst-GABA DMV neurons may serve as integrative targets for modulating vagal output activity to the stomach. We have previously shown that local GABA signalling in the brainstem is an important determinant of vagally-mediated gastric activity. However, the neural identity of this GABA source is currently unknown. To determine this, we focused on the somatostatin positive GABA (Sst-GABA) interneuron in the dorsal motor nucleus of the vagus (DMV), a nucleus that is intimately involved in regulating gastric activity. Also of particular interest was the effect of melanocortin and μ-opioid agonists on neural activity of Sst-GABA DMV neurons because their in vivo administration in the DMV mimics GABA blockade in the nucleus. Experiments were conducted in brain slice preparation of transgenic adult Sst-IRES-Cre mice expressing tdTomato fluorescence, channelrhodopsin-2, archaerhodopsin or GCaMP3. Electrophysiological recordings were obtained from Sst-GABA DMV neurons or DiI labelled gastric-antrum projecting DMV neurons. Our results show that optogenetic stimulation of Sst-GABA neurons results in a robust inhibition of action potentials of labelled premotor DMV neurons to the gastric-antrum through an increase in inhibitory post-synaptic currents. The activity of the Sst-GABA neurons in the DMV is inhibited by both melanocortin and μ-opioid agonists. These agonists counteract the pronounced inhibitory effect of Sst-GABA neurons on

  11. Neuroanatomical basis of Sandifer's syndrome: a new vagal reflex?

    PubMed

    Cerimagic, Denis; Ivkic, Goran; Bilic, Ervina

    2008-01-01

    Sandifer's syndrome is a gastrointestinal disorder with neurological features. It is characterized by reflex torticollis following deglutition in patients with gastroesophageal reflux and/or hiatal hernia. The authors believe that neurological manifestations of the syndrome are the consequence of vagal reflex with the reflex center in nucleus tractus solitarii (NTS). Three models for the neuroanatomical basis of the hypothetic reflex arc are presented. In the first one the hypothetic reflex arc is based on the classic hypothesis of two components nervus accessorius (n.XI) - radix cranialis (RC) and radix spinalis (RS) The nervous impulses are transmitted by nervus vagus (n.X) general visceral afferent (GVA) fibers to NTS situated in medulla oblongata, then by interneuronal connections on nucleus ambiguus (NA) and nucleus dorsalis nervi vagi (NDX). Special visceral efferent fibers (SVE) impulses from NA are in part transferred to n.XI ramus externus (RE) (carrying the majority of general somatic efferent (GSE) fibers) via hypothetic anastomoses in the region of foramen jugulare. This leads to contraction of trapezius and sternocleidomastoideus muscles, and the occurrence of intermittent torticollis. In the second suggested neuroanatomical model the hypothetic reflex arc is organized in the absence of n.XI RC, the efferent part of the reflex arc continues as NA, which is motor nucleus of nervus glossopharyngeus (n.IX) and n.X in this case while distal roots of n.XI that appear at the level of the olivary nucleus lower edge represent n.X roots. In the third presented model the hypothetic reflex arc includes no jugular transfer and could be realized via interneuronal connections directly from NTS to the spinal motoneurons within nucleus radicis spinalis nervi accessorii (NRS n.XI) or from NA to NRS n.XI. The afferent segment of the postulated reflex arc in all three models is mediated via n.X. We conclude that Sandifer's syndrome is a clinical manifestation of another

  12. The contribution of coping related variables and cardiac vagal activity on the performance of a dart throwing task under pressure.

    PubMed

    Mosley, Emma; Laborde, Sylvain; Kavanagh, Emma

    2017-10-01

    The aims of this study were 1) to assess the predictive role of coping related variables (CRV) on cardiac vagal activity (derived from heart rate variability), and 2) to investigate the influence of CRV (including cardiac vagal activity) on a dart throwing task under low pressure (LP) and high pressure (HP) conditions. Participants (n=51) completed trait CRV questionnaires: Decision Specific Reinvestment Scale, Movement Specific Reinvestment Scale and Trait Emotional Intelligence Questionnaire. They competed in a dart throwing task under LP and HP conditions. Cardiac vagal activity measurements were taken at resting, task and during recovery for 5min. Self-reported ratings of stress were recorded at three time points via a visual analogue scale. Upon completion of the task, self-report measures of motivation, stress appraisal, attention, perceived pressure and dart throwing experience were completed. Results indicated that resting cardiac vagal activity had no predictors. Task cardiac vagal activity was predicted by resting cardiac vagal activity in both pressure conditions with the addition of a trait CRV in HP. Post task cardiac vagal activity was predicted by resting cardiac vagal activity in both conditions with the addition of a trait CRV in HP. Cardiac vagal reactivity (difference from resting to task) was predicted by a trait CRV in HP conditions. Cardiac vagal recovery (difference from task to post task) was predicted by a state CRV only in LP. Dart throwing task performance was predicted by a combination of both CRV and cardiac vagal activity. The current research suggests that coping related variables and cardiac vagal activity influence dart throwing task performance differently dependent on pressure condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. High job control enhances vagal recovery in media work.

    PubMed

    Lindholm, Harri; Sinisalo, Juha; Ahlberg, Jari; Jahkola, Antti; Partinen, Markku; Hublin, Christer; Savolainen, Aslak

    2009-12-01

    Job strain has been linked to increased risk of cardiovascular diseases. In modern media work, time pressures, rapidly changing situations, computer work and irregular working hours are common. Heart rate variability (HRV) has been widely used to monitor sympathovagal balance. Autonomic imbalance may play an additive role in the development of cardiovascular diseases. To study the effects of work demands and job control on the autonomic nervous system recovery among the media personnel. From the cross-sectional postal survey of the employees in Finnish Broadcasting Company (n = 874), three age cohorts (n = 132) were randomly selected for an analysis of HRV in 24 h electrocardiography recordings. In the middle-aged group, those who experienced high job control had significantly better vagal recovery than those with low or moderate control (P < 0.01). Among young and ageing employees, job control did not associate with autonomic recovery. High job control over work rather than low demands seemed to enhance autonomic recovery in middle-aged media workers. This was independent of poor health habits such as smoking, physical inactivity or alcohol consumption.

  14. Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity.

    PubMed

    Horn, Charles C; Murat, Chloé; Rosazza, Matthew; Still, Liz

    2011-10-24

    Until recently, sensory nerve pathways from the stomach to the brain were thought to detect distension and play little role in nutritional signaling. Newer data have challenged this view, including reports on the presence of taste receptors in the gastrointestinal lumen and the stimulation of multi-unit vagal afferent activity by glutamate infusions into the stomach. However, assessing these chemosensory effects is difficult because gastric infusions typically evoke a distension-related vagal afferent response. In the current study, we recorded gastric vagal afferent activity in the rat to investigate the possibility that umami (glutamate, 150 mM) and bitter (denatonium, 10 mM) responses could be dissociated from distension responses by adjusting the infusion rate and opening or closing the drainage port in the stomach. Slow infusions of saline (5 ml over 2 min, open port) produced no significant effects on vagal activity. Using the same infusion rate, glutamate or denatonium solutions produced little or no effects on vagal afferent activity. In an attempt to reproduce a prior report that showed distention and glutamate responses, we produced a distension response by closing the exit port. Under this condition, response to the infusion of glutamate or denatonium was similar to saline. In summary, we found little or no effect of gastric infusion of glutamate or denatonium on gastric vagal afferent activity that could be distinguished from distension responses. The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. The effect of vagal afferent on total vascular compliance in rats.

    PubMed

    Kinoshita, T

    1993-04-01

    This study was designed to investigate the effect of vagal afferent stimulation on total vascular compliance (TVC). Rats were anesthetized with sodium pentobarbital and artificially ventilated, TVC was determined together with stressed and unstressed blood volumes by measuring mean circulatory filling pressure (Pmcf) at three different levels of circulating blood volume. Measurements was repeated with the intact vagus, after vagotomy and during stimulation of vagal afferents. Vagotomy caused no change in TVC, Pmcf, and stressed and unstressed blood volumes. On the other hand, electrical stimulation of the vagal afferents for 30 sec increased TVC from 3.03 +/- 0.51 to 3.39 +/- 0.44 ml.mmHg(-1).kg(-1) (P < 0.05) and decreased Pmcf from 7.83 +/- 1.40 to 7.22 +/- 1.21 mmHg (P < 0.05). Neither stressed nor unstressed blood volume was changed by vagal stimulation. These results indicate that excitation of vagal afferent causes venodilation and increases TVC without changing stressed and unstressed blood volumes.

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

    PubMed Central

    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

  17. Vagal activity is quadratically related to prosocial traits, prosocial emotions, and observer perceptions of prosociality.

    PubMed

    Kogan, Aleksandr; Oveis, Christopher; Carr, Evan W; Gruber, June; Mauss, Iris B; Shallcross, Amanda; Impett, Emily A; van der Lowe, Ilmo; Hui, Bryant; Cheng, Cecilia; Keltner, Dacher

    2014-12-01

    In the present article, we introduce the quadratic vagal activity-prosociality hypothesis, a theoretical framework for understanding the vagus nerve's involvement in prosociality. We argue that vagus nerve activity supports prosocial behavior by regulating physiological systems that enable emotional expression, empathy for others' mental and emotional states, the regulation of one's own distress, and the experience of positive emotions. However, we contend that extremely high levels of vagal activity can be detrimental to prosociality. We present 3 studies providing support for our model, finding consistent evidence of a quadratic relationship between respiratory sinus arrhythmia--the degree to which the vagus nerve modulates the heart rate--and prosociality. Individual differences in vagal activity were quadratically related to prosocial traits (Study 1), prosocial emotions (Study 2), and outside ratings of prosociality by complete strangers (Study 3). Thus, too much or too little vagal activity appears to be detrimental to prosociality. The present article provides the 1st theoretical and empirical account of the nonlinear relationship between vagal activity and prosociality.

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

    PubMed Central

    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

  19. Vagal Activity During Physiological Sexual Arousal in Women With and Without Sexual Dysfunction.

    PubMed

    Stanton, Amelia M; Pulverman, Carey S; Meston, Cindy M

    2017-01-02

    Recently, heart rate variability (HRV) level has been found to be a risk factor for female sexual dysfunction. Low HRV was a significant predictor of female sexual arousal dysfunction and overall sexual dysfunction. Building upon this finding, the present study examined whether differences in vagal activity between sexually functional and sexually dysfunctional women may be driving the association between low HRV and female sexual dysfunction. Specifically, respiratory sinus arrhythmia (RSA) was assessed before, during, and after physiological sexual arousal in 84 women, aged 18 to 47, to examine potential differences in vagal activity between sexually functional and sexually dysfunctional women. Significant differences in vagal activity between these two groups were observed (p =.02). These findings provide additional specificity to the recently established relationship between HRV and female sexual function while also proposing a mechanism to target during treatments for sexual dysfunction.

  20. Sluggish vagal brake reactivity to physical exercise challenge in children with selective mutism.

    PubMed

    Heilman, Keri J; Connolly, Sucheta D; Padilla, Wendy O; Wrzosek, Marika I; Graczyk, Patricia A; Porges, Stephen W

    2012-02-01

    Cardiovascular response patterns to laboratory-based social and physical exercise challenges were evaluated in 69 children and adolescents, 20 with selective mutism (SM), to identify possible neurophysiological mechanisms that may mediate the behavioral features of SM. Results suggest that SM is associated with a dampened response of the vagal brake to physical exercise that is manifested as reduced reactivity in heart rate and respiration. Polyvagal theory proposes that the regulation of the vagal brake is a neurophysiological component of an integrated social engagement system that includes the neural regulation of the laryngeal and pharyngeal muscles. Within this theoretical framework, sluggish vagal brake reactivity may parallel an inability to recruit efficiently the structures involved in speech. Thus, the findings suggest that dampened autonomic reactivity during mobilization behaviors may be a biomarker of SM that can be assessed independent of the social stimuli that elicit mutism.

  1. Parenting stressors and young adolescents' depressive symptoms: Does high vagal suppression offer protection?

    PubMed

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

    2017-03-01

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Gene-Environment Contributions to the Development of Infant Vagal Reactivity: The Interaction of Dopamine and Maternal Sensitivity

    ERIC Educational Resources Information Center

    Propper, Cathi; Moore, Ginger A.; Mills-Koonce, W. Roger; Halpern, Carolyn Tucker; Hill-Soderlund, Ashley L.; Calkins, Susan D.; Carbone, Mary Anna; Cox, Martha

    2008-01-01

    This study investigated dopamine receptor genes ("DRD2" and "DRD4") and maternal sensitivity as predictors of infant respiratory sinus arrhythmia (RSA) and RSA reactivity, purported indices of vagal tone and vagal regulation, in a challenge task at 3, 6, and 12 months in 173 infant-mother dyads. Hierarchical linear modeling (HLM) revealed that at…

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

    PubMed Central

    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 < 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 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

  4. Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation

    PubMed Central

    Biddinger, Jessica E.; Baquet, Zachary C.; Jones, Kevin R.; McAdams, Jennifer

    2013-01-01

    A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior. Meal-induced c-Fos activation was reduced in the solitary tract nucleus and area postrema in mice with a smooth muscle-specific NT-3 knockout (SM-NT-3KO) compared with controls, suggesting a decrease in vagal afferent signaling. Daily food intake and body weight of SM-NT-3KO mice and controls were similar. Meal pattern analysis revealed that mutants, however, had increases in average and total daily meal duration compared with controls. Mutants maintained normal meal size by decreasing eating rate compared with controls. Although microstructural analysis did not reveal a decrease in the rate of decay of eating in SM-NT-3KO mice, they ate continuously during the 30-min meal, whereas controls terminated feeding after 22 min. This led to a 74% increase in first daily meal size of SM-NT-3KO mice compared with controls. The increases in meal duration and first meal size of SM-NT-3KO mice are consistent with reduced satiation signaling by vagal afferents. This is the first demonstration of a role for GI NT-3 in short-term controls of feeding, most likely involving effects on development of vagal GI afferents that regulate satiation. PMID:24068045

  5. Voluntary control of breathing does not alter vagal modulation of heart rate

    NASA Technical Reports Server (NTRS)

    Patwardhan, A. R.; Evans, J. M.; Bruce, E. N.; Eckberg, D. L.; Knapp, C. F.

    1995-01-01

    Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.

  6. Central vagal sensory and motor connections: human embryonic and fetal development.

    PubMed

    Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

    2004-07-30

    The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

  7. Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.

    PubMed

    Yang, H; Taché, Y

    1997-05-01

    Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

  8. Optogenetic and pharmacological evidence that somatostatin‐GABA neurons are important regulators of parasympathetic outflow to the stomach

    PubMed Central

    Lewin, Amanda E.; Vicini, Stefano; Richardson, Janell; Dretchen, Kenneth L.; Gillis, Richard A.

    2016-01-01

    Key points The dorsal motor nucleus of the vagus (DMV) in the brainstem consists primarily of vagal preganglionic neurons that innervate postganglionic neurons of the upper gastrointestinal tract.The activity of the vagal preganglionic neurons is predominantly regulated by GABAergic transmission in the DMV.The present findings indicate that the overwhelming GABAergic drive present at the DMV is primarily from somatostatin positive GABA (Sst‐GABA) DMV neurons.Activation of both melanocortin and μ‐opioid receptors at the DMV inhibits Sst‐GABA DMV neurons.Sst‐GABA DMV neurons may serve as integrative targets for modulating vagal output activity to the stomach. Abstract We have previously shown that local GABA signalling in the brainstem is an important determinant of vagally‐mediated gastric activity. However, the neural identity of this GABA source is currently unknown. To determine this, we focused on the somatostatin positive GABA (Sst‐GABA) interneuron in the dorsal motor nucleus of the vagus (DMV), a nucleus that is intimately involved in regulating gastric activity. Also of particular interest was the effect of melanocortin and μ‐opioid agonists on neural activity of Sst‐GABA DMV neurons because their in vivo administration in the DMV mimics GABA blockade in the nucleus. Experiments were conducted in brain slice preparation of transgenic adult Sst‐IRES‐Cre mice expressing tdTomato fluorescence, channelrhodopsin‐2, archaerhodopsin or GCaMP3. Electrophysiological recordings were obtained from Sst‐GABA DMV neurons or DiI labelled gastric‐antrum projecting DMV neurons. Our results show that optogenetic stimulation of Sst‐GABA neurons results in a robust inhibition of action potentials of labelled premotor DMV neurons to the gastric‐antrum through an increase in inhibitory post‐synaptic currents. The activity of the Sst‐GABA neurons in the DMV is inhibited by both melanocortin and μ‐opioid agonists. These agonists counteract the

  9. The role of water intake on cardiac vagal reactivation after upper-body resistance exercise.

    PubMed

    Teixeira, A L; Ramos, P S; Marins, J B; Ricardo, D R

    2015-03-01

    The aim of this study was to assess the hypothesis that water intake will accelerate cardiac vagal reactivation after a single session of upper-body resistance exercise. 13 healthy men (26.5±5.9 years) with previous experience in resistance training were enrolled. In visits 1 and 2, participants performed the one-repetition maximum (1RM) test and retest with the bench press exercise. The sessions 3 and 4 were performed randomly, while participants consumed 500 ml (experimental visit) or 50 ml (control visit) of water immediately after 3 sets of maximum repetitions at 80% of 1RM. Cardiac vagal activity was represented by cardiac vagal index (CVI) measured before, immediately after and 30 min post-exercise. Additionally, heart rate and blood pressure were measured. The results show that CVI was higher 30 min post-exercise when 500 ml of water was ingested compared to 50 ml (1.39±0.07 vs. 1.23±0.07; p=0.02) (mean±SEM). Heart rate and blood pressure values were similar in both trials. We conclude that water intake accelerates post-resistance exercise cardiac vagal reactivation. These findings suggest that hydration after resistance exercise might be beneficial for cardiovascular safety in healthy subjects. © Georg Thieme Verlag KG Stuttgart · New York.

  10. MEAL PARAMETERS AND VAGAL GASTROINTESTINAL AFFERENTS IN MICE THAT EXPERIENCED EARLY POSTNATAL OVERNUTRITION

    PubMed Central

    Biddinger, Jessica E.; Fox, Edward A.

    2010-01-01

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component - the vagus nerve - has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal-size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 hour/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. PMID:20403369

  11. Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

    PubMed

    Lunding, J A; Nordström, L M; Haukelid, A-O; Gilja, O H; Berstad, A; Hausken, T

    2008-06-01

    Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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.

  14. Dorsal motor nucleus of the vagus neurons: a multivariate taxonomy.

    PubMed

    Jarvinen, M K; Powley, T L

    1999-01-18

    The dorsal motor nucleus of the vagus (DMNX) contains neurons with different projections and discrete functions, but little success has been achieved in distinguishing the cells cytoarchitectonically. The present experiment employed multivariate analytical techniques to evaluate DMNX neuronal morphology. Male Sprague-Dawley rats (n = 77) were perfused, and the brainstems were stained en bloc with a Golgi-Cox protocol. DMNX neurons in each of three planes (coronal, sagittal, and horizontal; total sample = 607) were digitized. Three-dimensional features quantified included dendritic length, number of segments, spine density, number of primary dendrites, dendritic orientation, and soma form factor. Cluster analyses of six independent samples of 100+ neurons and of three composite replicate pools of 200+ neurons consistently identified similar sets of four distinct neuronal profiles. One profile (spinous, limited dendrites, small somata) appears to correspond to the interneuron population of the DMNX. In contrast, the other three distinctive profiles (e.g., one is multipolar, with large dendritic fields and large somata) are different types of preganglionic neurons. Each of the four types of neurons is found throughout the DMNX, suggesting that the individual columnar subnuclei and other postulated vagal motorneuron pools are composed of all types of neurons. Within individual motor pools, ensembles of the different neuronal types must cooperatively organize different functions and project to different effectors within a target organ. By extension, specializations of the preganglionic motor pools are more likely to result from their afferent inputs, peripheral target tissues, neurochemistry, or physiological features rather than from any unique morphological profiles.

  15. Presynaptic modulation of tonic and respiratory inputs to cardiovagal motoneurons by substance P.

    PubMed

    Hou, Lili; Tang, Hongtai; Chen, Yonghua; Wang, Lin; Zhou, Xujiao; Rong, Weifang; Wang, Jijiang

    2009-08-11

    Substance P (SP) has been implicated in vagal control of heart rate and cardiac functions, but the mechanisms of SP actions on cardiac vagal activity remain obscure. The present study has investigated the effects of SP on the synaptic inputs of preganglionic cardiovagal motoneurons (CVNs) in brainstem slices of neonatal rat. Whole-cell voltage-clamp recordings were performed on retrogradely labeled CVNs in the nucleus ambiguus. The results show that in thin slices (400 microm thickness) without respiratory-like rhythm, globally applied SP (1 microM) significantly enhanced both the GABAergic and the glycinergic inputs, but had no effect on the glutamatergic inputs, of CVNs. Since inspiratory-related augmentation of the inhibitory inputs of CVNs in individual respiratory cycles is known to play an important role in the genesis of respiratory sinus arrhythmia, the effects of SP on the inhibitory inputs of CVNs were further examined in thick slices (500-800 microm thickness) with respiratory-like rhythm, and SP (1 microM) was focally applied to the CVNs under patch-clamp recording. Focally applied SP caused frequency increases of the GABAergic and the glycinergic inputs both during inspiratory bursts and during inspiratory intervals. However, the inspiratory-related augmentation of the GABAergic and the glycinergic inputs of CVNs, measured by the frequency increases during inspiratory bursts in percentage of the frequency during inspiratory intervals, was significantly decreased by SP. These results suggest that SP inhibits CVNs via enhancement of their inhibitory synaptic inputs, and SP diminishes the respiratory-related fluctuation of cardiac vagal activity in individual respiratory cycles. These results also indicate that SP may play a role in altering the vagal control of the heart in some cardiovascular diseases such as myocardial ischemia and hypertension, since these diseases are characterized by weakened cardiac vagal tone and heart rate variability, and have

  16. Vagal and sympathetic activity in burnouts during a mentally demanding workday.

    PubMed

    Zanstra, Ydwine J; Schellekens, Jan M H; Schaap, Cas; Kooistra, Libbe

    2006-01-01

    We study differences in task performance and related sympathetic-vagal reaction patterns between burnouts and controls during a mentally demanding workday. Thirty-nine adults with burnout and 40 healthy controls performed mental tasks during a simulated workday. At pretest, just before lunch (lunch test) and at the end of the day (posttest), a Stroop color word task was administered as a probe task. Efficiency (the relation between performance and effort during the probe task), performance (reaction time and errors), and effort (self-report) were measured, as well as cardiovascular indices of sympathetic (blood pressure) and vagal (respiratory sinus arrhythmia) activity. Performance and effort investment of both burnouts and controls did not differ during pretest. As the day progressed the performance of controls improved more than the performance of burnouts. Moreover, the control group showed a decrease of blood pressure in response to mental task demands, a decrease in respiratory sinus arrhythmia activity, and no change in experienced effort. In the burnout group, no change could be demonstrated in blood pressure, suggesting a sympathetic predominance in the sympathetic-vagal balance. Burnouts experienced an increase in effort and were more tired at the end of the workday. Burnouts and healthy controls differ in their pattern of sympathetic-vagal activity only after long-lasting work demands. Findings give limited support to Porges's view that in healthy subjects, the vagal system is more responsive to challenging task situations than in chronically stressed individuals. The distinction between two phases in the burnout on the basis of behavioral and physiological characteristics is discussed.

  17. Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors.

    PubMed

    Darling, Rebecca A; Zhao, Huan; Kinch, Dallas; Li, Ai-Jun; Simasko, Steven M; Ritter, Sue

    2014-07-01

    β-mercaptoacetate (MA) is a drug known to block mitochondrial oxidation of medium- and long-chain fatty acids (FAs) and to stimulate feeding. Because MA-induced feeding is vagally dependent, it has been assumed that the feeding response is mediated by MA's antimetabolic action at a peripheral, vagally innervated site. However, MA's site of action has not yet been identified. Therefore, we used fluorescent calcium measurements in isolated neurons from rat nodose ganglia to determine whether MA has direct effects on vagal sensory neurons. We found that MA alone did not alter cytosolic calcium concentrations in nodose neurons. However, MA (60 μM to 6 mM) significantly decreased calcium responses to both linoleic acid (LA; 10 μM) and caprylic acid (C8; 10 μM) in all neurons responsive to LA and C8. GW9508 (40 μM), an agonist of the FA receptor, G protein-coupled receptor 40 (GPR40), also increased calcium levels almost exclusively in FA-responsive neurons. MA significantly inhibited this response to GW9508. MA did not inhibit calcium responses to serotonin, high K(+), or capsaicin, which do not utilize GPRs, or to CCK, which acts on a different GPR. GPR40 was detected in nodose ganglia by RT-PCR. Results suggest that FAs directly activate vagal sensory neurons via GPR40 and that MA antagonizes this effect. Thus, we propose that MA's nonmetabolic actions on GPR40 membrane receptors, expressed by multiple peripheral tissues in addition to the vagus nerve, may contribute to or mediate MA-induced stimulation of feeding. Copyright © 2014 the American Physiological Society.

  18. Effect of vagal stimulation on gastric mucosal barrier in albino rats.

    PubMed

    Somasundaram, K; Ganguly, A K

    1987-01-01

    To study the influence of vagus nerves on gastric mucosal barrier in albino rats, gastric adherent mucus and mucosal epithelial neutral glycoproteins were quantitatively assessed after vagal stimulation at the cardio-esophageal region by a specially designed circular electrode. Gastric adherent mucus and epithelial mucus were studied from oxyntic and pyloric gland areas by Alcian blue binding and periodic acid Schiff's (PAS) staining method respectively. The results when compared with sham operated control animals showed increase in the visible mucus concurrent with decrease in PAS positive materials. The stimulation at the cardio-esophageal region of vagotomized animals did not produce these effects. This study indicates that in an acute condition, increased vagal influence is important in increasing mucus secretion and strengthening the first line of defence of the mucosal barrier.

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

    PubMed

    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.

  20. Cardiac vagal tone is correlated with selective attention to neutral distractors under load.

    PubMed

    Park, Gewnhi; Vasey, Michael W; Van Bavel, Jay J; Thayer, Julian F

    2013-04-01

    We examined whether cardiac vagal tone (indexed by heart rate variability, HRV) was associated with the functioning of selective attention under load. Participants were instructed to detect a target letter among letter strings superimposed on either fearful or neutral distractor faces. Under low load, when letter strings consisted of six target letters, there was no difference between people with high and low HRV on task performance. Under high load, when letter strings consisted of one target letter and five nontarget letters, people with high HRV were faster in trials with neutral distractors, but not with fearful distractors. However, people with low HRV were slower in trials with both fearful and neutral distractors. The current research suggests cardiac vagal tone is associated with successful control of selective attention critical for goal-directed behavior, and its impact is greater when fewer cognitive resources are available. Copyright © 2013 Society for Psychophysiological Research.

  1. Resection of cervical vagal schwannoma via a post-auricular approach.

    PubMed

    Roh, Jong-Lyel

    2006-03-01

    Cervical vagal schwannomas are extremely rare and gross total resection is the standard treatment modality. However, because the conventional cervical approach leaves an incision scar in a visible area, other approaches need to be developed for young women who want the postoperative scar to be invisible. A 28-year-old female underwent complete resection of a 4x4 cm tumor in her right upper neck via a post-auricular approach using an inverted V-shaped incision along the post-auricular sulcus and hairline. The tumor was a schwannoma originating from the right cervical vagus nerve. Postoperatively, right vocal cord paralysis developed despite careful dissection but completely recovered within 6 months after surgery. The patient was satisfied with an invisible external scar which was hidden by her auricle and hair. A cervical vagal schwannoma can be successfully removed by making an incision in a potentially invisible area.

  2. Intraoperative monitoring of the recurrent laryngeal nerve by vagal nerve stimulation in thyroid surgery.

    PubMed

    Farizon, Brigitte; Gavid, Marie; Karkas, Alexandre; Dumollard, Jean-Marc; Peoc'h, Michel; Prades, Jean-Michel

    2017-01-01

    The aim of the present study was to evaluate the thyroarytenoid muscle response during bilateral thyroid surgery using vagal nerve stimulation. 195 patients (390 nerves at risk) underwent a total thyroidectomy. The recurrent laryngeal nerve's function was checked by analyzing the amplitude and the latency of the thyroarytenoid muscle's responses after a vagal nerve's stimulation (0.5 and 1 mA) using the NIM3 Medtronic system. All patients were submitted to preoperative and postoperative laryngoscopy. 20 patients get no thyroarytenoid muscle response to the vagal nerve stimulation, and 14 postoperative recurrent laryngeal nerve palsies were confirmed (3.8 %). Two palsies were present after 6 months (0.51 %). All the patients with muscle's response have normal mobility vocal fold. The test sensitivity was 100 % and the test specificity was 98 %. Physiologically, the mean latencies of the muscular potentials for the right RLN were, respectively, 3.89 and 3.83 ms (p > 0.05) for the stimulation at 0.5 and 1 mA. The mean latencies for the left RLN were, respectively, 6.25 and 6.22 ms for the stimulation at 0.5 and 1 mA (p > 0.05). The difference of the latencies between the right and the left nerve was 2.30 ms (1.75-3.25 ms) with a stimulation of 0.5 or 1 mA (p < 0.05). Thyroarytenoid muscle's response via a vagal nerve stimulation showed a functional asymmetry of the laryngeal adduction with a faster right response. Surgically, this method can predict accurately an immediate postoperative vocal folds function in patients undergoing a bilateral thyroid surgery.

  3. Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors

    PubMed Central

    Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

    2006-01-01

    Glutamate acts at central synapses via ionotropic (iGluR – NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed. PMID:16945965

  4. Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors.

    PubMed

    Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

    2006-11-15

    Glutamate acts at central synapses via ionotropic (iGluR--NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed.

  5. Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

    PubMed

    Biddinger, Jessica E; Fox, Edward A

    2010-08-04

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Dietary fibers solubilized in water or an oil emulsion induce satiation through CCK-mediated vagal signaling in mice.

    PubMed

    Rasoamanana, Rojo; Chaumontet, Catherine; Nadkarni, Nachiket; Tomé, Daniel; Fromentin, Gilles; Darcel, Nicolas

    2012-11-01

    This study focused on the fate of the satiating potency of dietary fibers when solubilized in a fat-containing medium. Fourteen percent of either guar gum (GG) or fructo-oligosaccharide (FOS) or a mixture of the 2 (GG-FOS, 5% GG and 9% FOS) were solubilized in water or an oil emulsion (18-21% rapeseed oil in water, v:v) and administered by gavage to mice before their food intake was monitored. When compared with water (control), only GG-FOS solubilized in water or in the oil emulsion reduced daily energy intake by 21.1 and 14.1%, respectively. To further describe this effect, the meal pattern was characterized and showed that GG-FOS increased satiation without affecting satiety by diminishing the size and duration of meals for up to 9 h after administration independently of the solubilization medium. The peripheral blockade of gut peptide receptors showed that these effects were dependent on the peripheral signaling of cholecystokinin but not of glucagon-like peptide 1, suggesting that anorectic signals emerge from the upper intestine rather than from distal segments. Measurements of neuronal activation in the nucleus of solitary tract supported the hypothesis of vagal satiation signaling because a 3-fold increase in c-Fos protein expression was observed in that nucleus after the administration of GG-FOS, independently of the solubilization medium. Taken together, these data suggest that a mixture of GG and FOS can maintain its appetite suppressant effect in fatty media. Adding these dietary fibers to fat-containing foods might therefore be useful in managing food intake.

  7. Lymphocyte responses to stress in postpartum women: relationship to vagal tone.

    PubMed

    Redwine, L S; Altemus, M; Leong, Y M; Carter, C S

    2001-04-01

    Although women spend their lives in various phases of the reproductive cycle, including menstrual, pregnancy, postpartum, lactation and menopause, few studies have examined immune responses to stress in women as a function of events associated with reproduction. The objective of this study was to evaluate differential effects of breastfeeding (n = 16), bottlefeeding (n = 10) and non-postpartum (n = 10) status on lymphocyte responses to stressful tasks (public speaking and mental arithmetic). To measure cellular immune responses, lymphocyte proliferation to plant lectins, poke weed mitogen (PWM) and phytohemagglutinin (PHA) were used. The autonomic measures, heart rate, vagal tone, blood pressure and the hormones of the HPA axis, ACTH and cortisol, were measured and their possible roles in mediating lymphocyte proliferation responses were examined. Recently parturient women who were breastfeeding or bottlefeeding had attenuated stress-induced change in lymphocyte responses to PWM compared with non-postpartum women, tested in the follicular phase of their cycle (P < 0.05). Also, lymphocyte responses to PHA were higher in the breastfeeding group compared with non-postpartum controls (P < 0.05). Regression analyses revealed that an index of cardiac vagal tone, but not other autonomic or endocrine measures, was positively predictive of lymphocyte proliferation to PWM. To summarize, these findings suggest that lactation and parturition can influence lymphocyte proliferation and that activity in the vagal system may influence lymphocyte responses to stress.

  8. Peripheral functional organisation of vagally evoked gastric motor responses in the ferret.

    PubMed Central

    Andrews, P L; Lawes, I N; Bower, A J

    1980-01-01

    The aims of the present study were to determine the relative amplitudes of intragastric motor responses evoked by different vagal branches and to establish whether the effects of acute or chronic vagotomy could be predicted from these data. Intragastric pressure responses to electrical stimulation of the vagus were measured in urethane-anaesthetised ferrets and acute or chronic vagotomies were performed. The results show that the left and right cervical vagi were equipotential and fully overlaped each other. Their contributions to the dorsal trunk were equipotential and fully overlapping and so were their contributions to the ventral trunk. The dorsal trunk was more effective than the ventral trunk and there was total functional overlap between these two trunks. Vagal evoked gastric motor responses of the ferret are apparently organised in a different way from vagally induced acid secretion or hormone release in the cat. Acute removal of a trunk led to a reduction in evoked responses that was not linear function of the effect of stimulation of that trunk. In contrast, chronic removal caused a relative increase in evoked responses that ws inversely related to the decrease caused by acute removal. The implications of total functional overlap and neuromuscular reorganisation after chronic vagotomy are discussed. PMID:7439800

  9. Learning by heart-the relationship between resting vagal tone and metacognitive judgments: a pilot study.

    PubMed

    Meessen, Judith; Sütterlin, Stefan; Gauggel, Siegfried; Forkmann, Thomas

    2018-05-23

    Metacognitive awareness and resting vagally mediated heart rate variability (HRV) as a physiological trait marker of cognitive inhibitory control capacities are both associated with better well-being and seem to share a common neural basis. Executive functioning which is considered a prerequisite for delivering prospective metacognitive judgments has been found to be correlated with HRV. This pilot study addresses the question, whether metacognitive awareness and resting vagally mediated HRV are positively associated. A sample of 20 healthy participants was analyzed that completed a typical Judgment of Learning task after an electrocardiogram had been recorded. The root-mean-squares of successive differences were used to calculate vagally mediated HRV. Metacognitive awareness was measured by comparing the judgments of learning with the actual memory performance, yielding a deviation score. HRV was found to be positively correlated with metacognitive awareness. Results suggest that metacognitive abilities might relate to physiological trait markers of cognitive inhibitory control capacities. Further experimental studies are needed to investigate causal relations.

  10. Roles for gut vagal sensory signals in determining energy availability and energy expenditure.

    PubMed

    Schwartz, Gary J

    2018-08-15

    The gut sensory vagus transmits a wide range of meal-related mechanical, chemical and gut peptide signals from gastrointestinal and hepatic tissues to the central nervous system at the level of the caudal brainstem. Results from studies using neurophysiological, behavioral physiological and metabolic approaches that challenge the integrity of this gut-brain axis support an important role for these gut signals in the negative feedback control of energy availability by limiting food intake during a meal. These experimental approaches have now been applied to identify important and unanticipated contributions of the vagal sensory gut-brain axis to the control of two additional effectors of overall energy balance: the feedback control of endogenous energy availability through hepatic glucose production and metabolism, and the control of energy expenditure through brown adipose tissue thermogenesis. Taken together, these studies reveal the pleiotropic influences of gut vagal meal-related signals on energy balance, and encourage experimental efforts aimed at understanding how the brainstem represents, organizes and coordinates gut vagal sensory signals with these three determinants of energy homeostasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

    NASA Technical Reports Server (NTRS)

    Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

    2001-01-01

    Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

  12. Sex differences in the associations between vagal reactivity and oppositional defiant disorder symptoms.

    PubMed

    Vidal-Ribas, Pablo; Pickles, Andrew; Tibu, Florin; Sharp, Helen; Hill, Jonathan

    2017-09-01

    Vagal reactivity to stress in children has been associated with future psychiatric outcomes. However, results have been mixed possibly because these effects are in opposite direction in boys and girls. These sex differences are relevant in the context of development of psychopathology, whereby the rates of psychiatric disorders differ by sex. In this study, we aimed to examine the association between vagal reactivity, assessed as a reduction in respiratory sinus arrhythmia (RSA) in response to a challenge, and the development of future oppositional defiant disorder (ODD) symptoms in boys and girls. In addition, we examine the specific associations with ODD symptom dimensions, named irritability and headstrong. We hypothesized that increased vagal reactivity was associated with increased ODD symptoms in girls and a reduction in ODD symptoms in boys. Participants were members of the Wirral Child Health and Development Study, a prospective epidemiological longitudinal study of 1,233 first-time mothers recruited at 20 weeks' gestation. RSA during four nonstressful and one stressful (still-face) procedures was assessed when children were aged 29 weeks in a sample stratified by adversity (n = 270). Maternal reports of ODD symptoms were collected when children were 2.5 years old (n = 253), 3.5 years old (n = 826), and 5 years old (n = 770). Structural equation modeling (SEM) was employed to test our hypotheses. There was a significant sex difference in the prediction of ODD symptoms due to the opposite directionality in which increasing vagal reactivity was associated with an increase in ODD symptoms in girls and a reduction of ODD symptoms in boys. This Sex by Vagal reactivity interaction was common for both ODD dimensions, with no sex by dimension-specific associations. Physiological reactivity to a stressful situation predicts differently ODD symptoms in boys and girls very early in life, with no difference across irritability and headstrong components

  13. The influence of vagal control on sex-related differences in left ventricular mechanics and hemodynamics.

    PubMed

    Williams, Alexandra Mackenzie; Shave, Robert E; Coulson, James M; White, Harriet; Rosser-Stanford, Bryn; Eves, Neil Derek

    2018-06-01

    Left ventricular (LV) twist mechanics differ between males and females during acute physiological stress, which may be partly mediated by sex differences in autonomic control. While males appear to have greater adrenergic control of LV twist, the potential contribution of vagal modulation to sex differences in LV twist remains unknown. Therefore, this study examined the role of vagal control on sex differences in LV twist during graded lower body negative pressure (LBNP) and supine cycling. On two separate visits, LV mechanics were assessed using 2-dimensional speckle-tracking echocardiography in 18 males (22{plus minus}2yr) and 17 females (21{plus minus}4yr) during -40 and -60 mmHg LBNP and 25% and 50% of peak supine cycling workload, with and without glycopyrrolate (vagal blockade). LV twist was not different at baseline but was greater in females during -60 mmHg in both control (F:16.0{plus minus}3.4º, M:12.9{plus minus}2.3º, p=0.004) and glycopyrrolate trials (F:17.7{plus minus}5.9{degree sign}, M:13.9{plus minus}3.3{degree sign}, p<0.001) due to greater apical rotation during control (F:11.9{plus minus}3.6º, M:7.8{plus minus}1.5º, p<0.001) and glycopyrrolate (F:11.6{plus minus}4.9{degree sign}, M:7.1{plus minus}3.6{degree sign}, p=0.009). These sex differences in LV twist consistently coincided with a greater LV sphericity index (i.e. ellipsoid geometry) in females compared to males. In contrast, LV twist did not differ between the sexes during exercise, with or without glycopyrrolate. Females have augmented LV twist compared to males during large reductions to preload, even during vagal blockade. As such, differences in vagal control do not appear to contribute to sex differences in the LV twist responses to physiological stress, but may be related to differences in ventricular geometry.

  14. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation

    PubMed Central

    Cork, Simon C.

    2015-01-01

    Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation. PMID:26290108

  15. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.

    PubMed

    Trapp, Stefan; Cork, Simon C

    2015-10-15

    Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation. Copyright © 2015 the American Physiological Society.

  16. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

    PubMed

    Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

    2014-01-01

    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.

  17. Mothers’ Responses to Children’s Negative Emotions and Child Emotion Regulation: The Moderating Role of Vagal Suppression

    PubMed Central

    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

  18. A novel subset of enteric neurons revealed by ptf1a:GFP in the developing zebrafish enteric nervous system.

    PubMed

    Uribe, Rosa A; Gu, Tiffany; Bronner, Marianne E

    2016-03-01

    The enteric nervous system, the largest division of the peripheral nervous system, is derived from vagal neural crest cells that invade and populate the entire length of the gut to form diverse neuronal subtypes. Here, we identify a novel population of neurons within the enteric nervous system of zebrafish larvae that express the transgenic marker ptf1a:GFP within the midgut. Genetic lineage analysis reveals that enteric ptf1a:GFP(+) cells are derived from the neural crest and that most ptf1a:GFP(+) neurons express the neurotransmitter 5HT, demonstrating that they are serotonergic. This transgenic line, Tg(ptf1a:GFP), provides a novel neuronal marker for a subpopulation of neurons within the enteric nervous system, and highlights the possibility that Ptf1a may act as an important transcription factor for enteric neuron development. © 2016 Wiley Periodicals, Inc.

  19. Electroacupuncture improves burn-induced impairment in gastric motility mediated via the vagal mechanism in rats.

    PubMed

    Song, J; Yin, J; Sallam, H S; Bai, T; Chen, Y; Chen, J D Z

    2013-10-01

    Delayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns. Male rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24 h post severe burns. (i) Burn delayed GE (P < 0.001). Electroacupuncture improved GE 6 and 24 h post burn (P < 0.001). Vagotomy blocked the EA effect on GE. (ii) Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24 h post burn (P = 0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P = 0.004) and 24 h post burn (P = 0.03, vs sham-EA). (iv) Electroacupuncture attenuated burn-induced increase in plasma IL-6 at both 6 (P = 0.03) and 24 h post burn (P = 0.003). Electroacupuncture at ST-36 improves gastric dysrhythmia and accelerates GE in rats with burns. The improvement seems to be mediated via the vagal pathway involving the inflammatory cytokine IL-6. © 2013 John Wiley & Sons Ltd.

  20. Effects of acute exercise on attenuated vagal baroreflex function during bed rest

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.; Doerr, Donald F.; Guell, Antonio; Marini, J.-F.

    1992-01-01

    We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 deg head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally-mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4 percent (p less than 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p less than 0.05) by 10.7 +/- 3.7 percent above pre-bed rest levels and 34.3 +/- 7.9 percent above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise.

  1. Altered cardiovascular vagal responses in nonelderly female patients with subclinical hyperthyroidism and no apparent cardiovascular disease.

    PubMed

    Portella, Renata Boschi; Pedrosa, Roberto Coury; Coeli, Claudia Medina; Buescu, Alexandru; Vaisman, Mario

    2007-08-01

    Subclinical hyperthyroidism (SH) has been associated with exercise intolerance, changes in cardiac morphology, atrial arrhythmias and sympathovagal imbalance. The aim of this study was to evaluate the vagal reserve and modulation by a sympathetic stimulus in nonelderly patients with SH without cardiovascular problems. We carried out a cross-sectional study, comparing data of the heart rate variability (HRV) of SH patients and healthy controls at rest and after vagal and sympathetic stimulation. We studied 16 female patients with at least 6 months of SH and 16 healthy female controls with the same median age (40 vs. 34.5 years). We used the tilt test, with electrocardiographic record at rest, during the respiratory sinus arrhythmia (RSA) manoeuvre and after tilting, in order to analyse HRV in the frequency domain (%high frequency (HF) and low/high frequency ratio (LF/HF) using Biopotentials Captation System software. The median TSH level was 0.03 mU/l in patients and 1.37 mUI/l in controls. The median free T4 was 1.37 ng/dl in patients and 1.20 ng/dl in controls. Patients demonstrated a significantly smaller difference between %HF during the RSA and %HF at rest than controls (median -7.5 vs. 36.6, P < 0.001). There was a lower difference between LF/HF ratio after tilting and LF/HF ratio at rest in patients than in controls (1.5 vs. 5.3, P = 0.005). Subclinical hyperthyroidism affects cardiovascular autonomic balance in otherwise apparently healthy nonelderly females by blunting vagal responses.

  2. Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

    PubMed

    Zhang, Youhua; Popović, Zoran B; Kusunose, Kenya; Mazgalev, Todor N

    2013-01-01

    Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF. © 2012 Wiley Periodicals, Inc.

  3. Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

    NASA Technical Reports Server (NTRS)

    Cox, James F.; Tahvanainen, Kari U O.; Kuusela, Tom A.; Levine, Benjamin D.; Cooke, William H.; Mano, Tadaaki; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Ertl, Andrew C.; hide

    2002-01-01

    When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

  4. Vagal-dependent nonlinear variability in the respiratory pattern of anesthetized, spontaneously breathing rats

    PubMed Central

    Dhingra, R. R.; Jacono, F. J.; Fishman, M.; Loparo, K. A.; Rybak, I. A.

    2011-01-01

    Physiological rhythms, including respiration, exhibit endogenous variability associated with health, and deviations from this are associated with disease. Specific changes in the linear and nonlinear sources of breathing variability have not been investigated. In this study, we used information theory-based techniques, combined with surrogate data testing, to quantify and characterize the vagal-dependent nonlinear pattern variability in urethane-anesthetized, spontaneously breathing adult rats. Surrogate data sets preserved the amplitude distribution and linear correlations of the original data set, but nonlinear correlation structure in the data was removed. Differences in mutual information and sample entropy between original and surrogate data sets indicated the presence of deterministic nonlinear or stochastic non-Gaussian variability. With vagi intact (n = 11), the respiratory cycle exhibited significant nonlinear behavior in templates of points separated by time delays ranging from one sample to one cycle length. After vagotomy (n = 6), even though nonlinear variability was reduced significantly, nonlinear properties were still evident at various time delays. Nonlinear deterministic variability did not change further after subsequent bilateral microinjection of MK-801, an N-methyl-d-aspartate receptor antagonist, in the Kölliker-Fuse nuclei. Reversing the sequence (n = 5), blocking N-methyl-d-aspartate receptors bilaterally in the dorsolateral pons significantly decreased nonlinear variability in the respiratory pattern, even with the vagi intact, and subsequent vagotomy did not change nonlinear variability. Thus both vagal and dorsolateral pontine influences contribute to nonlinear respiratory pattern variability. Furthermore, breathing dynamics of the intact system are mutually dependent on vagal and pontine sources of nonlinear complexity. Understanding the structure and modulation of variability provides insight into disease effects on respiratory

  5. Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats.

    PubMed

    Mizuno, Masaki; Kawada, Toru; Kamiya, Atsunori; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Smith, Scott A; Sugimachi, Masaru

    2011-04-01

    We examined the transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained (16 wk, treadmill for 1 h, 5 times/wk at 15 m/min and 15-degree grade) rats for comparison to HR variability assessed in the conscious resting state. The transfer function from sympathetic stimulation to HR response was similar between groups (gain, 4.2 ± 1.5 vs. 4.5 ± 1.5 beats·min(-1)·Hz(-1); natural frequency, 0.07 ± 0.01 vs. 0.08 ± 0.01 Hz; damping coefficient, 1.96 ± 0.55 vs. 1.69 ± 0.15; and lag time, 0.7 ± 0.1 vs. 0.6 ± 0.1 s; sedentary vs. exercise trained, respectively, means ± SD). The transfer gain from vagal stimulation to HR response was 6.1 ± 3.0 in the sedentary and 9.7 ± 5.1 beats·min(-1)·Hz(-1) in the exercise-trained group (P = 0.06). The corner frequency (0.11 ± 0.05 vs. 0.17 ± 0.09 Hz) and lag time (0.1 ± 0.1 vs. 0.2 ± 0.1 s) did not differ between groups. When the sympathetic transfer gain was averaged for very-low-frequency and low-frequency bands, no significant group effect was observed. In contrast, when the vagal transfer gain was averaged for very-low-frequency, low-frequency, and high-frequency bands, exercise training produced a significant group effect (P < 0.05 by two-way, repeated-measures ANOVA). These findings suggest that, in the frequency domain, exercise training augments the dynamic HR response to vagal stimulation but not sympathetic stimulation, regardless of the frequency bands.

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

    PubMed Central

    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

  7. Differential regulation of ASICs and TRPV1 by zinc in rat bronchopulmonary sensory neurons.

    PubMed

    Vysotskaya, Zhanna V; Moss, Charles R; Gu, Qihai

    2014-12-01

    Zinc has been known to act as a signaling molecule that regulates a variety of neuronal functions. In this study, we aimed to study the effect of zinc on two populations of acid-sensitive ion channels, acid-sensing ion channels (ASICs), and transient receptor potential vanilloid receptor-1 (TRPV1), in vagal bronchopulmonary sensory neurons. Rat vagal sensory neurons innervating lungs and airways were retrogradely labeled with a fluorescent tracer. Whole-cell perforated patch-clamp recordings were carried out in primarily cultured bronchopulmonary sensory neurons. The acid-evoked ASIC and TRPV1 currents were measured and compared between before and after the zinc pretreatment. ASIC currents were induced by a pH drop from 7.4 to 6.8 or 6.5 in the presence of capsazepine (10 µM), a specific TRPV1 antagonist. Pretreatment with zinc (50 or 300 µM, 2 min) displayed different effects on the two distinct phenotypes of ASIC currents: a marked potentiation on ASIC channels with fast kinetics of activation and inactivation or no significant effect on ASIC currents with slow activation and inactivation. On the other hand, pretreatment with zinc significantly inhibited the acid (pH 5.5 or 5.3)-induced TRPV1 currents. The inhibition was abolished by intracellular chelation of zinc by TPEN (25 µM), indicating that intracellular accumulation of zinc was likely required for its inhibitory effect on TRPV1 channels. Our study showed that zinc differentially regulates the activities of ASICs and TRPV1 channels in rat vagal bronchopulmonary sensory neurons.

  8. An approach to contouring the dorsal vagal complex for radiotherapy planning

    SciT

    O'Steen, Lillie; Amdur, Robert J., E-mail: amdurr@shands.ufl.edu

    Multiple studies suggest that radiation dose to the area of the brainstem called the “dorsal vagal complex (DVC)” influences the frequency of nausea and vomiting during radiotherapy. The purpose of this didactic article is to describe the step-by-step process that we use to contour the general area of the DVC on axial computed tomography (CT) images as would be done for radiotherapy planning. The contouring procedure that we describe for contouring the area of the DVC is useful to medical dosimetrists and radiation oncologists.

  9. A model-based approach for the evaluation of vagal and sympathetic activities in a newborn lamb.

    PubMed

    Le Rolle, Virginie; Ojeda, David; Beuchée, Alain; Praud, Jean-Paul; Pladys, Patrick; Hernández, Alfredo I

    2013-01-01

    This paper proposes a baroreflex model and a recursive identification method to estimate the time-varying vagal and sympathetic contributions to heart rate variability during autonomic maneuvers. The baroreflex model includes baroreceptors, cardiovascular control center, parasympathetic and sympathetic pathways. The gains of the global afferent sympathetic and vagal pathways are identified recursively. The method has been validated on data from newborn lambs, which have been acquired during the application of an autonomic maneuver, without medication and under beta-blockers. Results show a close match between experimental and simulated signals under both conditions. The vagal and sympathetic contributions have been simulated and, as expected, it is possible to observe different baroreflex responses under beta-blockers compared to baseline conditions.

  10. The Role of Baseline Vagal Tone in Dealing with a Stressor during Face to Face and Computer-Based Social Interactions.

    PubMed

    Rigoni, Daniele; Morganti, Francesca; Braibanti, Paride

    2017-01-01

    Facing a stressor involves a cardiac vagal tone response and a feedback effect produced by social interaction in visceral regulation. This study evaluated the contribution of baseline vagal tone and of social engagement system (SES) functioning on the ability to deal with a stressor. Participants ( n = 70) were grouped into a minimized social interaction condition (procedure administered through a PC) and a social interaction condition (procedure administered by an experimenter). The State Trait Anxiety Inventory, the Social Interaction Anxiety Scale, the Emotion Regulation Questionnaire and a debriefing questionnaire were completed by the subjects. The baseline vagal tone was registered during the baseline, stressor and recovery phases. The collected results highlighted a significant effect of the baseline vagal tone on vagal suppression. No effect of minimized vs. social interaction conditions on cardiac vagal tone during stressor and recovery phases was detected. Cardiac vagal tone and the results of the questionnaires appear to be not correlated. The study highlighted the main role of baseline vagal tone on visceral regulation. Some remarks on SES to be deepen in further research were raised.

  11. The Role of Baseline Vagal Tone in Dealing with a Stressor during Face to Face and Computer-Based Social Interactions

    PubMed Central

    Rigoni, Daniele; Morganti, Francesca; Braibanti, Paride

    2017-01-01

    Facing a stressor involves a cardiac vagal tone response and a feedback effect produced by social interaction in visceral regulation. This study evaluated the contribution of baseline vagal tone and of social engagement system (SES) functioning on the ability to deal with a stressor. Participants (n = 70) were grouped into a minimized social interaction condition (procedure administered through a PC) and a social interaction condition (procedure administered by an experimenter). The State Trait Anxiety Inventory, the Social Interaction Anxiety Scale, the Emotion Regulation Questionnaire and a debriefing questionnaire were completed by the subjects. The baseline vagal tone was registered during the baseline, stressor and recovery phases. The collected results highlighted a significant effect of the baseline vagal tone on vagal suppression. No effect of minimized vs. social interaction conditions on cardiac vagal tone during stressor and recovery phases was detected. Cardiac vagal tone and the results of the questionnaires appear to be not correlated. The study highlighted the main role of baseline vagal tone on visceral regulation. Some remarks on SES to be deepen in further research were raised. PMID:29234291

  12. Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

    PubMed

    Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

    2018-04-01

    Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Less Empathic and More Reactive: The Different Impact of Childhood Maltreatment on Facial Mimicry and Vagal Regulation

    PubMed Central

    Ardizzi, Martina; Umiltà, Maria Alessandra; Evangelista, Valentina; Di Liscia, Alessandra; Ravera, Roberto; Gallese, Vittorio

    2016-01-01

    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 others

  14. Similarities of the neuronal circuit for the induction of fictive vomiting between ferrets and dogs.

    PubMed

    Onishi, Takako; Mori, Takashi; Yanagihara, Mamoru; Furukawa, Naohiro; Fukuda, Hiroyuki

    2007-10-30

    Previous studies suggested that the following neuronal circuit participates in the induction of vomiting by afferent vagal stimulation in decerebrated paralyzed dogs: (1) afferent fibers of the vagus nerve, (2) neurons of the solitary nucleus (NTS), (3) neurons of the prodromal sign center near the semicompact part of the nucleus ambiguus (scAMB), (4) neurons of the central pattern generator in the reticular area adjacent to the compact part of nucleus ambiguus (cAMB), (5) respiratory premotor neurons in the caudal medulla, (6) motor neurons of the diaphragm and abdominal muscles. However, the commonality of this neuronal circuit in different species has not yet been clarified. Thus, this study was conducted to clarify this point. This study clarified for the first time that fictive vomiting in decerebrated paralyzed ferrets could be induced by vagal stimulation, and could be identified by centrifugal activity patterns of the phrenic and abdominal muscle nerves. The distributions of c-Fos immunoreactive neurons in the NTS, scAMB and cAMB areas in ferrets that exhibited fictive vomiting were denser than those in ferrets that did not. Application of the nonNMDA receptor antagonist into the 4th ventricle produced the reversible suppression of fictive vomiting. The NK1 receptor immunoreactive puncta were found in the reticular area adjacent to the scAMB. Microinjections of NK1 receptor antagonist into the reticular areas on both sides abolished fictive vomiting. All these results in the ferrets are identical with results previously obtained in dogs and cats. Therefore, this suggests that the above neuronal circuit commonly participates in the induction of emesis in these animal species.

  15. Effects of eating on vection-induced motion sickness, cardiac vagal tone, and gastric myoelectric activity

    NASA Technical Reports Server (NTRS)

    Uijtdehaage, S. H.; Stern, R. M.; Koch, K. L.

    1992-01-01

    This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings.

  16. Dynamic changes in parent affect and adolescent cardiac vagal regulation: a real-time analysis.

    PubMed

    Cui, Lixian; Morris, Amanda Sheffield; Harrist, Amanda W; Larzelere, Robert E; Criss, Michael M

    2015-04-01

    The current study explored the role of parents' negative and positive affect in adolescent respiratory sinus arrhythmia (RSA) reactivity during a parent-adolescent conflict discussion task and the moderating effects of adolescent sex and age. Questionnaire data were collected from 206 adolescents (10-18 years of age; M = 13.37 years) and their primary caregivers (83.3% biological mothers). Electrocardiogram and respiration data were collected from adolescents, and RSA variables were computed. Parent affect was coded during the conflict discussion task. Multilevel modeling was used to distinguish the between- and within-individual effects of parent affect on adolescent RSA. Results indicated that observed within-parent-teen dyad anger was negatively associated with adolescent RSA, controlling for previous-minute RSA level, particularly among adolescents 13 years and older. In addition, observed between-dyad positive affect was positively linked to RSA for both boys and girls when previous-minute RSA level was controlled. Within-dyad positive affect was positively related to girl's RSA only. These findings suggest that expressions of positive affect may be related to better vagal regulation (RSA increases), whereas expressions of anger may be related to poor vagal regulation (RSA decreases) during social engagement. (c) 2015 APA, all rights reserved).

  17. Vagal Nerve Stimulator Malfunction with Change in Neck Position: Case Report and Literature Review.

    PubMed

    D'Agostino, Erin; Makler, Vyacheslav; Bauer, David F

    2018-06-01

    Vagal nerve stimulation is a safe and well-tolerated treatment for drug-resistant epilepsy. Complications and failure of the device can result from lead fracture, device malfunction, disconnection, or battery displacement and can result in a variety of symptoms. We present an interesting case of stimulator malfunction with increased impedance change seen only with a change in head position. The patient is a 25-year-old male with a vagal nerve stimulator (VNs) placed for medically refractory epilepsy who presented with neck pain and an electrical pulling sensation in his neck whenever he turned his head to the right. Initial interrogation of the VNs showed normal impedance. Subsequent interrogation with the patient's head turned found increased impedance only when the head was turned to the right. The patient had successful removal and replacement of the device with resolution of his preoperative complaints. Partial lead fracture was seen at explant. VNs malfunction can present in atypical ways. Positional maneuvers may help with its timely diagnosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome

    PubMed Central

    Beaumont, Alison; Burton, Alexander R.; Lemon, Jim; Bennett, Barbara K.; Lloyd, Andrew; Vollmer-Conna, Uté

    2012-01-01

    Background Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. Methods Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between–group differences in autonomic reactivity and associations with cognitive performance were analysed. Results Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. Conclusions These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity. PMID:23166694

  19. Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge.

    PubMed

    Schelegle, Edward S; Walby, William F

    2012-05-31

    Brown-Norway rats (n=113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O(3)) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0ppm O(3) for 8h. There were three groups: (1) control; (2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and (3) vagotomy. O(3) inhalation resulted in a significant increase in lung resistance (R(L)) and an exaggerated response to subsequent allergen challenge. PCT abolished the O(3)-induced increase in R(L) and significantly reduced the increase in R(L) induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O(3) inhalation and subsequent challenge with allergen. In this model of O(3) exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge

    PubMed Central

    Schelegle, Edward S.; Walby, William F.

    2012-01-01

    Brown-Norway rats (n = 113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O3) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0 ppm O3 for 8 hours. There were three groups: 1) control; 2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and 3) vagotomy. O3 inhalation resulted in a significant increase in lung resistance (RL) and an exaggerated response to subsequent allergen challenge. PCT abolished the O3-induced increase in RL and significantly reduced the increase in RL induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O3 inhalation and subsequent challenge with allergen. In this model of O3 exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. PMID:22525484

  1. Effect of vagotomy and vagal cooling on bronchoconstrictor response to substance P in sheep.

    PubMed

    Corcoran, B M; Haigh, A L

    1995-10-01

    The bronchoconstrictor effect of intravenous substance P can be antagonised by atropine pre-treatment in several species, and we have previously reported this finding in anaesthetised sheep. In the present study, we have assessed the effect of cooling the right vagus after sectioning the left vagus (n = 6), and bilateral vagotomy (n = 7) on the bronchoconstrictor response to a single intravenous dose of substance P (SP) (0.3-1.0 mumol/kg) in anaesthetized female sheep aged 6 to 12 months. Respiratory parameters including tidal volume, flow and transpulmonary pressure pressure were measured, from which pulmonary resistance (RL; cmH2O.1(-1).s) and dynamic compliance (CDyn; ml.cmH2O(-1) were calculated. Systemic arterial pressures were also measured. Vagal cooling significantly attenuated the bronchoconstrictor response to SP at 7 degrees C (RL P < 0.01; Cdyn P < 0.001). A further reduction in the response to SP occurred at 3 degrees C, but this was not statistically significantly different from the response at 7 degrees C. Vagotomy abolished the response to SP. SP caused mild, but statistically insignificant, hypotension (119.7 vs. 107.7 mmHg). These results suggest SP causes bronchoconstriction in the anaesthetised sheep by vagal reflex mechanisms, involving stimulation of myelinated nerve fibre endings.

  2. The role of cardiac vagal tone and inhibitory control in pre-schoolers' listening comprehension.

    PubMed

    Scrimin, Sara; Patron, Elisabetta; Florit, Elena; Palomba, Daniela; Mason, Lucia

    2017-12-01

    This study investigated the role of basal cardiac activity and inhibitory control at the beginning of the school year in predicting oral comprehension at the end of the year in pre-schoolers. Forty-three, 4-year-olds participated in the study. At the beginning of the school year children's electrocardiogram at rest was registered followed by the assessment of inhibitory control as well as verbal working memory and verbal ability. At the end of the year all children were administered a listening comprehension ability measure. A stepwise regression showed a significant effect of basal cardiac vagal tone in predicting listening comprehension together with inhibitory control and verbal ability. These results are among the first to show the predictive role of basal cardiac vagal tone and inhibitory control in pre-schoolers' oral text comprehension, and offer new insight into the association between autonomic regulation of the heart, inhibitory control, and cognitive activity at a young age. © 2017 Wiley Periodicals, Inc.

  3. Cardiac vagal control and children’s adaptive functioning: A meta-analysis

    PubMed Central

    Graziano, Paulo; Derefinko, Karen

    2014-01-01

    Polyvagal theory has influenced research on the role of cardiac vagal control, indexed by respiratory sinus arrhythmia withdrawal (RSA-W) during challenging states, in children’s self-regulation. However, it remains unclear how well RSA-W predicts adaptive functioning (AF) outcomes and whether certain caveats of measuring RSA (e.g., respiration) significantly impact these associations. A meta-analysis of 44 studies (n = 4,996 children) revealed small effect sizes such that greater levels of RSA-W were related to fewer externalizing, internalizing, and cognitive/academic problems. In contrast, RSA-W was differentially related to children’s social problems according to sample type (community vs. clinical/at-risk). The relations between RSA-W and children’s AF outcomes were stronger among studies that co-varied baseline RSA and in Caucasian children (no effect was found for respiration). Children from clinical/at-risk samples displayed lower levels of baseline RSA and RSA-W compared to children from community samples. Theoretical/practical implications for the study of cardiac vagal control are discussed. PMID:23648264

  4. Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat

    PubMed Central

    2010-01-01

    Background Cardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR). Although CVPN receive GABAergic and glutamatergic inputs, likely involved in respiratory and reflex modulation of HR respectively, little else is known regarding the functions controlled by ionotropic inputs. Activation of g-protein coupled receptors (GPCR) alters these inputs, but the functional consequence is largely unknown. The present study aimed to delineate how ionotropic GABAergic, glycinergic and glutamatergic inputs contribute to the tonic and reflex control of HR and in particular determine which receptor subtypes were involved. Furthermore, we wished to establish how activation of the 5-HT1A GPCR affects tonic and reflex control of HR and what ionotropic interactions this might involve. Results Microinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN. Conclusions We conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN. PMID:20939929

  5. Ghrelin is involved in the paracrine communication between neurons and glial cells.

    PubMed

    Avau, B; De Smet, B; Thijs, T; Geuzens, A; Tack, J; Vanden Berghe, P; Depoortere, I

    2013-09-01

    Ghrelin is the only known peripherally active orexigenic hormone produced by the stomach that activates vagal afferents to stimulate food intake and to accelerate gastric emptying. Vagal sensory neurons within the nodose ganglia are surrounded by glial cells, which are able to receive and transmit chemical signals. We aimed to investigate whether ghrelin activates or influences the interaction between both types of cells. The effect of ghrelin was compared with that of leptin and cholecystokinin (CCK). Cultures of rat nodose ganglia were characterized by immunohistochemistry and the functional effects of peptides, neurotransmitters, and pharmacological blockers were measured by Ca(2+) imaging using Fluo-4-AM as an indicator. Neurons responded to KCl and were immunoreactive for PGP-9.5 whereas glial cells responded to lysophosphatidic acid and had the typical SOX-10-positive nuclear staining. Neurons were only responsive to CCK (31 ± 5%) whereas glial cells responded equally to the applied stimuli: ghrelin (27 ± 2%), leptin (21 ± 2%), and CCK (30 ± 2%). In contrast, neurons stained more intensively for the ghrelin receptor than glial cells. ATP induced [Ca(2+) ]i rises in 90% of the neurons whereas ACh and the NO donor, SIN-1, mainly induced [Ca(2+) ]i changes in glial cells (41 and 51%, respectively). The percentage of ghrelin-responsive glial cells was not affected by pretreatment with suramin, atropine, hexamethonium or 1400 W, but was reduced by l-NAME and by tetrodotoxin. Neurons were shown to be immunoreactive for neuronal NO-synthase (nNOS). Our data show that ghrelin induces Ca(2+) signaling in glial cells of the nodose ganglion via the release of NO originating from the neurons. © 2013 John Wiley & Sons Ltd.

  6. Infant diet, gender and the development of vagal tone stability during the first two years of life

    Postnatal nutrition influences neurodevelopment, including autonomic nervous system components associated with cardiac control. In this study resting vagal tone (V) was measured quarterly during infancy and at 2 years in 146 breast-fed, 143 milk formula-fed, and 137 soy formula-fed infants. Stabilit...

  7. Low to high frequency ratio of heart rate variability spectra fails to describe sympatho-vagal balance in cardiac patients.

    PubMed

    Milicević, Goran

    2005-06-01

    Heart rate variability (HRV) reflects an influence of autonomic nervous system on heart work. In healthy subjects, ratio between low and high frequency components (LF/HF ratio) of HRV spectra represents a measure of sympatho-vagal balance. The ratio was defined by the authorities as an useful clinical tool, but it seems that it fails to summarise sympatho-vagal balance in a clinical setting. Value of the method was re-evaluated in several categories of cardiac patients. HRV was analysed from 24-hour Holter ECGs in 132 healthy subjects, and 2159 cardiac patients dichotomised by gender, median of age, diagnosis of myocardial infarction or coronary artery surgery, left ventricular systolic function and divided by overall HRV into several categories. In healthy subjects, LF/HF ratio correlated with overall HRV negatively, as expected. The paradoxical finding was obtained in cardiac patients; the lower the overall HRV and the time-domain indices of vagal modulation activity were the lower the LF/HF ratio was. If used as a measure of sympatho-vagal balance, long-term recordings of LF/HF ratio contradict to clinical finding and time-domain HRV indices in cardiac patients. The ratio cannot therefore be used as a reliable marker of autonomic activity in a clinical setting.

  8. Mother-Infant Vagal Regulation in the Face-to-Face Still-Face Paradigm is Moderated by Maternal Sensitivity

    ERIC Educational Resources Information Center

    Moore, Ginger A.; Hill-Soderlund, Ashley L.; Propper, Cathi B.; Calkins, Susan D.; Mills-Koonce, W. Roger.; Cox, Martha J.

    2009-01-01

    Parents' physiological regulation may support infants' regulation. Mothers (N=152) and 6-month-old male and female infants were observed in normal and disrupted social interaction. Affect was coded at 1-s intervals and vagal tone measured as respiratory sinus arrhythmia (RSA). Maternal sensitivity was assessed in free play. Mothers and infants…

  9. Infant diet, gender and the normative development of vagal tone and heart period during the first two years of life

    Relationships between early postnatal diet and the development of cardiac regulation were studied using resting vagal tone and heart period measures obtained quarterly during infancy and at 2 years in 158 breast-fed, 159 milk formula-fed, and 148 soy formula-fed infants. Both measures increased acro...

  10. Effect of endogenous tachykinins on neuro-effector transmission of vagal nerve in guinea-pig tracheal tissue.

    PubMed

    Aizawa, H; Miyazaki, N; Inoue, H; Ikeda, T; Shigematsu, N

    1990-01-01

    To elucidate the effect of endogenous tachykinins on neuro-effector transmission of vagal nerves, we performed in vitro experiments using guinea-pig tracheal smooth muscle. The subthreshold dose (the highest dose which did not induce any smooth muscle contraction) of capsaicin (10(-8) to 10(-7) M) increased the amplitudes of contractions evoked by electrical field stimulation (EFS) significantly, but not those by acetylcholine (ACh). The inhibitor of neutral endopeptidase, phosphoramidon (10(-7) to 10(-6) M), increased the contractions evoked by EFS significantly. The inhibitor of cholinesterase, physostigmine (10(-6) to 10(-5) M), induced smooth muscle contractions, but such contractions were inhibited by atropine, suggesting the spontaneous release of ACh from the vagal nerve terminals. The subthreshold dose of substance P or capsaicin increased the contractions evoked by physostigmine. These results indicated that endogenous tachykinins increase the spontaneous ACh release as well as the ACh release in response to vagal stimulation from the nerve terminals. Furthermore, it is suggested that the excitatory effects of the tachykinins on the vagal neuro-effector transmission may be modulated by neutral endopeptidase in the guinea pig.

  11. Vagal Regulation, Cortisol, and Sleep Disruption in Women with Metastatic Breast Cancer

    PubMed Central

    Palesh, Oxana; Zeitzer, Jamie M.; Conrad, Ansgar; Giese-Davis, Janine; Mustian, Karen M.; Popek, Varinia; Nga, Karen; Spiegel, David

    2008-01-01

    Study Objectives: To determine the relationship between hypothalamic pituitary axis (HPA) dysregulation, vagal functioning, and sleep problems in women with metastatic breast cancer. Design: Sleep was assessed by means of questionnaires and wrist actigraphy for 3 consecutive nights. The ambulatory, diurnal variation in salivary cortisol levels was measured at 5 time points over 2 days. Vagal regulation was assessed via respiratory sinus arrhythmia (RSATF) during the Trier Social Stress Task. Participants: Ninety-nine women (54.6 ± 9.62 years) with metastatic breast cancer. Results: Longer nocturnal wake episodes (r = 0.21, p = 0.04, N = 91) were associated with a flatter diurnal cortisol slope. Sleep disruption was also associated with diminished RSATF. Higher RSA baseline scores were significantly correlated with higher sleep efficiency (r = 0.39, p = 0.001, N = 68) and correspondingly lower levels of interrupted sleep (waking after sleep onset, WASO; r = −0.38, p = 0.002, N = 68), lower average length of nocturnal wake episodes (r = −0.43, p < 0.001, N = 68), and a lower self-reported number of hours of sleep during a typical night (r = −0.27, p = 0.02, N = 72). Higher RSA AUC was significantly related to higher sleep efficiency (r = 0.45, p < 0.001, N = 64), and a correspondingly lower number of wake episodes (r = −0.27, p = 0.04, N = 64), lower WASO (r = −0.40, p = 0.001, N = 64), and with lower average length of nocturnal wake episodes (r = −0.41, p = 0.001, N = 64). While demographics, disease severity, and psychological variables all explained some portion of the development of sleep disruption, 4 of the 6 sleep parameters examined (sleep efficiency, WASO, mean number of waking episodes, average length of waking episode) were best explained by RSA. Conclusions: These data provide preliminary evidence for an association between disrupted nocturnal sleep and reduced RSA the subsequent day, confirming an association between disrupted nocturnal

  12. Addictive neurons

    PubMed Central

    Kodirov, Sodikdjon A.

    2017-01-01

    Since the reward center is considered to be the area tegmentalis ventralis of the hypothalamus, logically its neurons could mainly be responsible for addiction. However, the literature asserts that almost any neurons of CNS can respond to one or another addictive compound. Obviously not only addictive nicotine, but also alcohol, amphetamine, cannabis, cocaine, heroin and morphine may influence dopaminergic cells alone in VTA. Moreover, paradoxically some of these drugs ameliorate symptoms, counterbalance syndromes, cure diseases and improve health, not only those related to the CNS and in adults, but also almost all other organs and in children, e.g. epilepsy. PMID:28649663

  13. [Mirror neurons].

    PubMed

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  14. Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

    PubMed Central

    Meyers, Kelly; Lim, Audrey; Dye, Matthew; Pak, Diana; Rinaman, Linda; Yates, Bill J.

    2014-01-01

    Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew. PMID:24430885

  15. Age-specific associations between cardiac vagal activity and functional somatic symptoms: a population-based study.

    PubMed

    Tak, Lineke M; Janssens, Karin A M; Dietrich, Andrea; Slaets, Joris P J; Rosmalen, Judith G M

    2010-01-01

    Functional somatic symptoms (FSS) are symptoms not explained by underlying organic pathology. It has frequently been suggested that dysfunction of the autonomic nervous system (ANS) contributes to the development of FSS. We hypothesized that decreased cardiac vagal activity is cross-sectionally and prospectively associated with the number of FSS in the general population. This study was performed in a population-based cohort of 774 adults (45.1% male, mean age +/- SD 53.5 +/- 10.7 years). Participants completed the somatization section of the Composite International Diagnostic Interview surveying the presence of 43 FSS. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF), reflecting cardiac vagal activity. Follow-up measurements of HRV-HF and FSS were performed approximately 2 years later. Linear regression analyses, with adjustments for gender, age, body mass index, anxiety, depression, smoking, alcohol use, and frequency of exercise, revealed an interaction of cardiac vagal activity with age: HRV-HF was negatively associated with FSS in adults 52 years (beta = 0.13, t = 2.51, p = 0.012). Longitudinal analysis demonstrated a similar pattern. Decreased cardiac vagal activity is associated with a higher number of FSS in adults aged vagal activity and FSS in adults aged >52 years needs further exploration. The role of age should be acknowledged in future studies on ANS function in the etiology of FSS. (c) 2010 S. Karger AG, Basel.

  16. Cardiac Vagal Control and Depressive Symptoms: The Moderating Role of Sleep Quality

    PubMed Central

    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

  17. Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or adverse effect of vagal nerve stimulation?

    PubMed

    Akman, Cigdem; Riviello, James J; Madsen, Joseph R; Bergin, Ann M

    2003-06-01

    Sensory symptoms are commonly seen in association with focal epilepsy, but viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main clinical manifestation. With the introduction of vagal nerve stimulation (VNS) for medically refractory epilepsy, viscerosensory symptoms commonly occur as an adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local neck or throat pain, and cough are the most common adverse effects seen during active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a tingling sensation of the neck and throat is directly related to stimulation intensity. We present a case in which recurrent pharyngeal sensations caused a diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and correlating this with clinical symptoms helped determine the etiology of the recurrent sensory symptoms.

  18. Thy1.2 YFP-16 Transgenic Mouse Labels a Subset of Large-Diameter Sensory Neurons that Lack TRPV1 Expression

    PubMed Central

    Taylor-Clark, Thomas E.; Wu, Kevin Y.; Thompson, Julie-Ann; Yang, Kiseok; Bahia, Parmvir K.; Ajmo, Joanne M.

    2015-01-01

    The Thy1.2 YFP-16 mouse expresses yellow fluorescent protein (YFP) in specific subsets of peripheral and central neurons. The original characterization of this model suggested that YFP was expressed in all sensory neurons, and this model has been subsequently used to study sensory nerve structure and function. Here, we have characterized the expression of YFP in the sensory ganglia (DRG, trigeminal and vagal) of the Thy1.2 YFP-16 mouse, using biochemical, functional and anatomical analyses. Despite previous reports, we found that YFP was only expressed in approximately half of DRG and trigeminal neurons and less than 10% of vagal neurons. YFP-expression was only found in medium and large-diameter neurons that expressed neurofilament but not TRPV1. YFP-expressing neurons failed to respond to selective agonists for TRPV1, P2X2/3 and TRPM8 channels in Ca2+ imaging assays. Confocal analysis of glabrous skin, hairy skin of the back and ear and skeletal muscle indicated that YFP was expressed in some peripheral terminals with structures consistent with their presumed non-nociceptive nature. In summary, the Thy1.2 YFP-16 mouse expresses robust YFP expression in only a subset of sensory neurons. But this mouse model is not suitable for the study of nociceptive nerves or the function of such nerves in pain and neuropathies. PMID:25746468

  19. Comparison of spontaneous vs. metronome-guided breathing on assessment of vagal modulation using RR variability.

    PubMed

    Bloomfield, D M; Magnano, A; Bigger, J T; Rivadeneira, H; Parides, M; Steinman, R C

    2001-03-01

    R-R interval variability (RR variability) is increasingly being used as an index of autonomic activity. High-frequency (HF) power reflects vagal modulation of the sinus node. Since vagal modulation occurs at the respiratory frequency, some investigators have suggested that HF power cannot be interpreted unless the breathing rate is controlled. We hypothesized that HF power during spontaneous breathing would not differ significantly from HF power during metronome-guided breathing. We measured HF power during spontaneous breathing in 20 healthy subjects and 19 patients with heart disease. Each subject's spontaneous breathing rate was determined, and the calculation of HF power was repeated with a metronome set to his or her average spontaneous breathing rate. There was no significant difference between the logarithm of HF power measured during spontaneous and metronome-guided breathing [4.88 +/- 0.29 vs. 5.29 +/- 0.30 ln(ms(2)), P = 0.32] in the group as a whole and when patients and healthy subjects were examined separately. We did observe a small (9.9%) decrease in HF power with increasing metronome-guided breathing rates (from 9 to 20 breaths/min). These data indicate that HF power during spontaneous and metronome-guided breathing differs at most by very small amounts. This variability is several logarithmic units less than the wide discrepancies observed between healthy subjects and cardiac patients with a heterogeneous group of cardiovascular disorders. In addition, HF power is relatively constant across the range of typical breathing rates. These data indicate that there is no need to control breathing rate to interpret HF power when RR variability (and specifically HF power) is used to identify high-risk cardiac patients.

  20. Depression is associated with increased vagal withdrawal during unpleasant emotional imagery after cardiac surgery.

    PubMed

    Patron, Elisabetta; Messerotti Benvenuti, Simone; Favretto, Giuseppe; Gasparotto, Renata; Palomba, Daniela

    2015-05-01

    The aim of this study was to examine the influence of depression on heart rate and heart rate variability (HRV) during emotional imagery in patients after cardiac surgery. Based on the scores of the Center for Epidemiological Studies of Depression (CES-D) scale, 28 patients after cardiac surgery were assigned either to the group with depression (CES-D scores ≥ 16; N = 14) or the one without depression (CES-D scores<16; N = 14). Each patient completed a rest period and an emotional imagery including pleasant, neutral and unpleasant scripts. Inter-beat intervals (IBIs) and HRV were measured during the entire protocol. Compared to nondepressed patients, those with depression had greater reductions in high frequency expressed in normalized units (HF n.u.) during the imaging of the unpleasant script (p = .003, Cohen's d = 1.34). Moreover, HF n.u. were lower during the imaging of the unpleasant script than the pleasant one in depressed patients only (p = .020, Cohen's d = 0.55). CES-D scores were also inversely correlated with residualized changes in IBIs (r = -.38, p = .045) and HF n.u. (r = -.49, p = .008) from rest to the imaging of the unpleasant script. The relationship between depression and increased vagal withdrawal during unpleasant emotional imagery extends to patients after cardiac surgery. The present study suggests that increased vagal withdrawal to negative emotions in patients after cardiac surgery may mediate the conferral of cardiac risk by depression. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

    PubMed

    Schulte, Astrid; Lichtenstern, Christoph; Henrich, Michael; Weigand, Markus A; Uhle, Florian

    2014-05-15

    During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion. Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Effects of vagal deafferentation on oesophageal motility and transit in the sheep.

    PubMed Central

    Falempin, M; Madhloum, A; Rousseau, J P

    1986-01-01

    Effects of vagal deafferentation on oesophageal motility and transit were studied in conscious sheep by recording the electromyographic activity of different parts of oesophagus during swallowing of saliva, or balloons inflated with 20 ml of air. Surgical isolation and subsequent sectioning of the nodose ganglion, leaving the bundles of motor fibres intact, can be performed in sheep. Division of both ganglia led to immediate death of sheep. However, vagal deafferentation of the thoracic oesophagus could be achieved by sectioning the thoracic vagus nerve in association with sectioning the contralateral nodose ganglion. The sectioning of one vagus nerve did not affect primary oesophageal peristalsis during swallowing of saliva or of a bolus. Balloons inflated in the pharyngeal cavity and left free to move caudally, failed to pass into the stomach within the normal time of 2-2.3 s in only 4-16% of the tests. In these cases, they were always stopped in the thoracic oesophagus. Following total deafferentation of the thoracic oesophagus, balloons were prevented from being propelled into the stomach in each test. They were stopped for several minutes at the beginning of the deafferented part of the oesophagus. Electromyographic activity recorded from the deafferented part was reduced during swallowing of balloons or saliva. Deafferentation was confirmed by the failure of the presumed deafferented segment of oesophagus to respond to distension. These experiments provide direct evidence that the vagus carries information from the oesophagus which influences the central pattern generator during swallowing of a bolus or saliva. In sheep, this feed-back is essential for the effective swallowing of a bolus although not for saliva. PMID:3723412

  3. Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels.

    PubMed

    Mizuno, Masaki; Kamiya, Atsunori; Kawada, Toru; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru

    2008-12-01

    Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

  4. Role of the vagal afferents in substance P-induced respiratory responses in anaesthetized rabbits.

    PubMed

    Prabhakar, N R; Runold, M; Yamamoto, Y; Lagercrantz, H; Cherniack, N S; von Euler, C

    1987-09-01

    Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Neurons other than motor neurons in motor neuron disease.

    PubMed

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  6. Optogenetic approaches to characterize the long-range synaptic pathways from the hypothalamus to brain stem autonomic nuclei

    PubMed Central

    Piñol, Ramón A.; Bateman, Ryan; Mendelowitz, David

    2012-01-01

    Recent advances in optogenetic methods demonstrate the feasibility of selective photoactivation at the soma of neurons that express channelrhodopsin-2 (ChR2), but a comprehensive evaluation of different methods to selectively evoke transmitter release from distant synapses using optogenetic approaches is needed. Here we compared different lentiviral vectors, with sub-population-specific and strong promoters, and transgenic methods to express and photostimulate ChR2 in the long-range projections of paraventricular nucleus of the hypothalamus (PVN) neurons to brain stem cardiac vagal neurons (CVNs). Using PVN subpopulation-specific promoters for vasopressin and oxytocin, we were able to depolarize the soma of these neurons upon photostimulation, but these promoters were not strong enough to drive sufficient expression for optogenetic stimulation and synaptic release from the distal axons. However, utilizing the synapsin promoter photostimulation of distal PVN axons successfully evoked glutamatergic excitatory post-synaptic currents in CVNs. Employing the Cre/loxP system, using the Sim-1 Cre-driver mouse line, we found that the Rosa-CAG-LSL-ChR2-EYFP Cre-responder mice expressed higher levels of ChR2 than the Rosa-CAG-LSL-ChR2-tdTomato line in the PVN, judged by photo-evoked currents at the soma. However, neither was able to drive sufficient expression to observe and photostimulate the long-range projections to brainstem autonomic regions. We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons. This approach can be very useful to study important hypothalamus-brainstem connections, and can be easily modified to selectively activate other long-range projections within the brain. PMID:22890236

  7. Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia.

    PubMed

    García-Pedraza, José Ángel; García, Mónica; Martín, María Luisa; Eleno, Nélida; Morán, Asunción

    2017-01-01

    5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg·kg·d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 μg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 μg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 μg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB-258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19-induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor.

  8. Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats.

    PubMed

    Shen, Ling; Wang, David Q-H; Lo, Chunmin C; Arnold, Myrtha; Tso, Patrick; Woods, Stephen C; Liu, Min

    2015-12-01

    Ginsenoside Rb1 (Rb1) reduces food intake in both lean and high-fat diet induced-obese rats; however, the sites and/or mediation of the eating-suppressive effect of Rb1 have not previously been identified. We hypothesized that intraperitoneally (ip) administered Rb1 exerts its anorectic action by enhancing sensitivity to satiation signals, such as cholecystokinin (CCK), and/or that it acts through vagal afferent nerves that relay the satiating signaling to the hindbrain. To test these hypotheses, we gave ip bolus doses of Rb1 (2.5-10.0mg/kg) and CCK-8 (0.125-4.0μg/kg) alone or in combination and assessed food intake in rats. Low doses of Rb1 (2.5mg/kg) or CCK-8 (0.125μg/kg) alone had no effect on food intake whereas higher doses did. When these subthreshold doses of Rb1 and CCK-8 were co-administered, the combination significantly reduced food intake relative to saline controls, and this effect was attenuated by lorglumide, a selective CCK1-receptor antagonist. Interestingly, lorglumide blocked food intake induced by an effective dose of CCK-8 alone, but not by Rb1 alone, suggesting that Rb1's anorectic effect is independent of the CCK1 receptor. To determine whether peripherally administered Rb1 suppresses feeding via abdominal vagal nerves, we evaluated the effect of ip Rb1 injection in subdiaphragmatic vagal deafferentation (SDA) and control rats. Rb1's effect on food intake was significantly attenuated in SDA rats, compared with that in SHAM controls. These data indicate that the vagal afferent system is the major pathway conveying peripherally administered Rb1's satiation signal. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

    PubMed Central

    Murphy, Michelle C.; Fox, Edward A.

    2007-01-01

    The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

  10. Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs.

    PubMed

    Uemura, Kazunori; Inagaki, Masashi; Zheng, Can; Kawada, Toru; Li, Meihua; Fukumitsu, Masafumi; Sugimachi, Masaru

    2017-04-01

    Ivabradine, a bradycardic agent, has been shown to stably reduce patient's heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility. In 16 anesthetized dogs, cervical vagal nerves were prepared for electrical stimulation (VS). AF induction rate (AFIR) was determined by atrial burst pacing. HR, atrial action potential duration (APD), atrial effective refractory period (ERP), and AFIR were obtained consecutively at baseline, during delivery of VS (VS alone), after intravenous injection of ivabradine 0.5 mg/kg (n = 8, ivabradine group) or saline (n = 8, saline group), and again during VS delivery (drug+VS). In the ivabradine group, ivabradine alone significantly lowered HR compared to baseline, while ivabradine+VS significantly lowered HR compared to VS alone. Contrary to expectations, there were no significant differences in trends of APD, temporal dispersion of APD, ERP, and AFIR between ivabradine and saline groups. Irrespective of whether ivabradine or saline was injected, VS significantly shortened APD and ERP, and increased AFIR. Interestingly, although bradycardia in response to ivabradine injection was more intense than that to VS alone, AFIR was significantly lower after ivabradine injection than during VS alone. We conclude that, despite its intense bradycardic effect, acute ivabradine treatment does not increase AF inducibility irrespective of underlying vagal activity. This study may constitute support for the safety of using ivabradine in the setting of acute cardiac

  11. The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.

    PubMed

    Sarr, Michael G; Billington, Charles J; Brancatisano, Roy; Brancatisano, Anthony; Toouli, James; Kow, Lilian; Nguyen, Ninh T; Blackstone, Robin; Maher, James W; Shikora, Scott; Reeds, Dominic N; Eagon, J Christopher; Wolfe, Bruce M; O'Rourke, Robert W; Fujioka, Ken; Takata, Mark; Swain, James M; Morton, John M; Ikramuddin, Sayeed; Schweitzer, Michael; Chand, Bipan; Rosenthal, Raul

    2012-11-01

    Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n = 192) or control (n = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m(2), and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥ 12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

  12. Evoked Pain Analgesia in Chronic Pelvic Pain Patients using Respiratory-gated Auricular Vagal Afferent Nerve Stimulation

    PubMed Central

    Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D.

    2012-01-01

    Objective Previous Vagus Nerve Stimulation (VNS) studies have demonstrated anti-nociceptive effects, and recent non-invasive approaches; termed transcutaneous-VNS, or t-VNS, have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design counterbalanced, crossover study. Patients patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes We evaluated evoked pain analgesia for Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) compared with Non-Vagal Auricular Stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least one week apart. Outcome measures included deep tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N=15 CPP patients, compared to NVAS, with moderate to large effect sizes (eta2>0.2). Conclusion Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS produced promising anti-nociceptive effects for QST outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. PMID:22568773

  13. Repeated arterial occlusion, delta-opioid receptor (DOR) plasticity and vagal transmission within the sinoatrial node of the anesthetized dog.

    PubMed

    Deo, Shekhar H; Barlow, Matthew A; Gonzalez, Leticia; Yoshishige, Darice; Caffrey, James L

    2009-01-01

    Brief interruptions in coronary blood flow precondition the heart, engage delta-opioid receptor (DOR) mechanisms and reduce the damage that typically accompanies subsequent longer coronary occlusions. Repeated short occlusions of the sinoatrial (SA) node artery progressively raised nodal methionine-enkephalin-arginine-phenylalanine (MEAP) and improved vagal transmission during subsequent long occlusions in anesthetized dogs. The DOR type-1 (DOR-1) antagonist, BNTX reversed the vagotonic effect. Higher doses of enkephalin interrupted vagal transmission through a DOR-2 mechanism. The current study tested whether the preconditioning (PC) protocol, the later occlusion or a combination of both was required for the vagotonic effect. The study also tested whether evolving vagotonic effects included withdrawal of competing DOR-2 vagolytic influences. Vagal transmission progressively improved during successive SA nodal artery occlusions. The vagotonic effect was absent in sham animals and after DOR-1 blockade. After completing the PC protocol, exogenously applied vagolytic doses of MEAP reduced vagal transmission under both normal and occluded conditions. The magnitude of these DOR-2 vagolytic effects was small compared to controls and repeated MEAP challenges rapidly eroded vagolytic responses further. Prior DOR-1 blockade did not alter the PC mediated, progressive loss of DOR-2 vagolytic responses. In conclusion, DOR-1 vagotonic responses evolved from signals earlier in the PC protocol and erosion of competing DOR-2 vagolytic responses may have contributed to an unmasking of vagotonic responses. The data support the hypothesis that PC and DOR-2 stimulation promote DOR trafficking, and down regulation of the vagolytic DOR-2 phenotype in favor of the vagotonic DOR-1 phenotype. DOR-1 blockade may accelerate the process by sequestering newly emerging receptors.

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

    NASA Technical Reports Server (NTRS)

    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.

  15. At the heart of morality lies neuro-visceral integration: lower cardiac vagal tone predicts utilitarian moral judgment

    PubMed Central

    Kappes, Andreas; Rho, Yeojin; Van Bavel, Jay J.

    2016-01-01

    To not harm others is widely considered the most basic element of human morality. The aversion to harm others can be either rooted in the outcomes of an action (utilitarianism) or reactions to the action itself (deontology). We speculated that the human moral judgments rely on the integration of neural computations of harm and visceral reactions. The present research examined whether utilitarian or deontological aspects of moral judgment are associated with cardiac vagal tone, a physiological proxy for neuro-visceral integration. We investigated the relationship between cardiac vagal tone and moral judgment by using a mix of moral dilemmas, mathematical modeling and psychophysiological measures. An index of bipolar deontology-utilitarianism was correlated with resting heart rate variability (HRV)—an index of cardiac vagal tone—such that more utilitarian judgments were associated with lower HRV. Follow-up analyses using process dissociation, which independently quantifies utilitarian and deontological moral inclinations, provided further evidence that utilitarian (but not deontological) judgments were associated with lower HRV. Our results suggest that the functional integration of neural and visceral systems during moral judgments can restrict outcome-based, utilitarian moral preferences. Implications for theories of moral judgment are discussed. PMID:27317926

  16. At the heart of morality lies neuro-visceral integration: lower cardiac vagal tone predicts utilitarian moral judgment.

    PubMed

    Park, Gewnhi; Kappes, Andreas; Rho, Yeojin; Van Bavel, Jay J

    2016-10-01

    To not harm others is widely considered the most basic element of human morality. The aversion to harm others can be either rooted in the outcomes of an action (utilitarianism) or reactions to the action itself (deontology). We speculated that the human moral judgments rely on the integration of neural computations of harm and visceral reactions. The present research examined whether utilitarian or deontological aspects of moral judgment are associated with cardiac vagal tone, a physiological proxy for neuro-visceral integration. We investigated the relationship between cardiac vagal tone and moral judgment by using a mix of moral dilemmas, mathematical modeling and psychophysiological measures. An index of bipolar deontology-utilitarianism was correlated with resting heart rate variability (HRV)-an index of cardiac vagal tone-such that more utilitarian judgments were associated with lower HRV. Follow-up analyses using process dissociation, which independently quantifies utilitarian and deontological moral inclinations, provided further evidence that utilitarian (but not deontological) judgments were associated with lower HRV. Our results suggest that the functional integration of neural and visceral systems during moral judgments can restrict outcome-based, utilitarian moral preferences. Implications for theories of moral judgment are discussed. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  17. Cardiac vagal regulation in infancy predicts executive function and social competence in preschool: Indirect effects through language.

    PubMed

    Whedon, Margaret; Perry, Nicole B; Calkins, Susan D; Bell, Martha Ann

    2018-05-21

    Parasympathetic nervous system functioning in infancy may serve a foundational role in the development of cognitive and socioemotional skills (Calkins, 2007). In this study (N = 297), we investigated the potential indirect effects of cardiac vagal regulation in infancy on children's executive functioning and social competence in preschool via expressive and receptive language in toddlerhood. Vagal regulation was assessed at 10 months during two attention conditions (social, nonsocial) via task-related changes in respiratory sinus arrhythmia (RSA). A path analysis revealed that decreased RSA from baseline in the nonsocial condition and increased RSA in the social condition were related to larger vocabularies in toddlerhood. Additionally, children's vocabulary sizes were positively related to their executive function and social competence in preschool. Indirect effects from vagal regulation in both contexts to both 4-year outcomes were significant, suggesting that early advances in language may represent a mechanism through which biological functioning in infancy impacts social and cognitive functioning in childhood. © 2018 Wiley Periodicals, Inc.

  18. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

    PubMed

    Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D

    2012-06-01

    Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Counterbalanced, crossover study. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. Wiley Periodicals, Inc.

  19. Exercise Type Affects Cardiac Vagal Autonomic Recovery After a Resistance Training Session.

    PubMed

    Mayo, Xián; Iglesias-Soler, Eliseo; Fariñas-Rodríguez, Juán; Fernández-Del-Olmo, Miguel; Kingsley, J Derek

    2016-09-01

    Mayo, X, Iglesias-Soler, E, Fariñas-Rodríguez, J, Fernández-del-Olmo, M, and Kingsley, JD. Exercise type affects cardiac vagal autonomic recovery after a resistance training session. J Strength Cond Res 30(9): 2565-2573, 2016-Resistance training sessions involving different exercises and set configurations may affect the acute cardiovascular recovery pattern. We explored the interaction between exercise type and set configuration on the postexercise cardiovagal withdrawal measured by heart rate variability and their hypotensive effect. Thirteen healthy participants (10 repetitions maximum [RM] bench press: 56 ± 10 kg; parallel squat: 91 ± 13 kg) performed 6 sessions corresponding to 2 exercises (Bench press vs. Parallel squat), 2 set configurations (Failure session vs. Interrepetition rest session), and a Control session of each exercise. Load (10RM), volume (5 sets), and rest (720 seconds) were equated between exercises and set configurations. Parallel squat produced higher reductions in cardiovagal recovery vs. Bench press (p = 0.001). These differences were dependent on the set configuration, with lower values in Parallel squat vs. Bench press for Interrepetition rest session (1.816 ± 0.711 vs. 2.399 ± 0.739 Ln HF/IRR × 10, p = 0.002), but not for Failure session (1.647 ± 0.904 vs. 1.808 ± 0.703 Ln HF/IRR × 10, p > 0.05). Set configuration affected the cardiovagal recovery, with lower values in Failure session in comparison with Interrepetition rest (p = 0.027) and Control session (p = 0.022). Postexercise hypotension was not dependent on the exercise type (p > 0.05) but was dependent on the set configuration, with lower values of systolic (p = 0.004) and diastolic (p = 0.011) blood pressure after the Failure session but not after an Interrepetition rest session in comparison with the Control session (p > 0.05). These results suggest that the exercise type and an Interrepetition rest design could blunt the decrease of cardiac vagal activity after

  20. cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice

    PubMed Central

    Blake, Camille B.

    2014-01-01

    Pathologies in which insulin is dysregulated, including diabetes, can disrupt central vagal circuitry, leading to gastrointestinal and other autonomic dysfunction. Insulin affects whole body metabolism through central mechanisms and is transported into the brain stem dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarius (NTS), which mediate parasympathetic visceral regulation. The NTS receives viscerosensory vagal input and projects heavily to the DMV, which supplies parasympathetic vagal motor output. Normally, insulin inhibits synaptic excitation of DMV neurons, with no effect on synaptic inhibition. Modulation of synaptic inhibition in DMV, however, is often sensitive to cAMP-dependent mechanisms. We hypothesized that an effect of insulin on GABAergic synaptic transmission may be uncovered by elevating resting cAMP levels in GABAergic terminals. We used whole cell patch-clamp recordings in brain stem slices from control and diabetic mice to identify insulin effects on inhibitory neurotransmission in the DMV in the presence of forskolin to elevate cAMP levels. In the presence of forskolin, insulin decreased the frequency of inhibitory postsynaptic currents (IPSCs) and the paired-pulse ratio of evoked IPSCs in DMV neurons from control mice. This effect was blocked by brefeldin-A, a Golgi-disrupting agent, or indinavir, a GLUT4 blocker, indicating that protein trafficking and glucose transport were involved. In streptozotocin-treated, diabetic mice, insulin did not affect IPSCs in DMV neurons in the presence of forskolin. Results suggest an impairment of cAMP-induced insulin effects on GABA release in the DMV, which likely involves disrupted protein trafficking in diabetic mice. These findings provide insight into mechanisms underlying vagal dysregulation associated with diabetes. PMID:24990858

  1. Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

    PubMed Central

    Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

    2015-01-01

    Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

  2. Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

    PubMed Central

    Shaw, Albert C.; Jackson, Adam W.; Holmes, Tamra; Thurman, Suzie; Davis, G.R.; McClellan, Andrew D.

    2010-01-01

    In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord. PMID:20510243

  3. Associations of immunometabolic risk factors with symptoms of depression and anxiety: The role of cardiac vagal activity.

    PubMed

    Hu, Mandy X; Penninx, Brenda W J H; de Geus, Eco J C; Lamers, Femke; Kuan, Dora C-H; Wright, Aidan G C; Marsland, Anna L; Muldoon, Matthew F; Manuck, Stephen B; Gianaros, Peter J

    2018-06-18

    This study examined 1) the cross-sectional relationships between symptoms of depression/anxiety and immunometabolic risk factors, and 2) whether these relationships might be explained in part by cardiac vagal activity. Data were drawn from the Adult Health and Behavior registries (n = 1785), comprised of community dwelling adults (52.8% women, aged 30-54). Depressive symptoms were measured with the Center for Epidemiological Studies Depression Scale (CES-D) and the Beck Depression Inventory-II (BDI-II), and anxious symptoms with the Trait Anxiety scale of the State-Trait Anxiety Inventory (STAI-T). Immunometabolic risk factors included fasting levels of triglycerides, high-density lipoproteins, glucose, and insulin, as well as blood pressure, waist circumference, body mass index, C-reactive protein, and interleukin-6. Measures of cardiac autonomic activity were high- and low-frequency indicators of heart rate variability (HRV), standard deviation of normal-to-normal R-R intervals, and the mean of absolute and successive differences in R-R intervals. Higher BDI-II scores, in contrast to CES-D and STAI-T scores, were associated with increased immunometabolic risk and decreased HRV, especially HRV likely reflecting cardiac vagal activity. Decreased HRV was also associated with increased immunometabolic risk. Structural equation models indicated that BDI-II scores may relate to immunometabolic risk via cardiac vagal activity (indirect effect: β = .012, p = .046) or to vagal activity via immunometabolic risk (indirect effect: β = -.015, p = .021). Depressive symptoms, as measured by the BDI-II, but not anxious symptoms, were related to elevated levels of immunometabolic risk factors and low cardiac vagal activity. The latter may exhibit bidirectional influences on one another in a meditational framework. Future longitudinal, intervention, an nonhuman animal work is needed to elucidate the precise and mechanistic pathways linking depressive symptoms

  4. Cardiac vagal control as a prospective predictor of anxiety in women diagnosed with breast cancer.

    PubMed

    Kogan, Anya V; Allen, John J B; Weihs, Karen L

    2012-04-01

    Low cardiac vagal control (CVC) has been associated with state and trait anxiety and anxiety spectrum disorders. Studies indicate that diagnosis and treatments for breast cancer may be associated with anxiety. The current study examined whether CVC prospectively predicted a trajectory of change in anxiety following breast cancer diagnosis. Forty-three women diagnosed with non-metastatic breast cancer completed the Taylor Manifest Anxiety Scale and the Perceived Stress Scale, and a 5-min resting electrocardiographic (ECG) segment was recorded. Self-report measures were completed approximately every 3 months for a year. Respiratory sinus arrhythmia (RSA) significantly predicted the trajectory of change in anxiety over the follow-up period: participants with higher baseline RSA evidenced decreasing anxiety, whereas those with lower baseline RSA had increasing anxiety. These results are consistent with the hypothesis that CVC facilitates the modulation of anxiety in women coping with significant stressors of breast cancer diagnosis and treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Too much of a good thing? Cardiac vagal tone's nonlinear relationship with well-being.

    PubMed

    Kogan, Aleksandr; Gruber, June; Shallcross, Amanda J; Ford, Brett Q; Mauss, Iris B

    2013-08-01

    Parasympathetic regulation of heart rate through the vagus nerve--often measured as resting respiratory sinus arrhythmia or cardiac vagal tone (CVT)--is a key biological correlate of psychological well-being. However, recent theorizing has suggested that many biological and psychological processes can become maladaptive when they reach extreme levels. This raises the possibility that CVT might not have an unmitigated positive relationship with well-being. In line with this reasoning, across 231 adult participants (Mage = 40.02 years; 52% female), we found that CVT was quadratically related to multiple measures of well-being, including life satisfaction and depressive symptoms. Individuals with moderate CVT had higher well-being than those with low or high CVT. These results provide the first direct evidence of a nonlinear relationship between CVT and well-being, adding to a growing body of research that has suggested some biological processes may cease being adaptive when they reach extreme levels. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  6. Blood pressure control with selective vagal nerve stimulation and minimal side effects

    NASA Astrophysics Data System (ADS)

    Plachta, Dennis T. T.; Gierthmuehlen, Mortimer; Cota, Oscar; Espinosa, Nayeli; Boeser, Fabian; Herrera, Taliana C.; Stieglitz, Thomas; Zentner, Joseph

    2014-06-01

    Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

  7. Chronic work stress and decreased vagal tone impairs decision making and reaction time in jockeys.

    PubMed

    Landolt, Kathleen; Maruff, Paul; Horan, Ben; Kingsley, Michael; Kinsella, Glynda; O'Halloran, Paul D; Hale, Matthew W; Wright, Bradley J

    2017-10-01

    The inverse relationship between acute stress and decision-making is well documented, but few studies have investigated the impact of chronic stress. Jockeys work exhaustive schedules and have extremely dangerous occupations, with safe performance requiring quick reaction time and accurate decision-making. We used the effort reward imbalance (ERI) occupational stress model to assess the relationship of work stress with indices of stress physiology and decision-making and reaction time. Jockeys (N=32) completed computerised cognitive tasks (Cogstate) on two occasions; September and November (naturally occurring lower and higher stress periods), either side of an acute stress test. Higher ERI was correlated with the cortisol awakening responses (high stress r=-0.37; low stress r=0.36), and with decrements in decision-making comparable to having a blood alcohol concentration of 0.08 in the high stress period (p<0.001) The LF/HF ratio of heart rate variability impacted the association of ERI with decision-making. Potentially, this may be attributed to a 'tipping point' whereby the higher ERI reported by jockeys in the high stress period decreases vagal tone, which may contribute to reduced decision-making abilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Vagal Nerve Stimulation Evoked Heart Rate Changes and Protection from Cardiac Remodeling.

    PubMed

    Agarwal, Rahul; Mokelke, Eric; Ruble, Stephen B; Stolen, Craig M

    2016-02-01

    This study investigated whether vagal nerve stimulation (VNS) leads to improvements in ischemic heart failure via heart rate modulation. At 7 ± 1 days post left anterior descending artery (LAD) ligation, 63 rats with myocardial infarctions (MI) were implanted with ECG transmitters and VNS devices (MI + VNS, N = 44) or just ECG transmitters (MI, N = 17). VNS stimulation was active from 14 ± 1 days to 8 ± 1 weeks post MI. The average left ventricular (LV) end diastolic volumes at 8 ± 1 weeks were MI = 672.40 μl and MI + VNS = 519.35 μl, p = 0.03. The average heart weights, normalized to body weight (± std) at 14 ± 1 weeks were MI = 3.2 ± 0.6 g*kg(-1) and MI + VNS = 2.9 ± 0.3 g*kg(-1), p = 0.03. The degree of cardiac remodeling was correlated with the magnitude of acute VNS-evoked heart rate (HR) changes. Further research is required to determine if the acute heart rate response to VNS activation is useful as a heart failure biomarker or as a tool for VNS therapy characterization.

  9. Mothers' Vagal Regulation During the Still-Face Paradigm: Normative Reactivity and Impact of Depression Symptoms

    PubMed Central

    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

  10. Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs.

    PubMed

    Coleridge, H M; Coleridge, J C

    1977-04-01

    We recorded impulses from afferent vagal C-fibres (conduction velocities 0.8-2.4 m/sec) arising from endings in the lungs of anesthetized dogs with open chest. Endings were of two types ('pulmonary' and 'bronchial') distinguished by their response and accessibility to capsaicin and phenyl diguanide injected into the right or left atrium. 'Pulmonary' endings, stimulated only by capsaicin and accessible through the pulmonary circulation, have been described previously. 'Bronchial' endings were stimulated by both capsicin and phenyl diguanide and were accessible through the bronchial circulation. Eight of 28 'bronchial' endings were located in large airways within 4 cm of the hilum, and two were in small airways near the edge of the lung. The precise location of the remaining 'bronchial' endings was not determined but we think that many were in the airways. 'Bronchial' endings had a sparse and irregular spontaneous discharge. They were stimulated by the inhalation of 5% histamine aerosol, the evoked discharge having no obvious relation to the phase of ventilation. A few were weakly stimulated by hyperinflating the lungs; deflation was without effect. The function of these endings is unknown.

  11. Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection.

    PubMed

    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 P<.001). Mexico 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

  12. Effort reward imbalance is associated with vagal withdrawal in Danish public sector employees.

    PubMed

    Eller, Nanna Hurwitz; Blønd, Morten; Nielsen, Martin; Kristiansen, Jesper; Netterstrøm, Bo

    2011-09-01

    The current study analyzed the relationship between psychosocial work environment assessed by the Effort Reward Imbalance Model (ERI-model) and heart rate variability (HRV) measured at baseline and again, two years later, as this relationship is scarcely covered by the literature. Measurements of HRV during seated rest were obtained from 231 public sector employees. The associations between the ERI-model, and HRV were examined using a series of mixed effects models. The dependent variables were the logarithmically transformed levels of HRV-measures. Gender and year of measurement were included as factors, whereas age, and time of measurement were included as covariates. Subject was included as a random effect. Effort and effort reward imbalance were positively associated with heart rate and the ratio between low frequency (LF) and high frequency power (HF) and negatively associated with total power (TP) and HF. Reward was positively associated with TP. Adverse psychosocial work environment according to the ERI-model was associated with HRV, especially in the form of vagal withdrawal and most pronounced in women. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis.

    PubMed

    Schelegle, E S; Walby, W F; Mansoor, J K; Chen, A T

    2001-05-01

    Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering-Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

  14. Affective and physiological responses to the suffering of others: compassion and vagal activity.

    PubMed

    Stellar, Jennifer E; Cohen, Adam; Oveis, Christopher; Keltner, Dacher

    2015-04-01

    Compassion is an affective response to another's suffering and a catalyst of prosocial behavior. In the present studies, we explore the peripheral physiological changes associated with the experience of compassion. Guided by long-standing theoretical claims, we propose that compassion is associated with activation in the parasympathetic autonomic nervous system through the vagus nerve. Across 4 studies, participants witnessed others suffer while we recorded physiological measures, including heart rate, respiration, skin conductance, and a measure of vagal activity called respiratory sinus arrhythmia (RSA). Participants exhibited greater RSA during the compassion induction compared with a neutral control (Study 1), another positive emotion (Study 2), and a prosocial emotion lacking appraisals of another person's suffering (Study 3). Greater RSA during the experience of compassion compared with the neutral or control emotion was often accompanied by lower heart rate and respiration but no difference in skin conductance. In Study 4, increases in RSA during compassion positively predicted an established composite of compassion-related words, continuous self-reports of compassion, and nonverbal displays of compassion. Compassion, a core affective component of empathy and prosociality, is associated with heightened parasympathetic activity. (c) 2015 APA, all rights reserved).

  15. Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

    PubMed

    van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

    2016-05-01

    Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may

  16. Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve

    PubMed Central

    Derbenev, Andrei V; Stuart, Thomas C; Smith, Bret N

    2004-01-01

    Cannabinoids bind central type 1 receptors (CB1R) and modify autonomic functions, including feeding and anti-emetic behaviours, when administered peripherally or into the dorsal vagal complex. Western blots and immunohistochemistry indicated the expression of CB1R in the rat dorsal vagal complex, and tissue polymerase chain reaction confirmed that CB1R message was made within the region. To identify a cellular substrate for the central autonomic effects of cannabinoids, whole-cell patch-clamp recordings were made in brainstem slices to determine the effects of CB1R activation on synaptic transmission to neurones of the dorsal motor nucleus of the vagus (DMV). A subset of these neurones was identified as gastric related after being labelled retrogradely from the stomach. The CB1R agonists WIN55,212-2 and anandamide decreased the frequency of spontaneous excitatory or inhibitory postsynaptic currents in a concentration-related fashion, an effect that persisted in the presence of tetrodotoxin. Paired pulse ratios of electrically evoked postsynaptic currents were also increased by WIN55,212-2. The effects of WIN55,212-2 were sensitive to the selective CB1R antagonist AM251. Cannabinoid agonist effects on synaptic input originating from neurones in the nucleus tractus solitarius (NTS) were determined by evoking activity in the NTS with local glutamate application. Excitatory and inhibitory synaptic inputs arising from the NTS were attenuated by WIN55,212-2. Our results indicate that cannabinoids inhibit transfer of synaptic information to the DMV, including that arising from the NTS, in part by acting at receptors located on presynaptic terminals contacting DMV neurones. Inhibition of synaptic input to DMV neurones is likely to contribute to the suppression of visceral motor responses by cannabinoids. PMID:15272041

  17. Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn’s Disease and Irritable Bowel Syndrome

    PubMed Central

    Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

    2014-01-01

    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. PMID

  18. A Little Goes a Long Way: Low Working Memory Load Is Associated with Optimal Distractor Inhibition and Increased Vagal Control under Anxiety.

    PubMed

    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.

  19. A Little Goes a Long Way: Low Working Memory Load Is Associated with Optimal Distractor Inhibition and Increased Vagal Control under Anxiety

    PubMed Central

    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. PMID:28217091

  20. Early determinants of vagal activity at preschool age - With potential dependence on sex.

    PubMed

    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, p<0.001). Smoking before and during pregnancy showed no significant association with HRR in the total sample. However, we found interactions between sex and smoking before and during pregnancy as well as between sex and breastfeeding, suggesting significant associations with HRR only in girls. Besides PA, early 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.

  1. Analysis of factors related to vagally mediated reflex bradycardia during gastrectomy.

    PubMed

    Kim, Duk-Kyung; Ahn, Hyun Joo; Lee, Seung Won; Choi, Ji Won

    2015-12-01

    Because vagally mediated reflex bradycardia occurs frequently during gastrectomy and is potentially harmful, we compared the incidence of clinically significant reflex bradycardia between patients undergoing laparoscopic gastrectomy (LG) and open gastrectomy (OG) and examined whether the type of surgery (OG vs. LG) was an independent risk factor for clinically significant reflex bradycardia. This prospective observational study evaluated 358 adult patients (age 18-70 years) who were undergoing elective OG or LG for gastric cancer resection. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to <50 beats per minute (bpm), or to 50-59 bpm with a systolic blood pressure <70 mmHg, associated with a specific surgical maneuver. If bradycardia or hypotension developed, atropine or ephedrine was administered, in accordance with a predefined treatment protocol. The overall incidence of symptomatic reflex bradycardia was 24.6% (88/358). Univariate analysis revealed the incidence of symptomatic reflex bradycardia in the LG group was significantly lower than that in the OG group [13.0% (13/100) vs. 29.1% (75/258), p = 0.002]. Multivariate logistic regression analysis revealed that the type of surgery (OG vs. LG), advanced age, preoperative bradycardia, type of muscle relaxant (vecuronium vs. rocuronium), no use of intravenous remifentanil, and low core temperature, were independent risk factors for symptomatic reflex bradycardia (odds ratio 3.184; 95% confidence interval 1.490-6.800; p = 0.003). The LG approach was associated with a reduced risk of clinically significant reflex bradycardia compared with the OG approach.

  2. Vi. Marital conflict, vagal regulation, and children's sleep: a longitudinal investigation.

    PubMed

    El-Sheikh, Mona; Hinnant, J Benjamin; Erath, Stephen A

    2015-03-01

    We examined longitudinal relations between adult interpartner conflict (referred to as marital conflict) and children's subsequent sleep minutes and quality assessed objectively via actigraphy, and tested parasympathetic nervous system (PNS) activity indexed through respiratory sinus arrhythmia reactivity (RSA-R) and initial sleep as moderators of predictive associations. At Wave 1 (W1), children (85 boys, 75 girls) with a mean age of 9.43 years (SD=.69) reported on marital conflict, and their sleep was assessed with actigraphs for seven nights. Sleep minutes, sleep efficiency, sleep activity, and number of long wake episodes were derived. RSA-R was measured in response to a lab challenge. Sleep parameters were assessed again 1 year later at Wave 2 (W2; mean age=10.39; SD=.64). Analyses consistently revealed 3-way interactions among W1 marital conflict, sleep, and RSA-R as predictors of W2 sleep parameters. Sleep was stable among children with more sleep minutes and better sleep quality at W1 or low exposure to marital conflict at W1. Illustrating conditional risk, marital conflict predicted increased sleep problems (reduced sleep minutes, worse sleep quality) at W2 among children with poorer sleep at W1 in conjunction with less apt physiological regulation (i.e., lower levels of RSA-R or less vagal withdrawal) at W1. Findings build on the scant literature and underscore the importance of simultaneous consideration of bioregulatory systems (PNS and initial sleep in this study) in conjunction with family processes in the prediction of children's later sleep parameters. © 2015 The Society for Research in Child Development, Inc.

  3. Modified carotid sinus massage using an ultrasonography for maximizing vagal tone: a crossover simulation study.

    PubMed

    Ha, Seung Min; Cho, Young Suk; Cho, Gyu Chong; Jo, Choong Hyun; Ryu, Ji Young

    2015-07-01

    The aim of this study was to ascertain if a modified carotid sinus massage (CSM) using ultrasonography is superior to the conventional CSM for vagal tone generation. This was a prospective, crossover, clinical trial including 30 subjects with sinus rhythm. Participants were paired, and they performed 2 types of CSM to each other. To perform the conventional technique, pressure was exerted at the point where the maximal impulse of the carotid pulse was palpated. In the modified technique, participants localized the point of maximal diameter just above the bifurcation of the common carotid artery using ultrasonography and applied pressure to that point. Mean differences between premaneuver and postmaneuver R-R intervals and heart rates were compared. The distance from the midline of the neck (x distance) to the angle of the mandible (y distance) was measured, and the mean distance between the 2 techniques was compared. The baseline mean premaneuver R-R interval and heart rate did not differ significantly between the 2 techniques. The postmaneuver R-R interval and heart rate as well as the mean R-R interval and heart rate differences were significantly greater in the modified CSM. The mean location determined using the modified CSM was located 0.8 cm lateral and 0.8 cm superior to the mean location of the conventional CSM. The modified CSM using ultrasonography might be more useful than the conventional CSM in reverting episodes of paroxysmal supraventricular tachycardia and may be a suitable alternative for treating the same in the emergency department. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells.

    PubMed

    Uribe, Rosa A; Hong, Stephanie S; Bronner, Marianne E

    2018-01-01

    The enteric nervous system arises from neural crest cells that migrate as chains into and along the primitive gut, subsequently differentiating into enteric neurons and glia. Little is known about the mechanisms governing neural crest migration en route to and along the gut in vivo. Here, we report that Retinoic Acid (RA) temporally controls zebrafish enteric neural crest cell chain migration. In vivo imaging reveals that RA loss severely compromises the integrity and migration of the chain of neural crest cells during the window of time window when they are moving along the foregut. After loss of RA, enteric progenitors accumulate in the foregut and differentiate into enteric neurons, but subsequently undergo apoptosis resulting in a striking neuronal deficit. Moreover, ectopic expression of the transcription factor meis3 and/or the receptor ret, partially rescues enteric neuron colonization after RA attenuation. Collectively, our findings suggest that retinoic acid plays a critical temporal role in promoting enteric neural crest chain migration and neuronal survival upstream of Meis3 and RET in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Plasticity of vagal brainstem circuits in the control of gastrointestinal function

    PubMed Central

    Browning, Kirsteen N; Travagli, R. Alberto

    2010-01-01

    The afferent vagus transmits sensory information from the gastrointestinal (GI) tract and other viscera to the brainstem via a glutamatergic synapse at the level of the nucleus of the solitary tract (NTS). Second order NTS neurons integrate this sensory information with inputs from other CNS regions that regulate autonomic functions and homeostasis. Glutamatergic and GABAergic neurons are responsible for conveying the integrated response to other nuclei, including the adjacent dorsal motor nucleus of the vagus (DMV). The preganglionic neurons in the DMV are the source of the parasympathetic motor response back to the GI tract. The glutamatergic synapse between the NTS and DMV is unlikely to be tonically active in regulating gastric motility and tone although almost all neurotransmitters tested so far modulate transmission at this synapse. In contrast, the tonic inhibitory GABAergic input from the NTS to the DMV appears to be critical in setting the tone of gastric motility and, under basal conditions, is unaffected by many neurotransmitters or neurohormones. This review is based, in part, on a presentation by Dr Browning at the 2009 ISAN meeting in Sydney, Australia and discusses how neurohormones and macronutrients modulate glutamatergic transmission to NTS neurons and GABAergic transmission to DMV neurons in relation to sensory information that is received from the GI tract. These neurohormones and macronutrients appear to exert efficient “on-demand” control of the motor output from the DMV in response to ever-changing demands required to maintain homeostasis. PMID:21147043

  6. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

    PubMed

    Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2014-04-10

    In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium.

    PubMed

    Kakinuma, Yoshihiko; Akiyama, Tsuyoshi; Sato, Takayuki

    2009-09-01

    Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti-Alzheimer's disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro. On the basis of this and evidence that vagal innervation is extremely poor in the left ventricle, we assessed the hypothesis that ACh is produced by cardiomyocytes, which promotes its synthesis via a positive feedback mechanism. Rat cardiomyocytes expressed choline acetyltransferase (ChAT) in the cytoplasm and vesicular acetylcholine transporter with the vesicular structure identified by immunogold electron microscopy, suggesting that cardiomyocytes possess components for ACh synthesis. Intracellular ACh in rat cardiomyocytes was identified with physostigmine or donepezil. However, with atropine, the basal ACh content was reduced. In response to exogenous ACh or pilocarpine, cardiomyocytes increased the transcriptional activity of the ChAT gene through a muscarinic receptor and ChAT protein expression, and, finally, the intracellular ACh level was upregulated by pilocarpine. Knockdown of ChAT by small interfering RNA accelerated cellular energy metabolism, which is suppressed by ACh. Although physostigmine had a minimal effect on the ChAT promoter activity by inhibiting acetylcholinesterase, donepezil resulted in elevation of the activity, protein expression and intracellular ACh level even in the presence of sufficient physostigmine. Orally administered donepezil in mice increased the ChAT promoter activity in a reporter gene-transferred quadriceps femoris muscle and the amount of cardiac ChAT protein. These findings suggest that cardiomyocytes possess an ACh synthesis system, which is positively modulated by cholinergic stimuli. Such an amplification system in cardiomyocytes may contribute to the beneficial effects of vagal stimulation on the ventricles.

  8. Heart Rate Variability and Cardiac Vagal Tone in Psychophysiological Research – Recommendations for Experiment Planning, Data Analysis, and Data Reporting

    PubMed Central

    Laborde, Sylvain; Mosley, Emma; Thayer, Julian F.

    2017-01-01

    Psychophysiological research integrating heart rate variability (HRV) has increased during the last two decades, particularly given the fact that HRV is able to index cardiac vagal tone. Cardiac vagal tone, which represents the contribution of the parasympathetic nervous system to cardiac regulation, is acknowledged to be linked with many phenomena relevant for psychophysiological research, including self-regulation at the cognitive, emotional, social, and health levels. The ease of HRV collection and measurement coupled with the fact it is relatively affordable, non-invasive and pain free makes it widely accessible to many researchers. This ease of access should not obscure the difficulty of interpretation of HRV findings that can be easily misconstrued, however, this can be controlled to some extent through correct methodological processes. Standards of measurement were developed two decades ago by a Task Force within HRV research, and recent reviews updated several aspects of the Task Force paper. However, many methodological aspects related to HRV in psychophysiological research have to be considered if one aims to be able to draw sound conclusions, which makes it difficult to interpret findings and to compare results across laboratories. Those methodological issues have mainly been discussed in separate outlets, making difficult to get a grasp on them, and thus this paper aims to address this issue. It will help to provide psychophysiological researchers with recommendations and practical advice concerning experimental designs, data analysis, and data reporting. This will ensure that researchers starting a project with HRV and cardiac vagal tone are well informed regarding methodological considerations in order for their findings to contribute to knowledge advancement in their field. PMID:28265249

  9. Synaptic potentials in respiratory neurones during evoked phase switching after NMDA receptor blockade in the cat

    PubMed Central

    Pierrefiche, O; Haji, A; Foutz, A S; Takeda, R; Champagnat, J; Denavit-Saubié, M

    1998-01-01

    Blockade of NMDA receptors by dizocilpine impairs the inspiratory off-switch (IOS) of central origin but not the IOS evoked by stimulation of sensory afferents. To investigate whether this difference was due to the effects of different patterns of synaptic interactions on respiratory neurones, we stimulated electrically the superior laryngeal nerve (SLN) or vagus nerve in decerebrate cats before and after i.v. administration of dizocilpine, whilst recording intracellularly. Phrenic nerve responses to ipsilateral SLN or vagal stimulation were: at mid-inspiration, a transient inhibition often followed by a brief burst of activity; at late inspiration, an IOS; and at mid-expiration, a late burst of activity. In all neurones (n = 16), SLN stimulation at mid-inspiration evoked an early EPSP during phase 1 (latency to the arrest of phrenic nerve activity), followed by an IPSP in inspiratory (I) neurones (n = 8) and by a wave of EPSPs in post-inspiratory (PI) neurones (n = 8) during phase 2 (inhibition of phrenic activity). An EPSP in I neurones and an IPSP in PI neurones occurred during phase 3 (brief phrenic burst) following phase 2. Evoked IOS was associated with a fast (phase 1) activation of PI neurones, whereas during spontaneous IOS, a progressive (30-50 ms) depolarization of PI neurones preceded the arrest of phrenic activity. Phase 3 PSPs were similar to those occurring during the burst of activity seen at the start of spontaneous inspiration. Dizocilpine did not suppress the evoked phrenic inhibition and the late burst of activity. The shapes and timing of the evoked PSPs and the changes in membrane potential in I and PI neurones during the phase transition were not altered. We hypothesize that afferent sensory pathways not requiring NMDA receptors (1) terminate inspiration through a premature activation of PI neurones, and (2) evoke a late burst of phrenic activity which might be the first stage of the inspiratory on-switch. PMID:9508816

  10. Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium

    PubMed Central

    Hoover, Donald B.; Shepherd, Angela V.; Southerland, E. Marie; Armour, J. Andrew; Ardell, Jeffrey L.

    2008-01-01

    While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T3 DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T3 DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30–40% of ventricular afferent somata in T3 DRG). About 30% of the ventricular afferent neurons in T2 DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB4. Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters. PMID:18558516

  11. Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium.

    PubMed

    Hoover, Donald B; Shepherd, Angela V; Southerland, E Marie; Armour, J Andrew; Ardell, Jeffrey L

    2008-08-18

    While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T(3) DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T(3) DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30-40% of ventricular afferent somata in T(3) DRG). About 30% of the ventricular afferent neurons in T(2) DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB(4). Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters.

  12. Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

    PubMed

    Baral, Pankaj; Umans, Benjamin D; Li, Lu; Wallrapp, Antonia; Bist, Meghna; Kirschbaum, Talia; Wei, Yibing; Zhou, Yan; Kuchroo, Vijay K; Burkett, Patrick R; Yipp, Bryan G; Liberles, Stephen D; Chiu, Isaac M

    2018-05-01

    Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1 + nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1 + -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1 + afferents mediated immunosuppression through release of the neuropeptide calcitonin gene-related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.

  13. Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin.

    PubMed

    Grabauskas, Gintautas; Moises, Hylan C

    2003-05-15

    Orexin (hypocretin)-containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration of orexin peptides increases food intake, and orexin neurones in the LH are activated by hypoglycaemia during fasting. In addition, administration of orexins into the fourth ventricle or the dorsal motor nucleus of the vagus (DMV) has been shown to stimulate gastric acid secretion and motility, respectively, via vagal efferent pathways. In this study, whole-cell recordings were obtained from DMV neurones in rat brainstem slices to investigate the cellular mechanism(s) by which orexins produce their gastrostimulatory effects. To determine whether responsiveness to orexins might be differentially expressed among distinct populations of preganglionic vagal motor neurones, recordings were made from neurones whose projections to the gastrointestinal tract had been identified by retrograde labelling following apposition of the fluorescent tracer DiI to the gastric fundus, corpus or antrum/pylorus, the duodenum or caecum. Additionally, the responses of neurones to orexins were compared with those produced by oxytocin, which acts within the DMV to stimulate gastric acid secretion, but inhibits gastric motor function. Bath application of orexin-A or orexin-B (30-300 nM) produced a slow depolarization, accompanied by increased firing in 47 of 102 DMV neurones tested, including 70 % (30/43) of those that projected to the gastric fundus or corpus. In contrast, few DMV neurones that supplied the antrum/pylorus (3/13), duodenum (4/18) or caecum (1/13) were responsive to these peptides. The depolarizing responses were concentration dependent and persisted during synaptic isolation of neurones with TTX or Cd2+, indicating they resulted from activation of postsynaptic orexin receptors. They were also associated with a small increase in membrane resistance, and in voltage

  14. Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin

    PubMed Central

    Grabauskas, Gintautas; Moises, Hylan C

    2003-01-01

    Orexin (hypocretin)-containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration of orexin peptides increases food intake, and orexin neurones in the LH are activated by hypoglycaemia during fasting. In addition, administration of orexins into the fourth ventricle or the dorsal motor nucleus of the vagus (DMV) has been shown to stimulate gastric acid secretion and motility, respectively, via vagal efferent pathways. In this study, whole-cell recordings were obtained from DMV neurones in rat brainstem slices to investigate the cellular mechanism(s) by which orexins produce their gastrostimulatory effects. To determine whether responsiveness to orexins might be differentially expressed among distinct populations of preganglionic vagal motor neurones, recordings were made from neurones whose projections to the gastrointestinal tract had been identified by retrograde labelling following apposition of the fluorescent tracer DiI to the gastric fundus, corpus or antrum/pylorus, the duodenum or caecum. Additionally, the responses of neurones to orexins were compared with those produced by oxytocin, which acts within the DMV to stimulate gastric acid secretion, but inhibits gastric motor function. Bath application of orexin-A or orexin-B (30–300 nm) produced a slow depolarization, accompanied by increased firing in 47 of 102 DMV neurones tested, including 70 % (30/43) of those that projected to the gastric fundus or corpus. In contrast, few DMV neurones that supplied the antrum/pylorus (3/13), duodenum (4/18) or caecum (1/13) were responsive to these peptides. The depolarizing responses were concentration dependent and persisted during synaptic isolation of neurones with TTX or Cd2+, indicating they resulted from activation of postsynaptic orexin receptors. They were also associated with a small increase in membrane resistance, and in voltage

  15. [Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

    PubMed

    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.

  16. The Heart´s rhythm 'n' blues: Sex differences in circadian variation patterns of vagal activity vary by depressive symptoms in predominantly healthy employees.

    PubMed

    Jarczok, Marc N; Aguilar-Raab, Corina; Koenig, Julian; Kaess, Michael; Borniger, Jeremy C; Nelson, Randy J; Hall, Martica; Ditzen, Beate; Thayer, Julian F; Fischer, Joachim E

    2018-03-15

    Successful regulation of emotional states is positively associated to mental health, while difficulties in regulating emotions are negatively associated to overall mental health and in particular associated with anxiety or depression symptoms. A key structure associated to socio-emotional regulatory processes is the central autonomic network. Activity in this structure is associated to vagal activity can be indexed noninvasively and simply by measures of peripheral cardiac autonomic modulations such as heart rate variability. Vagal activity exhibits a circadian variation pattern, with a maximum during nighttime. Depression is known to affect chronobiology. Also, depressive symptoms are known to be associated with decreased resting state vagal activity, but studies investigating the association between circadian variation pattern of vagal activity and depressive symptoms are scarce. We aim to examine these patterns in association to symptom severity of depression using chronobiologic methods. Data from the Manheim Industrial Cohort Studies (MICS) were used. A total of 3,030 predominantly healthy working adults underwent, among others, ambulatory 24-h hear rate-recordings, detailed health examination and online questionnaires and were available for this analysis. The root mean sum of successive differences (RMSSD) was used as an indicator of vagally mediated heart rate variability. Three individual-level cosine function parameters (MESOR, amplitude, acrophase) were estimated to quantify circadian variation pattern. Multivariate linear regression models including important covariates such as age, sex, and lifestyle factors as well as an interaction effect of sex with depressive symptoms were used to estimate the association of circadian variation pattern of vagal activity with depressive symptoms simultaneously. The analysis sample consisted of 20.2% females and an average age 41 with standard deviation of 11 years. Nonparametric bivariate analysis revealed

  17. Sodium intake and cardiac sympatho-vagal balance in young men with high blood pressure.

    PubMed

    Tochikubo, Osamu; Nishijima, Kiyoko

    2004-06-01

    We have previously reported that a high sodium intake increases sleep-time blood pressure (BP) in young men. However, there are cases in which this relation does not apply. To account for them, we investigated the relation between sodium intake and cardiac sympatho-vagal balance (SVB) in young men with high BP. Sodium intake was estimated from the amount of urinary sodium excretion over 1 week. Twenty-four-hour (24-h) urinary sodium excretion (Salt24), 24-h ambulatory BP and ECG were obtained on the last day of the observation period. As an index of sodium intake, the expression In(Salt24/Cr24) (Cr24, 24-h urinary creatinine excretion) was used. From power-spectral analysis of ECG-RR intervals during sleep, we obtained the LF/HF ratio between the low-frequency component (LF) and the high frequency component (HF) and used it as an index of SVB. The subjects were male medical students divided into a normal BP group (N-group; n=103) and a high BP group (H-group; n=26, 24-h BP>125/75 mmHg). Mean In(Salt24/Cr24) and LF/HF in the H-group were significantly higher than those in the N-group (LF/HF: 1.86+/-0.44 [SD] vs. 1.37+/-0.30, p<0.001). The calculated discriminant function (D) for the H-group and N-group was D=1.6x + 5y - 11, where x is In(Salt24/Cr24) and y is LF/HF. This formula (D) resulted in high discriminant predictive accuracy (82%) between the groups. If D=0 (the value of the cut-off line determining separation of the groups), the relation y=-0.32x + 2.2 (negative relation between y and x) was obtained. These results suggest that excessive sodium intake in combination with accentuated SVB (LF/HF) increases BP in young men.

  18. Suppression of vagal cardiac modulation by blue light in healthy subjects.

    PubMed

    Yuda, Emi; Ogasawara, Hiroki; Yoshida, Yutaka; Hayano, Junichiro

    2016-10-05

    In the contemporary life environments, our body is increasingly exposed to various sources of colored light, which may affect our physiological functions as non-image-forming effects. We examined the impacts of colored lights on the autonomic functions by the analysis of heart rate variability (HRV). A lighting device consisting of four organic light-emitting diode (OLED) modules (55 × 55 mm 2 ) with adjustable red-green-blue color was secured 24 cm above the eyes of subject lying supine in a light-shielded laboratory. Following a 15-min supine rest, electrocardiogram and respiration were measured continuously during 3-min darkness, 6-min colored OLED illumination, and 3-min darkness under paced breathing (15 breath/min). The measurements were repeated at a 45-min interval for red, green, and blue lights with melanopsin-stimulating photon flux density (MSPFD) of 0.00, 0.10, and 0.20 μmol/m 2 /s, respectively, in 12 healthy subjects (23 ± 2 years, two females). Additionally, the effects of blue lights with 0.20, 0.10, and 0.04 μmol/m 2 /s MSPFD were examined in four healthy subjects (25-39 years, two females). HRV was analyzed for low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.20-0.30 Hz) power and LF-to-HF ratio (LF/HF). Compared to darkness before lighting, HF power decreased (P < 0.001) and LF/HF increased (P = 0.024) during lighting on average of all color lights, whereas HF power showed a greater decrease with blue light than with red and green lights (P < 0.05 for both). The decrease in HF power lasted even during darkness after lighting (P < 0.001). HF power decreased with blue light with 0.20 μmol/m 2 /s MSPFD (P < 0.001) but not with that with 0.10 or 0.04 μmol/m 2 /s (P = 0.1 and 0.9, respectively). Vagal cardiac modulation is suppressed by OLED blue light in healthy subjects most likely through melanopsin-dependent non-image-forming effect.

  19. The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics.

    PubMed

    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 β 1 -adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE 1-5 ) and long (6 to 30, MSE 6-30 ) time scales was computed, as well as DFA scaling exponents at short (α short , 5 ≤ n ≤ 15), mid (α mid , 30 ≤ n ≤ 200), and long (α long , 200 ≤ n ≤ 1,700) window sizes. The results show that MSE 1-5 is reduced under atropine blockade and MSE 6-30 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, α short decreased during atenolol blockade, while the α mid increased under atropine blockade. Double blockade decreased α short and increased α long 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

  20. Vagal nerve stimulation modulates the dendritic cell profile in posthemorrhagic shock mesenteric lymph.

    PubMed

    Morishita, Koji; Costantini, Todd W; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul

    2014-03-01

    Previous studies have established that posthemorrhagic shock mesenteric lymph (PHSML) contains proinflammatory mediators, while the cellular basis of PHSML is less well characterized in acute models of injury. CD103 dendritic cells (DCs) have been identified in the mesenteric lymph (ML) in models of chronic intestinal inflammation, suggesting an important role in the gut response to injury. We have previously demonstrated the ability of vagal nerve stimulation (VNS) to prevent gut barrier failure after trauma/hemorrhagic shock (T/HS); however, the ability of VNS to alter ML DCs is unknown. We hypothesized that the CD103 MHC-II DC population would change in PHSML and that VNS would prevent injury-induced changes in this population in PHSML. Male Sprague-Dawley rats were randomly assigned to trauma/sham shock or T/HS. T/HS was induced by midline laparotomy and 60 minutes of HS (blood pressure, 35 mm Hg), followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. Gut tissue was harvested at 2 hours after injury for histologic analysis. ML was collected during the pre-HS, HS, and post-HS phase. For flow cytometric analysis, ML cells were subjected to staining with CD103 and MHC-II antibodies, and this cell population was compared in the pre-HS and post-HS phase from the same animal. The CD4Foxp3 cell (T reg) population in the ML node (MLN) was also tested to determine effects of CD103 DC modulation in the ML. VNS reduced histologic gut injury and ML flow seen after injury. The CD103 MHC-II DC population in the PHSML was significantly decreased compared with pre-HS and was associated with decreased T reg expression in the MLN. VNS prevented the injury-induced decrease in the CD103 MHC-II+ DC population in the ML and restored the T reg population in the MLN. These findings suggest that VNS mediates the inflammatory responses in ML DCs and MLN T reg cells by affecting the set point of T/HS responsiveness.

  1. The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective.

    PubMed

    Al Omari, Ahmad I; Alzoubi, Firas Q; Alsalem, Mohammad M; Aburahma, Samah K; Mardini, Diala T; Castellanos, Paul F

    Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years. VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively. This study is to review the outcomes of vagal nerve stimulator (VNS) implantation in terms of the surgical procedures, complications, seizure frequency, and the clinical effect on larynx and vocal folds motion. Series of thirty consecutive patients who had VNS implantation between 2007 and 2014 were recruited. Seizure-frequency outcome, surgical complications and device adverse effects of VNS were retrospectively reviewed. Additional evaluation included use of the Voice Handicap Index and Maximum Phonation Time (MPT) were conducted before and after the implantation. Videolaryngoscopy was used to evaluate the vocal fold mobility before and after the VNS implantation. Seizure frequency reduction over a minimum of 2years of follow up demonstrated: 100% in seizure frequency reduction in 1 patient, drastic reduction in seizure frequency (70-90%) in 9 patients, a good reduction in terms of seizure frequency (50%) in 8 patients, a 30% reduction in 5 patients, no response in 6 patients, and 1 patient had increased frequency. The most commonly reported adverse effects after VNS activation were coughing and voice changes with pitch breaks, as well as mild intermittent shortness of breath in 33% of patients. For those patients secondary supraglottic muscle tension and hyper function with reduced left vocal fold mobility were noticed on videolaryngoscopy, though none had aspiration problems. Surgical complications included a wound dehiscence in one patient (3%) which was surgically managed, minor intra-operative bleeding 3%; a

  2. Mother-infant dyadic reparation and individual differences in vagal tone affect 4-month-old infants' social stress regulation.

    PubMed

    Provenzi, Livio; Casini, Erica; de Simone, Paola; Reni, Gianluigi; Borgatti, Renato; Montirosso, Rosario

    2015-12-01

    Infants' social stress regulation (i.e., reactivity and recovery) might be affected by mother-infant dyadic functioning and infants' vagal tone (i.e., respiratory sinus arrhythmia, RSA). This study investigated the role of a specific dyadic functioning feature (i.e., dyadic reparation) and individual differences in vagal tone regulation (i.e., RSA suppression vs. non-suppression) in relation to social stress regulation in 4-month-old infants. A total of 65 mother-infant dyads participated in the face-to-face still-face paradigm. Social stress reactivity and recovery were measured as negative emotionality during Still-Face and Reunion episodes, respectively. RSA was measured during Play, Still-Face, and Reunion episodes. Suppressors had higher dyadic reparation during Play and higher recovery from social stress compared with non-suppressors. Higher reparation during Play was associated with lower reactivity and higher recovery only for suppressors. Findings suggest a joint role of infants' RSA individual differences and dyadic reparation in affecting infants' social stress regulation at 4 months of age. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

    PubMed

    Mounien, Lourdes; Marty, Nell; Tarussio, David; Metref, Salima; Genoux, David; Preitner, Frédéric; Foretz, Marc; Thorens, Bernard

    2010-06-01

    The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.

  4. Motor Neuron Diseases

    MedlinePlus

    ... length SMN protein, which is critical for the maintenance of motor neurons. Physical and speech therapy, occupational ... length SMN protein, which is critical for the maintenance of motor neurons. Physical and speech therapy, occupational ...

  5. Infant diet sets the tone for parasympathetic regulation of resting heart rate: Development of vagal tone from 3 months to 2 years

    The parasympathetic nervous system (PS) influences are critical in the autonomic control of the heart. To examine how early postnatal diet affects PS development, we used a measure of tonic PS control of cardiac activity, vagal tone, derived from resting heart rate recordings in 158 breastfed (BF), ...

  6. Heightened Vagal Activity during High-Calorie Food Presentation in Obese compared with Non-obese Individuals - Results of a Pilot Study

    PubMed Central

    Udo, Tomoko; Weinberger, Andrea H.; Grilo, Carlos M.; Brownell, Kelly D.; DiLeone, Ralph J.; Lampert, Rachel; Matlin, Samantha L.; Yanagisawa, Katherine; McKee, Sherry A.

    2013-01-01

    Summary Eating behaviors 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 behaviors. 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 < BMI < 30). Participants completed two laboratory sessions (negative vs. positive mood conditions). Following 3-hours 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 of vagally-mediated cue reactivity in overeating and obesity. PMID:24847667

  7. Reduced N-Type Ca2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis.

    PubMed

    Zhang, Dongze; Tu, Huiyin; Cao, Liang; Zheng, Hong; Muelleman, Robert L; Wadman, Michael C; Li, Yu-Long

    2018-01-15

    Attenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N-type Ca 2+ channel α-subunits (Ca v 2.2-α) and N-type Ca 2+ currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the AVG. In this study we tested whether a decrease in N-type Ca 2+ channels in AVG neurons contributes to ventricular arrhythmogenesis. Lentiviral Ca v 2.2-α shRNA (2 μL, 2×10 7  pfu/mL) or scrambled shRNA was in vivo transfected into rat AVG neurons. Nontransfected sham rats served as controls. Using real-time single-cell polymerase chain reaction and reverse-phase protein array, we found that in vivo transfection of Ca v 2.2-α shRNA decreased expression of Ca v 2.2-α mRNA and protein in rat AVG neurons. Whole-cell patch-clamp data showed that Ca v 2.2-α shRNA reduced N-type Ca 2+ currents and cell excitability in AVG neurons. The data from telemetry electrocardiographic recording demonstrated that 83% (5 out of 6) of conscious rats with Ca v 2.2-α shRNA transfection had premature ventricular contractions ( P <0.05 versus 0% of nontransfected sham rats or scrambled shRNA-transfected rats). Additionally, an index of susceptibility to ventricular arrhythmias, inducibility of ventricular arrhythmias evoked by programmed electrical stimulation, was higher in rats with Ca v 2.2-α shRNA transfection compared with nontransfected sham rats and scrambled shRNA-transfected rats. A decrease in N-type Ca 2+ channels in AVG neurons attenuates vagal control of ventricular myocardium, thereby initiating ventricular arrhythmias. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. The oesophagus and cough: laryngo-pharyngeal reflux, microaspiration and vagal reflexes

    PubMed Central

    2013-01-01

    Gastro-oesophageal reflux disease is generally considered to be one of the commonest causes of chronic cough, however randomised controlled trials of proton pump inhibitors have often failed to support this notion. This article reviews the most recent studies investigating the mechanisms thought to link reflux and cough, namely laryngo-pharyngeal reflux, micro-aspiration and neuronal cross-organ sensitisation. How recent evidence might shed light on the failure of acid suppressing therapies and suggest new approaches to treating reflux related cough are also discussed. PMID:23590893

  9. Concurrent sympathetic activation and vagal withdrawal in hyperthyroidism: Evidence from detrended fluctuation analysis of heart rate variability

    NASA Astrophysics Data System (ADS)

    Chen, Jin-Long; Shiau, Yuo-Hsien; Tseng, Yin-Jiun; Chiu, Hung-Wen; Hsiao, Tzu-Chien; Wessel, Niels; Kurths, Jürgen; Chu, Woei-Chyn

    2010-05-01

    Despite many previous studies on the association between hyperthyroidism and the hyperadrenergic state, controversies still exist. Detrended fluctuation analysis (DFA) is a well recognized method in the nonlinear analysis of heart rate variability (HRV), and it has physiological significance related to the autonomic nervous system. In particular, an increased short-term scaling exponent α1 calculated from DFA is associated with both increased sympathetic activity and decreased vagal activity. No study has investigated the DFA of HRV in hyperthyroidism. This study was designed to assess the sympathovagal balance in hyperthyroidism. We performed the DFA along with the linear analysis of HRV in 36 hyperthyroid Graves’ disease patients (32 females and 4 males; age 30 ± 1 years, means ± SE) and 36 normal controls matched by sex, age and body mass index. Compared with the normal controls, the hyperthyroid patients revealed a significant increase ( P<0.001) in α1 (hyperthyroid 1.28±0.04 versus control 0.91±0.02), long-term scaling exponent α2 (1.05±0.02 versus 0.90±0.01), overall scaling exponent α (1.11±0.02 versus 0.89±0.01), low frequency power in normalized units (LF%) and the ratio of low frequency power to high frequency power (LF/HF); and a significant decrease ( P<0.001) in the standard deviation of the R-R intervals (SDNN) and high frequency power (HF). In conclusion, hyperthyroidism is characterized by concurrent sympathetic activation and vagal withdrawal. This sympathovagal imbalance state in hyperthyroidism helps to explain the higher prevalence of atrial fibrillation and exercise intolerance among hyperthyroid patients.

  10. Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication.

    PubMed

    Gierthmuehlen, Mortimer; Plachta, Dennis T T

    2016-02-01

    Selective vagal nerve stimulation (sVNS) has been shown to reduce blood pressure without major side effects in rats. This technology might be the key to non-medical antihypertensive treatment in patients with therapy-resistant hypertension. β-blockers are the first-line therapy of hypertension and have in general a bradycardic effect. As VNS itself can also promote bradycardia, it was the aim of this study to investigate the influence of the β1-selective blocker Metoprolol on the effect of sVNS especially with respect to the heart rate. In 10 male Wistar rats, a polyimide multichannel-cuff electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibers. The stimulation parameters were adapted to the thresholds of individual animals and were in the following ranges: frequency 30-50 Hz, amplitude 0.3-1.8 mA and pulse width 0.3-1.3 ms. Blood pressure responses were detected with a microtip transducer in the carotid artery, and electrocardiography was recorded with s.c. chest electrodes. After IV administration of Metoprolol (2 mg kg(-1) body weight), the animals' mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly. Although the selective electrical stimulation of the baroreceptive fibers reduced MAP and HR, both effects were significantly alleviated by Metoprolol. As a side effect, the rate of stimulation-induced apnea significantly increased after Metoprolol administration. sVNS can lower the MAP under Metoprolol without causing severe bradycardia.

  11. Hypothesis that vagal reinervation of diaphragm could sensitise it to electrical stimulation.

    PubMed

    Pavlovic, Dragan; Wendt, Michael

    2003-03-01

    The hypothesis proposed is that restoration of functional capacity of denervated diaphragm may be achieved by reinervating it with vagus nerve. Following trauma, carcinomatose infiltration, and/or large thoracic surgery and neck surgery, phrenic nerve is frequently injured. Reinervation even in the most favourable conditions would not follow and diaphragm would rest permanently denervated and paralysed. This results in unilateral or bilateral paralysis of diaphragm. In principle, intermittent electrical stimulation of the phrenic nerve or diaphragm could elicit regular diaphragm contractions and maintain satisfactory respiration. While this technique could be used in upper motor neurone injury, in lower motor neurone injury and denervated diaphragm, that imposes too high electrical resistance, direct diaphragm pacing is practically impossible. In these cases, long term artificial ventilation is often necessary. Nevertheless, those patients are at high risk to suffer from atelectasis and respiratory infections. We project a hypothesis that reinervation of denervated diaphragm by vagus nerve could re-establishes its sensitivity to intramuscular electrical stimulation and may allow stimulation of the diaphragm by implanted pace-maker electrodes. An appropriate electrical stimulation might then be possible and diaphragm pacing could replace prolonged artificial ventilation in those patients. Restoration of functional capacity of denervated diaphragm could open a perspective for long term diaphragm pacing in patients with irreversible phrenic nerve injury and diaphragm paralysis.

  12. Neuronal Mechanisms of Intelligence.

    DTIC Science & Technology

    1984-11-01

    integrated activity of neuronal ircuits, that is -~ directly modified by reinforcing signals. -S. a -4 ’ p ...kinds of consequences and a supply of behavior ... which has little or no relation to (eliciting or releasing) stimuli." ( p . 501). As a consequence, the...fraction of these synapses is active" ( p . 5). Klopf’s heterostat is diagrammed as a 3-neuron assembly in Fig. 1, which shows a "reinforced" neuron and its

  13. Neurofibromin and Neuronal Apoptosis

    DTIC Science & Technology

    2006-07-01

    role of familial pheochromocytoma genes, including succinate dehydrogenase (SDH) and Nf1, in modulating neuronal apoptosis following neurotrophin...gene products, in Nf1-/- sensory and sympathetic neurons; this work will also have relevance to the biology of familial pheochromocytoma . "So what...Schlisio, S. (2005). Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: Developmental culling and cancer. Cancer

  14. Foot reflexology can increase vagal modulation, decrease sympathetic modulation, and lower blood pressure in healthy subjects and patients with coronary artery disease.

    PubMed

    Lu, Wan-An; Chen, Gau-Yang; Kuo, Cheng-Deng

    2011-01-01

    Complementary and alternative medicine (CAM) has long been used by people to postpone the aging process and to reverse disease progression. Reflexology is a CAM method that involves massage to reflex areas in the feet and hands. This study investigated the effect of foot reflexology (FR) on the autonomic nervous modulation in patients with coronary artery disease (CAD) by using heart rate variability analysis. Seventeen people with angiographically patent coronary arteries and 20 patients with CAD scheduled for coronary artery bypass graft surgery were recruited as the control and CAD groups, respectively. The normalized high-frequency power (nHFP) was used as the index of vagal modulation and the normalized very low-frequency power (nVLFP) as the index of vagal withdrawal and renin-angiotensin modulation. In both control and CAD groups, the nHFP was increased significantly whereas the nVLFP was decreased significantly 30 and 60 minutes after FR, as compared with those before FR. The systolic, diastolic, mean arterial, and pulse pressures were significantly decreased after FR in both groups of participants. In the CAD group, the percentage change in heart rate 30 and 60 minutes after FR was smaller than that in the control, and the percentage change in nVLFP 60 minutes after FR was smaller than that in the control. In conclusion, a higher vagal modulation, lower sympathetic modulation, and lower blood pressure can be observed following 60 minutes of FR in both controls and CAD patients. The magnitude of change in the autonomic nervous modulation in CAD patients was slightly smaller than that in the controls. FR may be used as an efficient adjunct to the therapeutic regimen to increase the vagal modulation and decrease blood pressure in both healthy people and CAD patients.

  15. Ventricular tachyarrhythmia-related basal cardiomyopathy in rabbits with vagal stimulation--a novel experimental model for inverted Takotsubo-like cardiomyopathy.

    PubMed

    Takato, Tetsuya; Ashida, Terunao; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

    2010-07-01

    Electrical stimulation of the intact (unsectioned) cervical vagus in rabbits frequently provokes ventricular tachyarrhythmias that are often accompanied by mitral regurgitation. Unique pathological lesions often arise on the mitral valve, papillary muscles, and mitral annulus (mitral complex), the latter two of which become swollen and stiffened. These lesions are reversible in nature. Previous studies have essentially ignored the basal portion except for the mitral annulus. Therefore, the present study examined pathological lesions on the left ventricular basal portion in rabbits. The intact right vagal nerves of 20 anesthetized rabbits were repeatedly electrically stimulated under electrocardiographic monitoring. Colloidal carbon (lml) was injected intravenously immediately after the end of the stimulation and all animals were killed 1 week later. Pathological lesions were identified as carbon deposits visible at gross examination. Ventricular bigeminy was induced after vagal stimulation in 15 (75%) of the 20 rabbits. Pathological lesions were evident on the basal portion in 16 (80%) and on the mitral valve and papillary muscles of 15 (75%) of the 20 rabbits. Ventricular bigeminy was closely associated with the development of the pathological lesions, which were rarely observed on the ventricular apex. Cardiomyopathic lesions involving the basal portion and mitral complex were frequently induced in rabbits by vagal stimulation. These lesions bear a close similarity in distribution and reversibility to inverted Takotsubo cardiomyopathy. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  16. Individual differences in cardiac vagal tone are associated with differential neural responses to facial expressions at different spatial frequencies: an ERP and sLORETA study.

    PubMed

    Park, Gewnhi; Moon, Eunok; Kim, Do-Won; Lee, Seung-Hwan

    2012-12-01

    A previous study has shown that greater cardiac vagal tone, reflecting effective self-regulatory capacity, was correlated with superior visual discrimination of fearful faces at high spatial frequency Park et al. (Biological Psychology 90:171-178, 2012b). The present study investigated whether individual differences in cardiac vagal tone (indexed by heart rate variability) were associated with different event-related brain potentials (ERPs) in response to fearful and neutral faces. Thirty-six healthy participants discriminated the emotion of fearful and neutral faces at broad, high, and low spatial frequencies, while ERPs were recorded. Participants with low resting heart rate variability-characterized by poor functioning of regulatory systems-exhibited significantly greater N200 activity in response to fearful faces at low spatial frequency and greater LPP responses to neutral faces at high spatial frequency. Source analyses-estimated by standardized low-resolution brain electromagnetic tomography (sLORETA)-tended to show that participants with low resting heart rate variability exhibited increased source activity in visual areas, such as the cuneus and the middle occipital gyrus, as compared with participants with high resting heart rate variability. The hyperactive neural activity associated with low cardiac vagal tone may account for hypervigilant response patterns and emotional dysregulation, which heightens the risk of developing physical and emotional problems.

  17. High-Resolution Manometry Evaluation of Pressures at the Pharyngo-upper Esophageal Area in Patients with Oropharyngeal Dysphagia Due to Vagal Paralysis.

    PubMed

    Pinna, Bruno Rezende; Herbella, Fernando A M; de Biase, Noemi; Vaiano, Thays C G; Patti, Marco G

    2017-10-01

    The motility of the pharynx, upper esophageal sphincter (UES), and proximal esophagus in patients with oropharyngeal dysphagia is still not entirely understood. High-resolution manometry (HRM) was recently added to the armamentarium for the study of this area. This study aims to describe HRM findings in patients with vagal paralysis. Sixteen patients (mean age 54 years, 69% females) with oropharyngeal dysphagia due to unilateral vagal paralysis were prospectively studied. All patients underwent HRM. Motility of the UES and at the topography of the velopharynx and epiglottis were recorded. (1) UES relaxation is compromised in a minority of patients, (2) epiglottis pressure does not follow a specific pattern, (3) vellum is hypotonic in half of the patients, (4) dysphagia is related to a low pharyngeal pressure, not to a flow obstruction at the level of the UES, and (5) aspiration is related to low pressures at the level of the UES and epiglottis and higher pressures at the level of the vellum. Pharyngeal motility is significantly impaired in patients with oropharyngeal dysphagia and unilateral vagal paralysis. In half of the cases, UES resting pressure is preserved due to unilateral innervation and relaxation is normal in most patients. Dysphagia therapy in these patients must be directed toward improvement in the oropharyngeal motility not at the UES.

  18. How positive emotions build physical health: perceived positive social connections account for the upward spiral between positive emotions and vagal tone.

    PubMed

    Kok, Bethany E; Coffey, Kimberly A; Cohn, Michael A; Catalino, Lahnna I; Vacharkulksemsuk, Tanya; Algoe, Sara B; Brantley, Mary; Fredrickson, Barbara L

    2013-07-01

    The mechanisms underlying the association between positive emotions and physical health remain a mystery. We hypothesize that an upward-spiral dynamic continually reinforces the tie between positive emotions and physical health and that this spiral is mediated by people's perceptions of their positive social connections. We tested this overarching hypothesis in a longitudinal field experiment in which participants were randomly assigned to an intervention group that self-generated positive emotions via loving-kindness meditation or to a waiting-list control group. Participants in the intervention group increased in positive emotions relative to those in the control group, an effect moderated by baseline vagal tone, a proxy index of physical health. Increased positive emotions, in turn, produced increases in vagal tone, an effect mediated by increased perceptions of social connections. This experimental evidence identifies one mechanism-perceptions of social connections-through which positive emotions build physical health, indexed as vagal tone. Results suggest that positive emotions, positive social connections, and physical health influence one another in a self-sustaining upward-spiral dynamic.

  19. Physiological correlates of memory recall in infancy: vagal tone, cortisol, and imitation in preterm and full-term infants at 6 months.

    PubMed

    Haley, David W; Grunau, Ruth E; Weinberg, Joanne; Keidar, Adi; Oberlander, Tim F

    2010-04-01

    We examined the role of physiological regulation (heart rate, vagal tone, and salivary cortisol) in short-term memory in preterm and full-term 6-month-old infants. Using a deferred imitation task to evaluate social learning and memory recall, an experimenter modeled three novel behaviors (removing, shaking, and replacing a glove) on a puppet. Infants were tested immediately after being shown the behaviors as well as following a 10-min delay. We found that greater suppression of vagal tone was related to better memory recall in full-term infants tested immediately after the demonstration as well as in preterm infants tested later after a 10-min delay. We also found that preterm infants showed greater coordination of physiology (i.e., tighter coupling of vagal tone, heart rate, and cortisol) at rest and during retrieval than full-term infants. These findings provide new evidence of the important links between changes in autonomic activity and memory recall in infancy. They also raise the intriguing possibility that social learning, imitation behavior, and the formation of new memories are modulated by autonomic activity that is coordinated differently in preterm and full-term infants. Copyright 2009 Elsevier Inc. All rights reserved.

  20. Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism.

    PubMed

    Shin, Andrew C; Zheng, Huiyuan; Berthoud, Hans-Rudolf

    2012-02-01

    To determine the role of the common hepatic branch of the abdominal vagus on the beneficial effects of Roux-en-Y gastric bypass (RYGB) on weight loss, food intake, food choice, and energy expenditure in a rat model. Although changes in gut hormone patterns are the leading candidates in RYGB's effects on appetite, weight loss, and reversal of diabetes, a potential role for afferent signaling through the vagal hepatic branch potentially sensing glucose levels in the hepatic portal vein has recently been suggested in a mouse model of RYGB. Male Sprague-Dawley rats underwent either RYGB alone (RYGB; n = 7), RYGB + common hepatic branch vagotomy (RYGB + HV; n = 6), or sham procedure (sham; n = 9). Body weight, body composition, meal patterns, food choice, energy expenditure, and fecal energy loss were monitored up to 3 months after intervention. Both RYGB and RYGB + HV significantly reduced body weight, adiposity, meal size, and fat preference, and increased satiety, energy expenditure, and respiratory exchange rate compared with sham procedure, and there were no significant differences in these effects between RYGB and RYGB + HV rats. Integrity of vagal nerve supply to the liver, hepatic portal vein, and the proximal duodenum provided by the common hepatic branch is not necessary for RYGB to reduce food intake and body weight or increase energy expenditure. Specifically, it is unlikely that a hepatic portal vein glucose sensor signaling RYGB-induced increased intestinal gluconeogenesis to the brain depends on vagal afferent fibers.

  1. Neuropeptide Y is a prejunctional inhibitor of vagal but not sympathetic inotropic responses in guinea-pig isolated left atria

    PubMed Central

    Serone, Adrian P; Angus, James A

    1999-01-01

    The effects of NPY and related peptides were examined on basal contractile force and nerve-mediated inotropic responses to electrical field stimulation of the guinea-pig isolated left atrium.Electrical field stimulus (EFS)-inotropic response curves were constructed by applying 1-64 trains of four field pulses (200 Hz, 0.1 ms duration, 100 V) across isolated left atria (paced at 4 Hz, 2 ms, 1–4 V) within the atrial refractory period. Curves were constructed in presence of vehicle, propranolol (1 μM) or atropine (1 μM) to determine appropriate stimulus conditions.The effects of PYY (1–10,000 nM), NPY (0.01–10 μM), N-Ac-[Leu28,31]NPY(24–36) (N-A[L]NPY(24–36); 0.01–10 μM) and clonidine (0.1–1000 nM) were examined on the positive and negative inotropic responses to EFS (eight trains, four pulses per refractory period).NPY-related peptides had no effect on basal force of contraction nor on the inotropic concentration-response curves to bethanechol or isoprenaline. All three peptides inhibited vagally-mediated negative inotropic responses; rank order of potency PYY>NPY⩾N-A[L]NPY(24–36) was consistent with an action at prejunctional Y2-receptors. Clonidine concentration-dependently inhibited sympathetic inotropic responses. However, PYY, NPY and N-A[L]NPY(24–36) failed to mediate any significant inhibition of the positive inotropic response to EFS.These data demonstrate that NPY is an effective inhibitor of vagal but not sympathetically-mediated inotropic responses in the guinea-pig isolated left atria. This may suggest that endogenously co-released NPY is important in mediating cross talk between efferent components of the autonomic nervous system modulating cardiac contractility, acting overall to sustain positive inotropic responses. PMID:10385237

  2. Evidence for glutamatergic mechanisms in the vagal sensory pathway initiating cardiorespiratory reflexes in the shorthorn sculpin Myoxocephalus scorpius.

    PubMed

    Sundin, L; Turesson, J; Taylor, E W

    2003-03-01

    Glutamate is a major neurotransmitter of chemoreceptor and baroreceptor afferent pathways in mammals and therefore plays a central role in the development of cardiorespiratory reflexes. In fish, the gills are the major sites of these receptors, and, consequently, the terminal field (sensory area) of their afferents (glossopharyngus and vagus) in the medulla must be an important site for the integration of chemoreceptor and baroreceptor signals. This investigation explored whether fish have glutamatergic mechanisms in the vagal sensory area (Xs) that could be involved in the generation of cardiorespiratory reflexes. The locations of the vagal sensory and motor (Xm) areas in the medulla were established by the orthograde and retrograde axonal transport of the neural tract tracer Fast Blue following its injection into the ganglion nodosum. Glutamate was then microinjected into identified sites within the Xs in an attempt to mimic chemoreceptor- and baroreceptor-induced reflexes commonly observed in fish. By necessity, the brain injections were performed on anaesthetised animals that were fixed by 'eye bars' in a recirculating water system. Blood pressure and heart rate were measured using an arterial cannula positioned in the afferent branchial artery of the 3rd gill arch, and ventilation was measured by impedance probes sutured onto the operculum. Unilateral injection of glutamate (40-100 nl, 10 mmol l(-1)) into the Xs caused marked cardiorespiratory changes. Injection (0.1-0.3 mm deep) in different rostrocaudal, medial-lateral positions induced a bradycardia, either increased or decreased blood pressure, ventilation frequency and amplitude and, sometimes, an initial apnea. Often these responses occurred simultaneously in various different combinations but, occasionally, they appeared singly, suggesting specific projections into the Xs for each cardiorespiratory variable and local determination of the modality of the response. Response patterns related to

  3. NEURON and Python.

    PubMed

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  4. NEURON and Python

    PubMed Central

    Hines, Michael L.; Davison, Andrew P.; Muller, Eilif

    2008-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications. PMID:19198661

  5. High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs.

    PubMed

    Roberts, Brandon L; Zhu, Mingyan; Zhao, Huan; Dillon, Crystal; Appleyard, Suzanne M

    2017-09-01

    Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT 3 Rs. Decreasing the glucose concentration also decreased both basal and 5-HT 3 R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT 3 R activity, and glucokinase. Copyright © 2017 the American Physiological Society.

  6. Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.

    PubMed

    Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

    2015-10-26

    Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.

  7. Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury

    PubMed Central

    Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

    2015-01-01

    Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion. PMID:26499847

  8. Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

    PubMed

    Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

    2017-01-01

    Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

  9. Reduced heart rate variability and vagal tone in anxiety: trait versus state, and the effects of autogenic training.

    PubMed

    Miu, Andrei C; Heilman, Renata M; Miclea, Mircea

    2009-01-28

    This study investigated heart rate variability (HRV) in healthy volunteers that were selected for extreme scores of trait anxiety (TA), during two opposite psychophysiological conditions of mental stress, and relaxation induced by autogenic training. R-R intervals, HF and LF powers, and LF/HF ratios were derived from short-term electrocardiographic recordings made during mental stress and relaxation by autogenic training, with respiratory rate and skin conductance being controlled for in all the analyses. The main finding was that high TA was associated with reduced R-R intervals and HF power across conditions. In comparison to mental stress, autogenic training increased HRV and facilitated the vagal control of the heart. There were no significant effects of TA or the psychophysiological conditions on LF power, or LF/HF ratio. These results support the view that TA, which is an important risk factor for anxiety disorders and predictor of cardiovascular morbidity and mortality, is associated with autonomic dysfunction that seems likely to play a pathogenetic role in the long term.

  10. Respiratory Sinus Arrhythmia as an Index of Vagal Activity during Stress in Infants: Respiratory Influences and Their Control

    PubMed Central

    Ritz, Thomas; Bosquet Enlow, Michelle; Schulz, Stefan M.; Kitts, Robert; Staudenmayer, John; Wright, Rosalind J.

    2012-01-01

    Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0–58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology. PMID:23300753

  11. Radiofrequency Catheter Ablation for Atrial Fibrillation Elicited "Jackhammer Esophagus": A New Complication Due to Vagal Nerve Stimulation?

    PubMed

    Tolone, Salvatore; Savarino, Edoardo; Docimo, Ludovico

    2015-10-01

    Radiofrequency catheter ablation (RFCA) is a potentially curative method for treatment of highly symptomatic and drug-refractory atrial fibrillation (AF). However, this technique can provoke esophageal and nerve lesion, due to thermal injury. To our knowledge, there have been no reported cases of a newly described motor disorder, the Jackhammer esophagus (JE) after RFCA, independently of GERD. We report a case of JE diagnosed by high-resolution manometry (HRM), in whom esophageal symptoms developed 2 weeks after RFCA, in absence of objective evidence of GERD. A 65-year-old male with highly symptomatic, drug-refractory paroxysmal AF was candidate to complete electrical pulmonary vein isolation with RFCA. Prior the procedure, the patient underwent HRM and impedance-pH to rule out GERD or hiatal hernia presence. All HRM parameters, according to Chicago classification, were within normal limits. No significant gastroesophageal reflux was documented at impedance pH monitoring. Patient underwent RFCA with electrical disconnection of pulmonary vein. After two weeks, patient started to complain of dysphagia for solids, with acute chest-pain. The patient repeated HRM and impedance-pH monitoring 8 weeks after RFCA. HRM showed in all liquid swallows the typical spastic hypercontractile contractions consistent with the diagnosis of JE, whereas impedance-pH monitoring resulted again negative for GERD. Esophageal dysmotility can represent a possible complication of RFCA for AF, probably due to a vagal nerve injury, and dysphagia appearance after this procedure must be timely investigated by HRM.

  12. Tachycardia, reduced vagal capacity, and age-dependent ventricular dysfunction arising from diminished expression of the presynaptic choline transporter

    PubMed Central

    English, Brett A.; Appalsamy, Martin; Diedrich, Andre; Ruggiero, Alicia M.; Lund, David; Wright, Jane; Keller, Nancy R.; Louderback, Katherine M.; Robertson, David

    2010-01-01

    Healthy cardiovascular function relies on a balanced and responsive integration of noradrenergic and cholinergic innervation of the heart. High-affinity choline uptake by cholinergic terminals is pivotal for efficient ACh production and release. To date, the cardiovascular impact of diminished choline transporter (CHT) expression has not been directly examined, largely due to the transporter's inaccessibility in vivo. Here, we describe findings from cardiovascular experiments using transgenic mice that bear a CHT genetic deficiency. Whereas CHT knockout (CHT−/−) mice exhibit early postnatal lethality, CHT heterozygous (CHT+/−) mice survive, grow, and reproduce normally and exhibit normal spontaneous behaviors. However, the CHT+/− mouse heart displays significantly reduced levels of high-affinity choline uptake accompanied by significantly reduced levels of ACh. Telemeterized recordings of cardiovascular function in these mice revealed tachycardia and hypertension at rest. After treadmill exercise, CHT+/− mice exhibited slower heart rate recovery, consistent with a diminished cholinergic reserve, a contention validated through direct vagal nerve stimulation. Echocardiographic and histological experiments revealed an age-dependent decrease in fractional shortening, increased left ventricular dimensions, and increased ventricular fibrosis, consistent with ventricular dysfunction. These cardiovascular phenotypes of CHT+/− mice encourage an evaluation of humans bearing reduced CHT expression for their resiliency in maintaining proper heart function as well as risk for cardiovascular disease. PMID:20601463

  13. Tachycardia, reduced vagal capacity, and age-dependent ventricular dysfunction arising from diminished expression of the presynaptic choline transporter.

    PubMed

    English, Brett A; Appalsamy, Martin; Diedrich, Andre; Ruggiero, Alicia M; Lund, David; Wright, Jane; Keller, Nancy R; Louderback, Katherine M; Robertson, David; Blakely, Randy D

    2010-09-01

    Healthy cardiovascular function relies on a balanced and responsive integration of noradrenergic and cholinergic innervation of the heart. High-affinity choline uptake by cholinergic terminals is pivotal for efficient ACh production and release. To date, the cardiovascular impact of diminished choline transporter (CHT) expression has not been directly examined, largely due to the transporter's inaccessibility in vivo. Here, we describe findings from cardiovascular experiments using transgenic mice that bear a CHT genetic deficiency. Whereas CHT knockout (CHT(-/-)) mice exhibit early postnatal lethality, CHT heterozygous (CHT(+/-)) mice survive, grow, and reproduce normally and exhibit normal spontaneous behaviors. However, the CHT(+/-) mouse heart displays significantly reduced levels of high-affinity choline uptake accompanied by significantly reduced levels of ACh. Telemeterized recordings of cardiovascular function in these mice revealed tachycardia and hypertension at rest. After treadmill exercise, CHT(+/-) mice exhibited slower heart rate recovery, consistent with a diminished cholinergic reserve, a contention validated through direct vagal nerve stimulation. Echocardiographic and histological experiments revealed an age-dependent decrease in fractional shortening, increased left ventricular dimensions, and increased ventricular fibrosis, consistent with ventricular dysfunction. These cardiovascular phenotypes of CHT(+/-) mice encourage an evaluation of humans bearing reduced CHT expression for their resiliency in maintaining proper heart function as well as risk for cardiovascular disease.

  14. How microglia kill neurons.

    PubMed

    Brown, Guy C; Vilalta, Anna

    2015-12-02

    Microglia are resident brain macrophages that become inflammatory activated in most brain pathologies. Microglia normally protect neurons, but may accidentally kill neurons when attempting to limit infections or damage, and this may be more common with degenerative disease as there was no significant selection pressure on the aged brain in the past. A number of mechanisms by which activated microglia kill neurons have been identified, including: (i) stimulation of the phagocyte NADPH oxidase (PHOX) to produce superoxide and derivative oxidants, (ii) expression of inducible nitric oxide synthase (iNOS) producing NO and derivative oxidants, (iii) release of glutamate and glutaminase, (iv) release of TNFα, (v) release of cathepsin B, (vi) phagocytosis of stressed neurons, and (vii) decreased release of nutritive BDNF and IGF-1. PHOX stimulation contributes to microglial activation, but is not directly neurotoxic unless NO is present. NO is normally neuroprotective, but can react with superoxide to produce neurotoxic peroxynitrite, or in the presence of hypoxia inhibit mitochondrial respiration. Glutamate can be released by glia or neurons, but is neurotoxic only if the neurons are depolarised, for example as a result of mitochondrial inhibition. TNFα is normally neuroprotective, but can become toxic if caspase-8 or NF-κB activation are inhibited. If the above mechanisms do not kill neurons, they may still stress the neurons sufficiently to make them susceptible to phagocytosis by activated microglia. We review here whether microglial killing of neurons is an artefact, makes evolutionary sense or contributes in common neuropathologies and by what mechanisms. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The mirror neuron system.

    PubMed

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  16. Mesmerising mirror neurons.

    PubMed

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Partitioning neuronal variability

    PubMed Central

    Goris, Robbe L.T.; Movshon, J. Anthony; Simoncelli, Eero P.

    2014-01-01

    Responses of sensory neurons differ across repeated measurements. This variability is usually treated as stochasticity arising within neurons or neural circuits. However, some portion of the variability arises from fluctuations in excitability due to factors that are not purely sensory, such as arousal, attention, and adaptation. To isolate these fluctuations, we developed a model in which spikes are generated by a Poisson process whose rate is the product of a drive that is sensory in origin, and a gain summarizing stimulus-independent modulatory influences on excitability. This model provides an accurate account of response distributions of visual neurons in macaque LGN, V1, V2, and MT, revealing that variability originates in large part from excitability fluctuations which are correlated over time and between neurons, and which increase in strength along the visual pathway. The model provides a parsimonious explanation for observed systematic dependencies of response variability and covariability on firing rate. PMID:24777419

  18. Neuromorphic Silicon Neuron Circuits

    PubMed Central

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  19. Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.

    PubMed

    Furuta, Sadayoshi; Watanabe, Lisa; Doi, Seira; Horiuchi, Hiroshi; Matsumoto, Kenjiro; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

    2012-02-01

    Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Copyright © 2011 Wiley Periodicals, Inc.

  20. Neurons of human nucleus accumbens.

    PubMed

    Sazdanović, Maja; Sazdanović, Predrag; Zivanović-Macuzić, Ivana; Jakovljević, Vladimir; Jeremić, Dejan; Peljto, Amir; Tosevski, Jovo

    2011-08-01

    Nucleus accumbens is a part of the ventral striatum also known as a drug active brain region, especially related with drug addiction. The aim of the study was to investigate the Golgi morphology of the nucleus accumbens neurons. The study was performed on the frontal and sagittal sections of 15 human brains by the Golgi Kopsch method. We classified neurons in the human nucleus accumbens according to their morphology and size into four types: type I--fusiform neurons; type II--fusiform neurons with lateral dendrite, arising from a part of the cell body; type III--pyramidal-like neuron; type IV--multipolar neuron. The medium spiny neurons, which are mostly noted regarding to the drug addictive conditions of the brain, correspond to the type IV--multipolar neurons. Two regions of human nucleus accumbens could be clearly recognized on Nissl and Golgi preparations each containing different predominant neuronal types. Central part of nucleus accumbens, core region, has a low density of impregnated neurons with predominant type III, pyramidal-like neurons, with spines on secondary branches and rare type IV, multipolar neurons. Contrary to the core, peripheral region, shell of nucleus, has a high density of impregnated neurons predominantly contained of type I and type IV--multipolar neurons, which all are rich in spines on secondary and tertiary dendritic branches. Our results indicate great morphological variability of human nucleus accumbens neurons. This requires further investigations and clarifying clinical significance of this important brain region.

  1. Decreased cardiac vagal control in drug-naive patients with panic disorder: a case-control study in Taiwan.

    PubMed

    Chang, Hsin-An; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Kuo, Terry B J; Lu, Ru-Band; Huang, San-Yuan

    2013-06-01

    Cardiac autonomic dysregulation has been proposed in panic disorder (PD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed. Forty-eight drug-naïve individuals with PD and 202 healthy volunteers were recruited for a case-control analysis. We used the Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory to assess anxiety severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire. Patients exhibited reduced mean RR interval (816.94 ± 135.92 versus 873.47 ± 143.36 ms, P = 0.014) and HRV levels (Var 6.37 ± 1.32 versus 7.38 ± 0.95, LF 4.90 ± 1.63 versus5.82 ± 1.11 and HF 4.57 ± 1.53 versus 5.62 ± 1.24 [ln(ms2)], all P < 0.001) as compared to controls, which mainly suggested a reduction in cardiac vagal control in PD. The anxiety severity was negatively correlated with HRV levels (r = -0.29 for Var, r = -0.22 for LF and r = -0.28 for HF, all P < 0.001). The harm avoidance score (which has been suggested to be associated with serotonergic activity) was associated with decreased HRV levels (r = -0.22 for Var, P < 0.01, r = -0.14 for LF, P < 0.05 and r = -0.17 for HF, P < 0.01). This study demonstrates that PD is associated with cardiac autonomic dysregulation, highlighting the importance of assessing HRV in PD patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

  2. Vagal Intramuscular Arrays: The Specialized Mechanoreceptor Arbors That Innervate the Smooth Muscle Layers of the Stomach Examined in the Rat

    PubMed Central

    Powley, Terry L.; Hudson, Cherie N.; McAdams, Jennifer L.; Baronowsky, Elizabeth A.; Phillips, Robert J.

    2016-01-01

    The fundamental roles that the stomach plays in ingestion and digestion notwithstanding, little morphological information is available on vagal intramuscular arrays (IMAs), the afferents that innervate gastric smooth muscle. To characterize IMAs better, rats were given injections of dextran biotin in the nodose ganglia, and, after tracer transport, stomach whole mounts were collected. Specimens were processed for avidin–biotin permanent labeling, and subsets of the whole mounts were immunohistochemically processed for c-Kit or stained with cuprolinic blue. IMAs (n = 184) were digitized for morphometry and mapping. Throughout the gastric muscle wall, IMAs possessed common phenotypic features. Each IMA was generated by a parent neurite arborizing extensively, forming an array of multiple (mean = 212) branches averaging 193 μm in length. These branches paralleled, and coursed in apposition with, bundles of muscle fibers and interstitial cells of Cajal. Individual arrays averaged 4.3 mm in length and innervated volumes of muscle sheet, presumptive receptive fields, averaging 0.1 mm3. Evaluated by region and by muscle sheet, IMAs displayed architectural adaptations to the different loci. A subset (32%) of circular muscle IMAs issued specialized polymorphic collaterals to myenteric ganglia, and a subset (41%) of antral longitudinal muscle IMAs formed specialized net endings associated with the serosal boundary. IMAs were concentrated in regional patterns that correlated with the unique biomechanical adaptations of the stomach, specifically proximal stomach reservoir functions and antral emptying operations. Overall, the structural adaptations and distributions of the IMAs were consonant with the hypothesized stretch receptor roles of the afferents. PMID:26355387

  3. Respiratory-phase domain analysis of heart rate variability can accurately estimate cardiac vagal activity during a mental arithmetic task.

    PubMed

    Kotani, Kiyoshi; Takamasu, Kiyoshi; Tachibana, Makoto

    2007-01-01

    The objectives of this paper were to present a method to extract the amplitude of RSA in the respiratory-phase domain, to compare that with subjective or objective indices of the MWL (mental workload), and to compare that with a conventional frequency analysis in terms of its accuracy during a mental arithmetic task. HRV (heart rate variability), ILV (instantaneous lung volume), and motion of the throat were measured under a mental arithmetic experiment and subjective and objective indices were also obtained. The amplitude of RSA was extracted in the respiratory-phase domain, and its correlation with the load level was compared with the results of the frequency domain analysis, which is the standard analysis of the HRV. The subjective and objective indices decreased as the load level increased, showing that the experimental protocol was appropriate. Then, the amplitude of RSA in the respiratory-phase domain also decreased with the increase in the load level. The results of the correlation analysis showed that the respiratory-phase domain analysis has higher negative correlations, -0.84 and -0.82, with the load level as determined by simple correlation and rank correlation, respectively, than does frequency analysis, for which the correlations were found to be -0.54 and -0.63, respectively. In addition, it was demonstrated that the proposed method could be applied to the short-term extraction of RSA amplitude. We proposed a simple and effective method to extract the amplitude of the respiratory sinus arrhythmia (RSA) in the respiratory-phase domain and the results show that this method can estimate cardiac vagal activity more accurately than frequency analysis.

  4. Neuronal avalanches and learning

    NASA Astrophysics Data System (ADS)

    de Arcangelis, Lucilla

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

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

    PubMed

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

    2017-06-01

    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. 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. 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. 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-dependent action. © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle

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

    PubMed Central

    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

  7. High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake.

    PubMed

    Byerly, Mardi S; Fox, Edward A

    2006-06-12

    Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.

  8. The effects of chronic consumption of heroin on basal and vagal electrical-stimulated gastric acid and pepsin secretion in rat.

    PubMed

    Rafsanjani, Fatemeh N; Maghouli, Fatemeh; Vahedian, Jalal; Esmaeili, Farzaneh

    2004-10-01

    Addiction to opium and heroin is not only an important social and individual problem in the world but it also affects the human physiology and multiple systems. The aim of this study is to determine the effects of chronic heroin consumption on basal and vagus electrical-stimulated total gastric acid and pepsin secretion in rats. The study was carried out in the Department of Physiology, Kerman University of Medical Sciences, Iran from August 2002 to June 2003. Both male and female rats weighing 200-250 g were used. Rats received daily doses of heroin intraperitoneally starting from 0.2 mg/kg to 0.1 mg/kg/day up to the maintenance level of 0.7 mg/kg and continued until day 12. After anesthesia, tracheotomy and laparotomy, gastric effluents were collected by washout technique with a 15 minutes interval. The total titrable acid was measured by manual titrator, and the total pepsin content was measured by Anson's method. Vagal electrical stimulation was used to stimulate the secretion of acid and pepsin. Heroin results in a significant decrease in total basal acid and pepsin secretions (4.10 +/- 0.18 mmol/15 minutes versus 2.40 +/- 0.16 mmol/15 minutes for acid, p<0.01, and 3.63 +/- 0.18 mg/15 minutes versus 3.11+/- 0.18 mg/15 minutes for pepsin, p<0.05). But, it does not produce any significant changes in acid and pepsin secretions in vagotomized condition. Heroin also causes a significant decrease in vagal-electrically stimulated acid and pepsin secretions (14.70 +/- 0.54 mmol/15 minutes versus 4.30 +/- 0.21 mmol/15 minutes for acid, p<0.01, and 3.92 +/-0.16 mg/15 minutes versus 3.37+/- 0.16 mg/15 minutes for pepsin, p<0.05). Heroin consumption decreases the total gastric basal and vagus stimulation of acid and pepsin secretion, but not in vagotomized condition. Heroin may decrease acid secretion by inhibiting vagal release of acetylcholine within the gastric wall. Other probable mechanisms include: presynaptic inhibition of acetylcholine release or depressing the

  9. Neuronal survival in the brain: neuron type-specific mechanisms.

    PubMed

    Pfisterer, Ulrich; Khodosevich, Konstantin

    2017-03-02

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

  10. Imaging voltage in neurons

    PubMed Central

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  11. Neuronal Mechanisms of Intelligence

    DTIC Science & Technology

    1987-11-01

    1984). Calcium-dependent protein kinases and neuronal function. Trends in PharmacologicaL Sciences, 5, 188-192. Schwartzkroin , P . A . (1981). To...arding electrical stimulus. Animals with nucleus •’• a ~CCumbens electrodes were wtraied in one-hour daily sesions to nose-poke for C p ! L. Stein & J.D...D O FILE. COR a AFOSR Grant #84-0325 Final Technical Report November 1987 AFOSR.T- 88-02. Cn’ NEURONAL MECHANISMS OF INTELLIGENCE DEPARTMENT OF

  12. Hypothalamic nutrient sensing activates a forebrain-hindbrain neuronal circuit to regulate glucose production in vivo.

    PubMed

    Lam, Carol K L; Chari, Madhu; Rutter, Guy A; Lam, Tony K T

    2011-01-01

    Hypothalamic nutrient sensing regulates glucose production, but the neuronal circuits involved remain largely unknown. Recent studies underscore the importance of N-methyl-d-aspartate (NMDA) receptors in the dorsal vagal complex in glucose regulation. These studies raise the possibility that hypothalamic nutrient sensing activates a forebrain-hindbrain NMDA-dependent circuit to regulate glucose production. We implanted bilateral catheters targeting the mediobasal hypothalamus (MBH) (forebrain) and dorsal vagal complex (DVC) (hindbrain) and performed intravenous catheterizations to the same rat for infusion and sampling purposes. This model enabled concurrent selective activation of MBH nutrient sensing by either MBH delivery of lactate or an adenovirus expressing the dominant negative form of AMPK (Ad-DN AMPK α2 [D¹⁵⁷A]) and inhibition of DVC NMDA receptors by either DVC delivery of NMDA receptor blocker MK-801 or an adenovirus expressing the shRNA of NR1 subunit of NMDA receptors (Ad-shRNA NR1). Tracer-dilution methodology and the pancreatic euglycemic clamp technique were performed to assess changes in glucose kinetics in the same conscious, unrestrained rat in vivo. MBH lactate or Ad-DN AMPK with DVC saline increased glucose infusion required to maintain euglycemia due to an inhibition of glucose production during the clamps. However, DVC MK-801 negated the ability of MBH lactate or Ad-DN AMPK to increase glucose infusion or lower glucose production. Molecular knockdown of DVC NR1 of NMDA receptor via Ad-shRNA NR1 injection also negated MBH Ad-DN AMPK to lower glucose production. Molecular and pharmacological inhibition of DVC NMDA receptors negated hypothalamic nutrient sensing mechanisms activated by lactate metabolism or AMPK inhibition to lower glucose production. Thus, DVC NMDA receptor is required for hypothalamic nutrient sensing to lower glucose production and that hypothalamic nutrient sensing activates a forebrain-hindbrain circuit to lower

  13. Degree Of Diminution In Vagal-Cardiac Activity Predicts Sudden Death In Familial Dysautonomia When Resting Tachycardia Is Absent

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Marthol, H.; Bucchner, S.; Tutaj, M.; Berlin, D.; Axelrod, F. B.; Hilz, M. J.

    2004-01-01

    Patients with familial dysautonomia (FD) have an increased risk of sudden death, but sensitive and specific predictors of sudden death in FD are lacking. Methods. We recorded 10-min resting high-fidelity 12-lead ECGs in 14 FD patients and in 14 age/gender-matched healthy subjects and studied 25+ different heart rate variability (HRV) indices for their ability to predict sudden death in the FD patients. Indices studied included those from 4 "nonlinear" HRV techniques (detrended fluctuation analysis, approximate entropy, correlation dimension, and PoincarC analyses). The predictive value of PR, QRS, QTc and JTc intervals, QT dispersion (QTd), beat-to-beat QT and PR interval variability indices (QTVI and PRVI) and 12- lead high frequency QRS ECG (150-250 Hz) were also studied. FD patients and controls (C) differed (Pless than 0.0l) with respect to 20+ of the HRV indices (FD less than C) and with respect to QTVI and PRVI (FDBC) and HF QRS- related root mean squared voltages (FDBC) and reduced amplitude zone counts (FD less than C). They differed less with respect to PR intervals (FD less than C) and JTc intervals (FD greater than C) (P less than 0.05 for both) and did not differ at all with respect to QRS and QTc intervals and to QTd. Within 12 months after study, 2 of the 14 patients succumbed to sudden cardiac arrest. The best predictor of sudden death was the degree of diminution in HRV vagal-cardiac (parasympathetic) parameters such as RMSSD, the SDl of Poincare plots, and HF spectral power. Excluding the two FD patients who had resting tachycardia (HR greater than 100, which confounds traditional HRV analyses), the following criteria were independently 100% sensitive and 100% specific for predicting sudden death in the remaining 12 FD patients during spontaneous breathing: RMSSD less than 13 ms and/or PoincarC SD1 less than 9 ms. In FD patients without supine tachycardia, the degree of diminution in parasympathetic HRV parameters (by high-fidelity ECG) predicts

  14. A Unique Case of Carotid Splaying by a Cervical Vagal Neurofibroma and the Role of Neuroradiology in Surgical Management

    PubMed Central

    Buehler, Mark; Mrak, Robert E; Mansour, Tarek R; Medhkour, Yacine; Medhkour, Azedine

    2017-01-01

    Carotid splaying, also known as the Lyre sign, is a widening of the carotid bifurcation due to the displacement of the internal carotid artery and the external carotid artery just distal to the point of divergence. This phenomenon is classically exhibited by highly vascularized carotid body tumors and, in rare cases, by cervical sympathetic chain schwannomas. Demonstration of the Lyre sign by a cervical vagal neurofibroma, however, is a unique occurrence that has not been previously documented in the literature. Neurofibromas are slow growing, poorly vascularized soft tissue masses and are a hallmark of the autosomal dominant genetic disorder, neurofibromatosis type 1 (NF-1). While targeted genetic therapies are evolving, management is currently dependent on a case-by-case resection of tumors with specific indications for chemo and radiation therapy. These resections rely on magnetic resonance imaging (MRI) to visualize tumor location and infiltration, but even in the setting of an established NF-1 diagnosis, additional imaging can be beneficial in ruling out more precarious tumors and optimizing surgical outcomes. In this case, a 25-year-old female with known NF-1 presented with an enlarging cervical mass that demonstrated splaying of the left internal and external carotid arteries on MRI. Due to the typical association of the Lyre sign with carotid body tumors, magnetic resonance angiography (MRA) was crucial in guiding surgical decision making. Carotid body tumors are highly vascularized, may compress carotid branches, and carry a high risk of intraoperative bleeding. They are best visualized with MRA, which assesses carotid splaying and patency, and demonstrates vascular blushing within the tumor.  This patient's MRA demonstrated the Lyre sign, patency of all carotid vessels, and a lack of vascularity within the mass, thus lowering suspicion for a carotid body tumor. Intraoperative use of imaging results facilitated a successful resection of a soft tissue

  15. The Reliability of Neurons

    PubMed Central

    Bullock, Theodore Holmes

    1970-01-01

    The prevalent probabilistic view is virtually untestable; it remains a plausible belief. The cases usually cited can not be taken as evidence for it. Several grounds for this conclusion are developed. Three issues are distinguished in an attempt to clarify a murky debate: (a) the utility of probabilistic methods in data reduction, (b) the value of models that assume indeterminacy, and (c) the validity of the inference that the nervous system is largely indeterministic at the neuronal level. No exception is taken to the first two; the second is a private heuristic question. The third is the issue to which the assertion in the first two sentences is addressed. Of the two kinds of uncertainty, statistical mechanical (= practical unpredictability) as in a gas, and Heisenbergian indeterminancy, the first certainly exists, the second is moot at the neuronal level. It would contribute to discussion to recognize that neurons perform with a degree of reliability. Although unreliability is difficult to establish, to say nothing of measure, evidence that some neurons have a high degree of reliability, in both connections and activity is increasing greatly. An example is given from sternarchine electric fish. PMID:5462670

  16. The neuron classification problem

    PubMed Central

    Bota, Mihail; Swanson, Larry W.

    2007-01-01

    A systematic account of neuron cell types is a basic prerequisite for determining the vertebrate nervous system global wiring diagram. With comprehensive lineage and phylogenetic information unavailable, a general ontology based on structure-function taxonomy is proposed and implemented in a knowledge management system, and a prototype analysis of select regions (including retina, cerebellum, and hypothalamus) presented. The supporting Brain Architecture Knowledge Management System (BAMS) Neuron ontology is online and its user interface allows queries about terms and their definitions, classification criteria based on the original literature and “Petilla Convention” guidelines, hierarchies, and relations—with annotations documenting each ontology entry. Combined with three BAMS modules for neural regions, connections between regions and neuron types, and molecules, the Neuron ontology provides a general framework for physical descriptions and computational modeling of neural systems. The knowledge management system interacts with other web resources, is accessible in both XML and RDF/OWL, is extendible to the whole body, and awaits large-scale data population requiring community participation for timely implementation. PMID:17582506

  17. Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

    PubMed

    Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

    2016-12-01

    Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Variable expression of GFP in different populations of peripheral cholinergic neurons of ChATBAC-eGFP transgenic mice.

    PubMed

    Brown, T Christopher; Bond, Cherie E; Hoover, Donald B

    2018-03-01

    Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons

    PubMed Central

    Yang, Chun; McKenna, James T.; Zant, Janneke C.; Winston, Stuart; Basheer, Radhika

    2014-01-01

    The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+ and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically

  20. Interplay between inflammation, immune system and neuronal pathways: Effect on gastrointestinal motility

    PubMed Central

    De Winter, Benedicte Y; De Man, Joris G

    2010-01-01

    Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients, mostly due to multiple organ failure. The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsis-induced multiple organ failure through intestinal barrier dysfunction, bacterial translocation and ileus. In this review we address the role of the gastrointestinal tract, the mediators, cell types and transduction pathways involved, based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data. The complex interplay within the gastrointestinal wall between mast cells, residential macrophages and glial cells on the one hand, and neurons and smooth muscle cells on the other hand, involves intracellular signaling pathways, Toll-like receptors and a plethora of neuroactive substances such as nitric oxide, prostaglandins, cytokines, chemokines, growth factors, tryptases and hormones. Multidirectional signaling between the different components in the gastrointestinal wall, the spinal cord and central nervous system impacts inflammation and its consequences. We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility, gastrointestinal sensitivity and even pain signaling on the other hand, for instance by impeding afferent neuronal signaling, by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system. PMID:21105185

  1. Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

    NASA Technical Reports Server (NTRS)

    Gonschorek, A. S.; Lu, L. L.; Halliwill, J. R.; Beightol, L. A.; Taylor, J. A.; Painter, J. A.; Warzel, H.; Eckberg, D. L.

    2001-01-01

    Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

  2. Life and Death of a Neuron

    MedlinePlus

    ... free mailed brochure Table of Contents Introduction The Architecture of the Neuron Birth Migration Differentiation Death Hope ... generated neurons in learning and memory. Neuron The Architecture of the Neuron The central nervous system (which ...

  3. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    PubMed

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  4. Neuronal synchrony: Peculiarity and generality

    PubMed Central

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I.

    2008-01-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their “dynamical repertoire” includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). PMID:19045493

  5. Criticality in Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Friedman, Nir; Ito, Shinya; Brinkman, Braden A. W.; Shimono, Masanori; Deville, R. E. Lee; Beggs, John M.; Dahmen, Karin A.; Butler, Tom C.

    2012-02-01

    In recent years, experiments detecting the electrical firing patterns in slices of in vitro brain tissue have been analyzed to suggest the presence of scale invariance and possibly criticality in the brain. Much of the work done however has been limited in two ways: 1) the data collected is from local field potentials that do not represent the firing of individual neurons; 2) the analysis has been primarily limited to histograms. In our work we examine data based on the firing of individual neurons (spike data), and greatly extend the analysis by considering shape collapse and exponents. Our results strongly suggest that the brain operates near a tuned critical point of a highly distinctive universality class.

  6. Single neuron modeling and data assimilation in BNST neurons

    NASA Astrophysics Data System (ADS)

    Farsian, Reza

    Neurons, although tiny in size, are vastly complicated systems, which are responsible for the most basic yet essential functions of any nervous system. Even the most simple models of single neurons are usually high dimensional, nonlinear, and contain many parameters and states which are unobservable in a typical neurophysiological experiment. One of the most fundamental problems in experimental neurophysiology is the estimation of these parameters and states, since knowing their values is essential in identification, model construction, and forward prediction of biological neurons. Common methods of parameter and state estimation do not perform well for neural models due to their high dimensionality and nonlinearity. In this dissertation, two alternative approaches for parameters and state estimation of biological neurons have been demonstrated: dynamical parameter estimation (DPE) and a Markov Chain Monte Carlo (MCMC) method. The first method uses elements of chaos control and synchronization theory for parameter and state estimation. MCMC is a statistical approach which uses a path integral formulation to evaluate a mean and an error bound for these unobserved parameters and states. These methods have been applied to biological system of neurons in Bed Nucleus of Stria Termialis neurons (BNST) of rats. State and parameters of neurons in both systems were estimated, and their value were used for recreating a realistic model and predicting the behavior of the neurons successfully. The knowledge of biological parameters can ultimately provide a better understanding of the internal dynamics of a neuron in order to build robust models of neuron networks.

  7. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    PubMed Central

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  8. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    PubMed

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  9. Metabolic reprogramming during neuronal differentiation.

    PubMed

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

  10. Metabolic reprogramming during neuronal differentiation

    PubMed Central

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-01-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate–glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K–Akt–mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  11. A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

    PubMed

    Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

    2015-08-13

    Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.

  12. Acute pancreatitis decreases the sensitivity of pancreas-projecting dorsal motor nucleus of the vagus neurones to group II metabotropic glutamate receptor agonists in rats

    PubMed Central

    Babic, Tanja; Travagli, R Alberto

    2014-01-01

    Recent studies have shown that pancreatic exocrine secretions (PES) are modulated by dorsal motor nucleus of the vagus (DMV) neurones, whose activity is finely tuned by GABAergic and glutamatergic synaptic inputs. Group II metabotropic glutamate receptors (mGluR) decrease synaptic transmission to pancreas-projecting DMV neurones and increase PES. In the present study, we used a combination of in vivo and in vitro approaches aimed at characterising the effects of caerulein-induced acute pancreatitis (AP) on the vagal neurocircuitry modulating pancreatic functions. In control rats, microinjection of bicuculline into the DMV increased PES, whereas microinjections of kynurenic acid had no effect. Conversely, in AP rats, microinjection of bicuculline had no effect, whereas kynurenic acid decreased PES. DMV microinjections of the group II mGluR agonist APDC and whole cell recordings of excitatory currents in identified pancreas-projecting DMV neurones showed a reduced functional response in AP rats compared to controls. Moreover, these changes persisted up to 3 weeks following the induction of AP. These data demonstrate that AP increases the excitatory input to pancreas-projecting DMV neurones by decreasing the response of excitatory synaptic terminals to group II mGluR agonist. PMID:24445314

  13. Neural mechanism of gastric motility regulation by electroacupuncture at RN12 and BL21: A paraventricular hypothalamic nucleus-dorsal vagal complex-vagus nerve-gastric channel pathway

    PubMed Central

    Wang, Hao; Liu, Wen-Jian; Shen, Guo-Ming; Zhang, Meng-Ting; Huang, Shun; He, Ying

    2015-01-01

    AIM: To study the neural mechanism by which electroacupuncture (EA) at RN12 (Zhongwan) and BL21 (Weishu) regulates gastric motility. METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custom-made rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex (DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin (MTL) and gastrin (GAS) in the paraventricular hypothalamic nucleus (PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor (MTL-R) and gastrin receptor (GAS-R) in both the PVN and the gastric antrum were assayed by western blotting. RESULTS: EA at RN12 + BL21 (gastric Shu and Mu points), BL21 (gastric Back-Shu point), RN12 (gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC (2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos (36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL (22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS (24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R (1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R (1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R (1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R (1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure (13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable

  14. Psychological Distress Following Marital Separation Interacts with a Polymorphism in the Serotonin Transporter Gene to Predict Cardiac Vagal Control in the Laboratory

    PubMed Central

    Hasselmo, Karen; Sbarra, David A.; O'Connor, Mary-Frances; Moreno, Francisco A.

    2015-01-01

    Marital separation is linked to negative mental and physical health; however, the strength of this link may vary across people. This study examined changes in respiratory sinus arrhythmia (RSA), used to assess cardiac vagal control, in recently separated adults (N = 79; M time since separation = 3.5 months). When reflecting over the separation, self-reported psychological distress following the separation interacted with a polymorphism in the serotonin transporter gene (5-HTTLPR) and a relevant single nucleotide polymorphism (SNP), rs25531, to predict RSA. Among people reporting emotional difficulties after the separation, those who were homozygous for the short allele had lower RSA levels while reflecting on their relationship than other genotypes. The findings, although limited by the relatively small sample size, are discussed in terms of how higher-sensitivity genotypes may interact with psychological responses to stress to alter physiology. PMID:25630596

  15. Psychological distress following marital separation interacts with a polymorphism in the serotonin transporter gene to predict cardiac vagal control in the laboratory.

    PubMed

    Hasselmo, Karen; Sbarra, David A; O'Connor, Mary-Frances; Moreno, Francisco A

    2015-06-01

    Marital separation is linked to negative mental and physical health; however, the strength of this link may vary across people. This study examined changes in respiratory sinus arrhythmia (RSA), used to assess cardiac vagal control, in recently separated adults (N = 79; M time since separation = 3.5 months). When reflecting on the separation, self-reported psychological distress following the separation interacted with a polymorphism in the serotonin transporter gene (5-HTTLPR) and a relevant single nucleotide polymorphism (SNP), rs25531, to predict RSA. Among people reporting emotional difficulties after the separation, those who were homozygous for the short allele had lower RSA levels while reflecting on their relationship than other genotypes. The findings, although limited by the relatively small sample size, are discussed in terms of how higher-sensitivity genotypes may interact with psychological responses to stress to alter physiology. © 2015 Society for Psychophysiological Research.

  16. Cross-correlation between vagal afferent impulses from pulmonary mechanoreceptors and high-frequency inflation (HFI) and deflation (HFD) in rabbits.

    PubMed

    Homma, I; Isobe, A; Iwase, M; Onimaru, H; Sibuya, M

    1987-04-10

    The effects of high-frequency airway inflation (HFI) and high-frequency airway deflation (HFD) generated by a triangular pressure pulse generator on pulmonary mechanoreceptors were examined. The cross-correlograms between vagal afferent impulses from the slowly adapting (SAR) and the rapidly adapting receptors (RAR) and the HFI or the HFD pulses were analysed. HFI stimulated SAR and RAR and HFD stimulated RAR, but inhibited SAR. The time lag of the mode in the correlogram between SAR and HFI was shorter than that of the mode in the correlogram between RAR and HFI. The span of the mode and the trough of SAR was shorter than the span of the mode of RAR. This may indicate that the time to peak of the generator potential of RAR is longer than that of SAR.

  17. Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

    PubMed

    Matsukawa, Kanji

    2012-01-01

    Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

  18. Analysis of the 2-deoxy-D-glucose-induced vagal stimulation of gastric secretion and gastrin release in dogs using methionine-enkephalin, morphine and naloxone.

    PubMed

    Anderson, W; Molina, E; Rentz, J; Hirschowitz, B I

    1982-09-01

    Gastric acid and pepsin secreted in 3 hr and antral gastrin released in response to vagal excitation induced by 2-deoxy-D-glucose (2DG), 625 mumol/kg i.v., were studied in six conscious trained gastric fistula dogs. During a 2-hr infusion, Met-enkephalin (96 nmol/kg/hr; delta receptor) reduced the 2DG response by 50%; when the enkephalin was stopped there was a rapid rebound to peak values. Met-enkephalin also blocked the release of gastrin in the first 15 min. By itself, Met-enkephalin did not stimulate secretion and slightly depressed gastrin. By contrast, morphine (96 nmol/kg/hr; mu receptor) augmented and sustained the 2DG gastric acid secretory response. This effect was blocked by naloxone. Morphine alone caused a small rise in serum gastrin after 90 min, followed by a delayed gastric acid secretion of about 30% of the peak 2DG response. Naloxone, a mu opiate antagonist (mu/delta, 27:1), also inhibited the 2DG gastric secretory response by about 50% and augmented the Met-enkephalin inhibition of secretion without blocking either the secretory rebound or the effect on gastrin release. None of the three opiates changed the direct cholinergic gastric secretory or gastrin-releasing effects of bethanechol. Thus, vagal stimulation of the stomach involves pathways which can be influenced by both mu and delta opiates, with apparently opposite effects, proximal to the level of acetylcholine action on the gastric mucosa. The central and peripheral control points in the activation of the stomach via the vagus which are sensitive to opiates have yet to be located and explained.

  19. The biophysics of neuronal growth

    NASA Astrophysics Data System (ADS)

    Franze, Kristian; Guck, Jochen

    2010-09-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  20. Steroid Treatment Reduces Allergic Airway Inflammation and Does Not Alter the Increased Numbers of Dendritic Cells and Calcitonin Gene-Related Peptide-Expressing Neurons in Airway Sensory Ganglia.

    PubMed

    Le, Duc Dung; Funck, Ulrike; Wronski, Sabine; Heck, Sebastian; Tschernig, Thomas; Bischoff, Markus; Sester, Martina; Herr, Christian; Bals, Robert; Welte, Tobias; Braun, Armin; Dinh, Quoc Thai

    2016-01-01

    Our previous data demonstrated that allergic airway inflammation induces migration of dendritic cells (DC) into airway sensory jugular and nodose ganglia (jugular-nodose ganglion complex; JNC). Here we investigated the effects of steroid treatment regarding the expression and migration of DC and calcitonin gene-related peptide (CGRP)-immunoreactive neurons of vagal sensory ganglia during allergic airway inflammation. A house dust mite (HDM) model for allergic airway inflammation was used. The mice received 0.3 mg fluticasone propionate per kilogram of body weight in the last 9 days. JNC slices were analyzed on MHC II, the neuronal marker PGP9.5, and the neuropeptide CGRP. Allergic airway inflammation increased the numbers of DC and CGRP-expressing neurons in the JNC significantly in comparison to the controls (DC/neurons: HDM 44.58 ± 1.6% vs. saline 33.29 ± 1.6%, p < 0.05; CGRP-positive neurons/total neurons: HDM 30.65 ± 1.9% vs. saline 19.49 ± 2.3%, p < 0.05). Steroid treatment did not have any effect on the numbers of DC and CGRP-expressing neurons in the JNC compared to HDM-treated mice. The present findings indicate an important role of DC and CGRP-containing neurons in the pathogenesis of allergic airway inflammation. However, steroid treatment did not have an effect on the population of DC and neurons displaying CGRP in the JNC, whereas steroid treatment was found to suppress allergic airway inflammation. © 2015 S. Karger AG, Basel.

  1. ReNeuron Group plc.

    PubMed

    Sinden, John D

    2006-01-01

    ReNeuron is a UK-based pioneer in stem cell research and development. The Company has leading edge, proprietary somatic stem cell technologies from which it is developing groundbreaking cell therapy products. ReNeuron's focus is on cell therapy treatments designed to reverse the effects of major diseases such as stroke, diabetes and diseases of the eye.

  2. Neuronal avalanches and coherence potentials

    NASA Astrophysics Data System (ADS)

    Plenz, D.

    2012-05-01

    The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

  3. The Neuronal Ceroid-Lipofuscinoses

    ERIC Educational Resources Information Center

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  4. Is realistic neuronal modeling realistic?

    PubMed Central

    Almog, Mara

    2016-01-01

    Scientific models are abstractions that aim to explain natural phenomena. A successful model shows how a complex phenomenon arises from relatively simple principles while preserving major physical or biological rules and predicting novel experiments. A model should not be a facsimile of reality; it is an aid for understanding it. Contrary to this basic premise, with the 21st century has come a surge in computational efforts to model biological processes in great detail. Here we discuss the oxymoronic, realistic modeling of single neurons. This rapidly advancing field is driven by the discovery that some neurons don't merely sum their inputs and fire if the sum exceeds some threshold. Thus researchers have asked what are the computational abilities of single neurons and attempted to give answers using realistic models. We briefly review the state of the art of compartmental modeling highlighting recent progress and intrinsic flaws. We then attempt to address two fundamental questions. Practically, can we realistically model single neurons? Philosophically, should we realistically model single neurons? We use layer 5 neocortical pyramidal neurons as a test case to examine these issues. We subject three publically available models of layer 5 pyramidal neurons to three simple computational challenges. Based on their performance and a partial survey of published models, we conclude that current compartmental models are ad hoc, unrealistic models functioning poorly once they are stretched beyond the specific problems for which they were designed. We then attempt to plot possible paths for generating realistic single neuron models. PMID:27535372

  5. Phenotypic Checkpoints Regulate Neuronal Development

    PubMed Central

    Ben-Ari, Yehezkel; Spitzer, Nicholas C.

    2010-01-01

    Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and may constitute presymptomatic signatures of neurological disorders when they go awry. PMID:20864191

  6. Anti-inflammatory effects and mechanisms of vagal nerve stimulation combined with electroacupuncture in a rodent model of TNBS-induced colitis.

    PubMed

    Jin, Haifeng; Guo, Jie; Liu, Jiemin; Lyu, Bin; Foreman, Robert D; Yin, Jieyun; Shi, Zhaohong; Chen, Jiande D Z

    2017-09-01

    The purpose of this study was to determine the effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-trinitrobenzenesulfonic acid). The rats were then treated with sham ES (electrical stimulation), VNS, or VNS + EA for 3 wk. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, plasma levels of TNFα, IL-1β, and IL-6, and myeloperoxidase (MPO) activity of colonic tissues. The autonomic function was assessed by the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. It was found that 1 ) the area under curve (AUC) of DAI was substantially decreased with VNS + EA and VNS, with VNS + EA being more effective than VNS ( P < 0.001); 2 ) the macroscopic score was 6.43 ± 0.61 in the sham ES group and reduced to 1.86 ± 0.26 with VNS ( P < 0.001) and 1.29 ± 0.18 with VNS + EA ( P < 0.001); 3 ) the histological score was 4.05 ± 0.58 in the sham ES group and reduced to 1.93 ± 0.37 with VNS ( P < 0.001) and 1.36 ± 0.20 with VNS + EA ( P < 0.001); 4 ) the plasma levels of TNFα, IL-1β, IL-6, and MPO were all significantly decreased with VNS and VNS + EA compared with the sham ES group; and 5 ) autonomically, both VNS + EA and VNS substantially increased vagal activity and decreased sympathetic activity compared with sham EA ( P < 0.001, P < 0.001, respectively). In conclusion, chronic VNS improves inflammation in TNBS-treated rats by inhibiting proinflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS. NEW & NOTEWORTHY This is the first study to address and compare the effects of vagal nerve stimulation (VNS), electrical acupuncture (EA) and VNS + EA on TNBS (2,4,6-trinitrobenzenesulfonic acid

  7. Neuronal pathway finding: from neurons to initial neural networks.

    PubMed

    Roscigno, Cecelia I

    2004-10-01

    Neuronal pathway finding is crucial for structured cellular organization and development of neural circuits within the nervous system. Neuronal pathway finding within the visual system has been extensively studied and therefore is used as a model to review existing knowledge regarding concepts of this developmental process. General principles of neuron pathway finding throughout the nervous system exist. Comprehension of these concepts guides neuroscience nurses in gaining an understanding of the developmental course of action, the implications of different anomalies, as well as the theoretical basis and nursing implications of some provocative new therapies being proposed to treat neurodegenerative diseases and neurologic injuries. These therapies have limitations in light of current ethical, developmental, and delivery modes and what is known about the development of neuronal pathways.

  8. Biosynthesis of Astrocytic Trehalose Regulates Neuronal Arborization in Hippocampal Neurons.

    PubMed

    Martano, Giuseppe; Gerosa, Laura; Prada, Ilaria; Garrone, Giulia; Krogh, Vittorio; Verderio, Claudia; Passafaro, Maria

    2017-09-20

    Trehalose is a nonreducing disaccharide that has recently attracted much attention because of its ability to inhibit protein aggregation, induce autophagy, and protect against dissections and strokes. In vertebrates, the biosynthesis of trehalose was long considered absent due to the lack of annotated genes involved in this process. In contrast, trehalase (TreH), which is an enzyme required for the cleavage of trehalose, is known to be conserved and expressed. Here, we show that trehalose is present as an endogenous metabolite in the rodent hippocampus. We found that primary astrocytes were able to synthesize trehalose and release it into the extracellular space. Notably, the TreH enzyme was observed only in the soma of neurons, which are the exclusive users of this substrate. A statistical analysis of the metabolome during different stages of maturation indicated that this metabolite is implicated in neuronal maturation. A morphological analysis of primary neurons confirmed that trehalose is required for neuronal arborization.

  9. A novel surgical procedure of vagal nerve, lower esophageal sphincter, and pyloric sphincter-preserving nearly total gastrectomy reconstructed by single jejunal interposition, and postoperative quality of life.

    PubMed

    Tomita, Ryouichi

    2005-01-01

    For early gastric cancer total gastrectomy (TG) has so far been essentially unavoidable. We performed the nearly TG reconstructed by single jejunal interposition preservation of the vagal nerve, lower esophageal sphincter (LES) and pyloric sphincter (D1 or D2 lymph node dissection, curability A) as a function-preserving surgical technique (i.e. NTG) to improve postoperative quality of life (QOL). In this report, the application criteria and points of the technique are outlined. QOL in patients after NTG was also compared with those after TG. Sixteen subjects who underwent NTG (12 men and 4 women subjects at age 30 to 70 years, mean 55.6 years) were interviewed to inquire about abdominal symptoms and compared with 20 patients after conventional TG (excision with D2 lymph node, radical curability A) reconstructed by single jejunal interposition without preserving the vagal nerve, LES, and pyloric sphincter (i.e. TGI; 14 men and 6 women at age 26 to 70 years, mean 54.8 years). The former was named group A and the latter group B. Included were cases with early cancer localizing at the upper third and middle stomach, 2cm or further in distance from oral-side margin of the cancer to esophagogastric mucosal junction; and 3.5cm or further in distance from anal-side margin of the cancer to the pyloric sphincter. In excision with the lymph node, hepatic and celiac branches were preserved. To preserve LES, the abdominal esophagus was completely preserved. The pyloric antrum was also preserved at 1.5cm from the pyloric sphincter. The substitute stomach was created as a 30-cm-long single jejunal segment having orthodromic peristaltic movement. The operative procedure in group A significantly improved postoperative gastrointestinal symptoms such as appetite loss (p=0.0004), weight loss (p=0.0369), reflux esophagitis (RE) (p=0.0163), early dumping syndrome (p=0.0163), endoscopic RE (p=0.0311), and postgastrectomy cholecystolithiasis (p=0.0163) compared with group B. Oral intake

  10. Glial tumors with neuronal differentiation.

    PubMed

    Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

    2015-01-01

    Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Mechanosensing in hypothalamic osmosensory neurons.

    PubMed

    Prager-Khoutorsky, Masha

    2017-11-01

    Osmosensory neurons are specialized cells activated by increases in blood osmolality to trigger thirst, secretion of the antidiuretic hormone vasopressin, and elevated sympathetic tone during dehydration. In addition to multiple extrinsic factors modulating their activity, osmosensory neurons are intrinsically osmosensitive, as they are activated by increased osmolality in the absence of neighboring cells or synaptic contacts. This intrinsic osmosensitivity is a mechanical process associated with osmolality-induced changes in cell volume. This review summarises recent findings revealing molecular mechanisms underlying the mechanical activation of osmosensory neurons and highlighting important roles of microtubules, actin, and mechanosensitive ion channels in this process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Simulating synchronization in neuronal networks

    NASA Astrophysics Data System (ADS)

    Fink, Christian G.

    2016-06-01

    We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.

  13. Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death

    PubMed Central

    Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

    2016-01-01

    Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5+ endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. DOI: http://dx.doi.org/10.7554/eLife.11627.001 PMID:26857994

  14. A fish on the hunt, observed neuron by neuron

    SciT

    None

    2010-01-01

    This three-dimensional microscopy image reveals an output neuron of the optic tectum lighting up in response to visual information from the retina. The scientists used this state-of-the-art imaging technology to learn how neurons in the optic tectum take visual information and convert it into an output that drives action. More information: http://newscenter.lbl.gov/feature-stories/2010/10/29/zebrafish-vision/

  15. Neurons on the couch.

    PubMed

    Marić, Nadja P; Jašović-Gašić, Miroslava

    2010-12-01

    A hundred years after psychoanalysis was introduced, neuroscience has taken a giant step forward. It seems nowadays that effects of psychotherapy could be monitored and measured by state-of-the art brain imaging techniques. Today, the psychotherapy is considered as a strategic and purposeful environmental influence intended to enhance learning. Since gene expression is regulated by environmental influences throughout life and these processes create brain architecture and influence the strength of synaptic connections, psychotherapy (as a kind of learning) should be explored in the context of aforementioned paradigm. In other words, when placing a client on the couch, therapist actually placed client's neuronal network; while listening and talking, expressing and analyzing, experiencing transference and counter transference, therapist tends to stabilize synaptic connections and influence dendritic growth by regulating gene-transcriptional activity. Therefore, we strongly believe that, in the near future, an increasing knowledge on cellular and molecular interactions and mechanisms of action of different psycho- and pharmaco-therapeutic procedures will enable us to tailor a sophisticated therapeutic approach toward a person, by combining major therapeutic strategies in psychiatry on the basis of rational goals and evidence-based therapeutic expectations.

  16. Tinbergen on mirror neurons.

    PubMed

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.

  17. Tinbergen on mirror neurons

    PubMed Central

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376

  18. Neuronal boost to evolutionary dynamics

    PubMed Central

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  19. Neuronal boost to evolutionary dynamics.

    PubMed

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-06

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild.

  20. Bayesian Networks Predict Neuronal Transdifferentiation.

    PubMed

    Ainsworth, Richard I; Ai, Rizi; Ding, Bo; Li, Nan; Zhang, Kai; Wang, Wei

    2018-05-30

    We employ the language of Bayesian networks to systematically construct gene-regulation topologies from deep-sequencing single-nucleus RNA-Seq data for human neurons. From the perspective of the cell-state potential landscape, we identify attractors that correspond closely to different neuron subtypes. Attractors are also recovered for cell states from an independent data set confirming our models accurate description of global genetic regulations across differing cell types of the neocortex (not included in the training data). Our model recovers experimentally confirmed genetic regulations and community analysis reveals genetic associations in common pathways. Via a comprehensive scan of all theoretical three-gene perturbations of gene knockout and overexpression, we discover novel neuronal trans-differrentiation recipes (including perturbations of SATB2, GAD1, POU6F2 and ADARB2) for excitatory projection neuron and inhibitory interneuron subtypes. Copyright © 2018, G3: Genes, Genomes, Genetics.

  1. Neuronal control of energy homeostasis

    PubMed Central

    Gao, Qian; Horvath, Tamas L.

    2013-01-01

    Neuronal control of body energy homeostasis is the key mechanism by which animals and humans regulate their long-term energy balance. Various hypothalamic neuronal circuits (which include the hypothalamic melanocortin, midbrain dopamine reward and caudal brainstem autonomic feeding systems) control energy intake and expenditure to maintain body weight within a narrow range for long periods of a life span. Numerous peripheral metabolic hormones and nutrients target these structures providing feedback signals that modify the default “settings” of neuronal activity to accomplish this balance. A number of molecular genetic tools for manipulating individual components of brain energy homeostatic machineries, in combination with anatomical, electrophysiological, pharmacological and behavioral techniques, have been developed, which provide a means for elucidating the complex molecular and cellular mechanisms of feeding behavior and metabolism. This review will highlight some of these advancements and focus on the neuronal circuitries of energy homeostasis. PMID:18061579

  2. Do enteric neurons make hypocretin?

    PubMed

    Baumann, Christian R; Clark, Erika L; Pedersen, Nigel P; Hecht, Jonathan L; Scammell, Thomas E

    2008-04-10

    Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin.

  3. Imitation, mirror neurons and autism.

    PubMed

    Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I

    2001-06-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.

  4. Network synchronization in hippocampal neurons.

    PubMed

    Penn, Yaron; Segal, Menahem; Moses, Elisha

    2016-03-22

    Oscillatory activity is widespread in dynamic neuronal networks. The main paradigm for the origin of periodicity consists of specialized pacemaking elements that synchronize and drive the rest of the network; however, other models exist. Here, we studied the spontaneous emergence of synchronized periodic bursting in a network of cultured dissociated neurons from rat hippocampus and cortex. Surprisingly, about 60% of all active neurons were self-sustained oscillators when disconnected, each with its own natural frequency. The individual neuron's tendency to oscillate and the corresponding oscillation frequency are controlled by its excitability. The single neuron intrinsic oscillations were blocked by riluzole, and are thus dependent on persistent sodium leak currents. Upon a gradual retrieval of connectivity, the synchrony evolves: Loose synchrony appears already at weak connectivity, with the oscillators converging to one common oscillation frequency, yet shifted in phase across the population. Further strengthening of the connectivity causes a reduction in the mean phase shifts until zero-lag is achieved, manifested by synchronous periodic network bursts. Interestingly, the frequency of network bursting matches the average of the intrinsic frequencies. Overall, the network behaves like other universal systems, where order emerges spontaneously by entrainment of independent rhythmic units. Although simplified with respect to circuitry in the brain, our results attribute a basic functional role for intrinsic single neuron excitability mechanisms in driving the network's activity and dynamics, contributing to our understanding of developing neural circuits.

  5. New Features for Neuron Classification.

    PubMed

    Hernández-Pérez, Leonardo A; Delgado-Castillo, Duniel; Martín-Pérez, Rainer; Orozco-Morales, Rubén; Lorenzo-Ginori, Juan V

    2018-04-28

    This paper addresses the problem of obtaining new neuron features capable of improving results of neuron classification. Most studies on neuron classification using morphological features have been based on Euclidean geometry. Here three one-dimensional (1D) time series are derived from the three-dimensional (3D) structure of neuron instead, and afterwards a spatial time series is finally constructed from which the features are calculated. Digitally reconstructed neurons were separated into control and pathological sets, which are related to three categories of alterations caused by epilepsy, Alzheimer's disease (long and local projections), and ischemia. These neuron sets were then subjected to supervised classification and the results were compared considering three sets of features: morphological, features obtained from the time series and a combination of both. The best results were obtained using features from the time series, which outperformed the classification using only morphological features, showing higher correct classification rates with differences of 5.15, 3.75, 5.33% for epilepsy and Alzheimer's disease (long and local projections) respectively. The morphological features were better for the ischemia set with a difference of 3.05%. Features like variance, Spearman auto-correlation, partial auto-correlation, mutual information, local minima and maxima, all related to the time series, exhibited the best performance. Also we compared different evaluators, among which ReliefF was the best ranked.

  6. Cardiac vagal control and theoretical models of co-occurring depression and anxiety: A cross-sectional psychophysiological study of community elderly

    PubMed Central

    2012-01-01

    Background 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) and pre-defined, theoretical factors from the Hospital Anxiety and Depression Scale (HADS). Methods Three hundred fifty-four randomly selected Chinese male subjects aged ≥65 years and living in the community were enrolled. CVC was measured using a frequency-domain index of heart rate variability. Results Confirmatory factor analysis showed that the flat tripartite model of HADS provided a modest advantage in model fit when compared with other theoretical factor solutions. In the flat tripartite model, there was a significant negative association between anhedonic depression and CVC. In contrast, autonomic anxiety showed a significant positive correlation with CVC. In the hierarchical tripartite model, negative affectivity was not directly associated with CVC; instead, it had positive and negative indirect effects on CVC via autonomic anxiety and anhedonic depression, respectively. As scores for negative affectivity increased, these specific indirect effects diminished. Conclusions Among competing models of co-occurring depression and anxiety, constructs from tripartite models demonstrate fair conformity with the data but unique and distinct correlations with CVC. Negative affectivity may determine the relationship of anhedonic depression and autonomic anxiety with CVC. Separating affective symptoms under the constructs of the tripartite models helps disentangle complex associations between co-occurring depression and anxiety with CVC. PMID:22846457

  7. Sympatho-vagal balance, as quantified by ANSindex, predicts post spinal hypotension and vasopressor requirement in parturients undergoing lower segmental cesarean section: a single blinded prospective observational study.

    PubMed

    Prashanth, Anitha; Chakravarthy, Murali; George, Antony; Mayur, Rohini; Hosur, Rajathadri; Pargaonkar, Sumant

    2017-08-01

    Hypotension subsequent to spinal anesthesia occurs in a significant number of parturients undergoing lower segment caesarian section. Currently available methods to predict the incidence of hypotension, its severity and the outcome are sub-optimal. Many workers have used basal heart rate as one of the predictors. But using this method it is not possible to objectively analyze and predict the extent and severity of hypotension. We used an equipment measuring the level of sympatho-vagal balance, ANSiscope™, which derives these values from computed value of RR interval variability. We made a single measure of the value which was blinded to the patient and the anesthesiologist. We studied one hundred eight patients who underwent lower segment caesarian section under spinal anesthesia and found the variability of preoperative ANSindex (% activity displayed by the equipment) from 9 to 65 %. Higher ANSindex value was significantly associated with post spinal hypotension (p 0.017). A value of 24 % indicated the critical level above which hypotension appeared commonly. The ANSindex value might help anesthesiologist to anticipate and prepare for hypotension that is likely to ensue.

  8. Impact of escitalopram on vagally mediated cardiovascular function in healthy participants: implications for understanding differential age-related, treatment emergent effects.

    PubMed

    Kemp, Andrew H; Outhred, Tim; Saunders, Sasha; Brunoni, Andre R; Nathan, Pradeep J; Malhi, Gin S

    2014-06-01

    Black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide. While underlying mechanisms for age-related treatment effects remain unclear, vagally mediated cardiovascular function may play a key role. Decreased heart rate (HR) and an increase in its variability (HRV) improve one's capacity to adapt to environmental stress and attenuate risk for suicide. Using a double blind, randomized, placebo-controlled, crossover, experimental study, we examine whether a single dose of escitalopram (20 mg) attenuates cardiovascular responses to stress under experimental conditions and determine whether age moderates these effects. Forty-four healthy females received a single dose of escitalopram (20 mg) and placebo treatment separated by a 1-week interval (>5 half-lives). HR and high frequency HRV (HF HRV normalized units; 0.15-0.40 Hz) were measured during resting state and stress. While escitalopram attenuated the increase in HR and increased HF HRV, these moderate to large effects were only significant in participants over 25 years of age. No beneficial cardiovascular effects of escitalopram were observed in those under the age of 25. Maturational differences in the development of the prefrontal cortex--a critical region in the central network of autonomic control--may underpin these differential findings. This study provides a theoretical framework on which future research on treatment-emergent suicidality in clinical populations could be based.

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

    NASA Technical Reports Server (NTRS)

    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.

  10. Communication among neurons.

    PubMed

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  11. Testicular regulation of neuronal glucose and monocarboxylate transporter gene expression profiles in CNS metabolic sensing sites during acute and recurrent insulin-induced hypoglycemia.

    PubMed

    Vavaiya, Kamlesh V; Paranjape, Sachin A; Briski, Karen P

    2007-01-01

    Recurrent insulin-induced hypoglycemia (RIIH) impairs glucose counter-regulatory function in male humans and rodents and, in the latter, diminishes neuronal activation in CNS structures that monitor metabolic homeostasis, including the lateral hypothalamic area (LHA) and dorsal vagal complex (DVC). We investigated whether habituated neuronal reactivity in CNS sensing sites to hypoglycemia is correlated with modified monocarboxylate and/or glucose uptake by using quantitative real-time RT-PCR to analyze neuronal monocarboxylate transporter (MCT2) and glucose transporter variant (GLUT and GLUT4) gene expression profiles in the microdissected LHA, ventromedial nucleus hypothalamus (VMH), and DVC after one or multiple insulin injections. Because orchidectomy (ORDX) maintains uniform glycemic responses to RIIH in male rats, we also examined whether regional gene response patterns are testes dependent. In the intact male rat DVC, MCT2, GLUT3, and GLUT4 gene expression was not altered by acute hypoglycemia but was enhanced by RIIH. MCT2 and GLUT3 mRNA levels in the ORDX rat DVC did not differ among groups, but GLUT4 transcripts were progressively increased by acute and recurrent hypoglycemia. Precedent hypoglycemia decreased or increased basal MCT2 and GLUT4 gene expression, respectively, in the intact rat LHA; LHA GLUT3 transcription was augmented by RIIH in intact rats only. Acute hypoglycemia suppressed MCT2, GLUT3, and GLUT4 gene expression in the intact rat VMH, a response that was abolished by RIIH. In ORDX rats, VMH gene transcript levels were unchanged in response to one dose of insulin but were selectively diminished during RIIH. These data demonstrate site-specific, testes-dependent effects of acute and recurrent hypoglycemia on neuronal metabolic substrate transporter gene expression in characterized rat brain metabolic sensing loci and emphasize the need to assess the impact of potential alterations in glucose and lactate uptake during RIIH on general and

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

    PubMed

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

    1996-03-01

    1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P < 0.005). Mechanical sensitivities of afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) from non-immunized control guinea-pig airways were unaffected by antigen (n = 13). 4. Antigen did not overtly cause action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in

  13. Acetylcholine-evoked currents in cultured neurones dissociated from rat parasympathetic cardiac ganglia.

    PubMed Central

    Fieber, L A; Adams, D J

    1991-01-01

    described mediate the responses of postganglionic parasympathetic neurones of the mammalian heart to vagal stimulation. PMID:1708819

  14. Fatty acids increase neuronal hypertrophy of Pten knockdown neurons

    PubMed Central

    Fricano, Catherine J.; DeSpenza, Tyrone; Frazel, Paul W.; Li, Meijie; O'Malley, A. James; Westbrook, Gary L.; Luikart, Bryan W.

    2014-01-01

    Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy could influence the severity of the Pten knockdown-induced hypertrophy. Implantation of mini-osmotic pumps delivering fatty acids results in increased neuronal hypertrophy and p-S6/p-mTOR staining. These hypertrophic effects were reversed in response to rapamycin treatment. However, we did not observe a similar increase in hypertrophy in response to dietary manipulations of fatty acids. Thus, we conclude that by driving growth signaling with fatty acids and knocking down a critical regulator of growth, Pten, we are able to observe an additive morphological phenotype of increased soma size mediated by the mTOR pathway. PMID:24795563

  15. Neuronize: a tool for building realistic neuronal cell morphologies

    PubMed Central

    Brito, Juan P.; Mata, Susana; Bayona, Sofia; Pastor, Luis; DeFelipe, Javier; Benavides-Piccione, Ruth

    2013-01-01

    This study presents a tool, Neuronize, for building realistic three-dimensional models of neuronal cells from the morphological information extracted through computer-aided tracing applications. Neuronize consists of a set of methods designed to build 3D neural meshes that approximate the cell membrane at different resolution levels, allowing a balance to be reached between the complexity and the quality of the final model. The main contribution of the present study is the proposal of a novel approach to build a realistic and accurate 3D shape of the soma from the incomplete information stored in the digitally traced neuron, which usually consists of a 2D cell body contour. This technique is based on the deformation of an initial shape driven by the position and thickness of the first order dendrites. The addition of a set of spines along the dendrites completes the model, building a final 3D neuronal cell suitable for its visualization in a wide range of 3D environments. PMID:23761740

  16. Neuronize: a tool for building realistic neuronal cell morphologies.

    PubMed

    Brito, Juan P; Mata, Susana; Bayona, Sofia; Pastor, Luis; Defelipe, Javier; Benavides-Piccione, Ruth

    2013-01-01

    This study presents a tool, Neuronize, for building realistic three-dimensional models of neuronal cells from the morphological information extracted through computer-aided tracing applications. Neuronize consists of a set of methods designed to build 3D neural meshes that approximate the cell membrane at different resolution levels, allowing a balance to be reached between the complexity and the quality of the final model. The main contribution of the present study is the proposal of a novel approach to build a realistic and accurate 3D shape of the soma from the incomplete information stored in the digitally traced neuron, which usually consists of a 2D cell body contour. This technique is based on the deformation of an initial shape driven by the position and thickness of the first order dendrites. The addition of a set of spines along the dendrites completes the model, building a final 3D neuronal cell suitable for its visualization in a wide range of 3D environments.

  17. The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

    PubMed

    Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

    2017-09-01

    The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few

  18. Neuronal factors determining high intelligence.

    PubMed

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

  19. The mirror-neuron system.

    PubMed

    Rizzolatti, Giacomo; Craighero, Laila

    2004-01-01

    A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.

  20. Brain Neurons as Quantum Computers:

    NASA Astrophysics Data System (ADS)

    Bershadskii, A.; Dremencov, E.; Bershadskii, J.; Yadid, G.

    The question: whether quantum coherent states can sustain decoherence, heating and dissipation over time scales comparable to the dynamical timescales of brain neurons, has been actively discussed in the last years. A positive answer on this question is crucial, in particular, for consideration of brain neurons as quantum computers. This discussion was mainly based on theoretical arguments. In the present paper nonlinear statistical properties of the Ventral Tegmental Area (VTA) of genetically depressive limbic brain are studied in vivo on the Flinders Sensitive Line of rats (FSL). VTA plays a key role in the generation of pleasure and in the development of psychological drug addiction. We found that the FSL VTA (dopaminergic) neuron signals exhibit multifractal properties for interspike frequencies on the scales where healthy VTA dopaminergic neurons exhibit bursting activity. For high moments the observed multifractal (generalized dimensions) spectrum coincides with the generalized dimensions spectrum calculated for a spectral measure of a quantum system (so-called kicked Harper model, actively used as a model of quantum chaos). This observation can be considered as a first experimental (in vivo) indication in the favor of the quantum (at least partially) nature of brain neurons activity.

  1. Dynamics of moment neuronal networks.

    PubMed

    Feng, Jianfeng; Deng, Yingchun; Rossoni, Enrico

    2006-04-01

    A theoretical framework is developed for moment neuronal networks (MNNs). Within this framework, the behavior of the system of spiking neurons is specified in terms of the first- and second-order statistics of their interspike intervals, i.e., the mean, the variance, and the cross correlations of spike activity. Since neurons emit and receive spike trains which can be described by renewal--but generally non-Poisson--processes, we first derive a suitable diffusion-type approximation of such processes. Two approximation schemes are introduced: the usual approximation scheme (UAS) and the Ornstein-Uhlenbeck scheme. It is found that both schemes approximate well the input-output characteristics of spiking models such as the IF and the Hodgkin-Huxley models. The MNN framework is then developed according to the UAS scheme, and its predictions are tested on a few examples.

  2. Neuronal clues to vascular guidance.

    PubMed

    Suchting, Steven; Bicknell, Roy; Eichmann, Anne

    2006-03-10

    The development of the vertebrate vascular system into a highly ordered and stereotyped network requires precise control over the branching and growth of new vessels. Recent research has highlighted the important role of genetic programs in regulating vascular patterning and in particular has established a crucial role for families of molecules previously described in controlling neuronal guidance. Like neurons, new vessels are guided along the correct path by integrating attractive and repulsive cues from the external environment. This is achieved by specialised endothelial cells at the leading tip of vessel sprouts which express receptor proteins that couple extracellular guidance signals with the cytoskeletal changes necessary to alter cell direction. Here, we review the genetic and in vitro evidence implicating four families of ligand-receptor signalling systems common to both neuronal and vessel guidance: the Ephrins and Eph receptors; Semaphorins, Neuropilins and Plexin receptors; Netrin and Unc5 receptors; and Slits and Robo receptors.

  3. Calcium signals in olfactory neurons.

    PubMed

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  4. Hyperthyroidism is characterized by both increased sympathetic and decreased vagal modulation of heart rate: evidence from spectral analysis of heart rate variability.

    PubMed

    Chen, Jin-Long; Chiu, Hung-Wen; Tseng, Yin-Jiun; Chu, Woei-Chyn

    2006-06-01

    The clinical manifestations of hyperthyroidism resemble those of the hyperadrenergic state. This study was designed to evaluate the impact of hyperthyroidism on the autonomic nervous system (ANS) and to investigate the relationship between serum thyroid hormone concentrations and parameters of spectral heart rate variability (HRV) analysis in hyperthyroidism. Thirty-two hyperthyroid Graves' disease patients (mean age 31 years) and 32 sex-, age-, and body mass index (BMI)-matched normal control subjects were recruited to receive one-channel electrocardiogram (ECG) recording. The cardiac autonomic nervous function was evaluated by the spectral analysis of HRV, which indicates the autonomic modulation of the sinus node. The correlation coefficients between serum thyroid hormone concentrations and parameters of the spectral HRV analysis were also computed. The hyperthyroid patients revealed significant differences (P < 0.001) compared with the controls in the following HRV parameters: a decrease in total power (TP), very low frequency power (VLF), low frequency power (LF), high frequency power (HF), and HF in normalized units (HF%); and an increase in LF in normalized units (LF%) and in the ratio of LF to HF (LF/HF). After correction of hyperthyroidism in 28 patients, all of the above parameters were restored to levels comparable to those of the controls. In addition, serum thyroid hormone concentrations showed significant correlations with spectral HRV parameters. Hyperthyroidism is in a sympathovagal imbalanced state, characterized by both increased sympathetic and decreased vagal modulation of the heart rate. These autonomic dysfunctions can be detected simultaneously by spectral analysis of HRV, and the spectral HRV parameters could reflect the disease severity in hyperthyroid patients.

  5. Resting cardiac vagal tone predicts intraindividual reaction time variability during an attention task in a sample of young and healthy adults.

    PubMed

    Williams, DeWayne P; Thayer, Julian F; Koenig, Julian

    2016-12-01

    Intraindividual reaction time variability (IIV), defined as the variability in trial-to-trial response times, is thought to serve as an index of central nervous system function. As such, greater IIV reflects both poorer executive brain function and cognitive control, in addition to lapses in attention. Resting-state vagally mediated heart rate variability (vmHRV), a psychophysiological index of self-regulatory abilities, has been linked with executive brain function and cognitive control such that those with greater resting-state vmHRV often perform better on cognitive tasks. However, research has yet to investigate the direct relationship between resting vmHRV and task IIV. The present study sought to examine this relationship in a sample of 104 young and healthy participants who first completed a 5-min resting-baseline period during which resting-state vmHRV was assessed. Participants then completed an attentional (target detection) task, where reaction time, accuracy, and trial-to-trial IIV were obtained. Results showed resting vmHRV to be significantly related to IIV, such that lower resting vmHRV predicted higher IIV on the task, even when controlling for several covariates (including mean reaction time and accuracy). Overall, our results provide further evidence for the link between resting vmHRV and cognitive control, and extend these notions to the domain of lapses in attention, as indexed by IIV. Implications and recommendations for future research on resting vmHRV and cognition are discussed. © 2016 Society for Psychophysiological Research.

  6. Monitoring of the posterior cricoarytenoid muscle represents another option for neural monitoring during thyroid surgery: Normative vagal and recurrent laryngeal nerve posterior cricoarytenoid muscle electromyographic data.

    PubMed

    Liddy, Whitney; Barber, Samuel R; Lin, Brian M; Kamani, Dipti; Kyriazidis, Natalia; Lawson, Bradley; Randolph, Gregory W

    2018-01-01

    Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. Retrospective review. Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. 4. Laryngoscope, 128:283-289, 2018. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Potential Role of Regulator of G-Protein Signaling 5 in the Protection of Vagal-Related Bradycardia and Atrial Tachyarrhythmia.

    PubMed

    Qin, Mu; Liu, Xu; Liu, Tao; Wang, Teng; Huang, Congxin

    2016-03-09

    The regulator of G-protein signaling 5 (Rgs5), which functions as the regulator of G-protein-coupled receptor (GPCR) including muscarinic receptors, has a potential effect on atrial muscarinic receptor-activated IKA ch current. In the present study, hearts of Rgs5 knockout (KO) mice had decreased low-frequency/high-frequency ratio in spectral measures of heart rate variability. Loss of Rgs5 provoked dramatically exaggerated bradycardia and significantly (P<0.05) prolonged sinus nodal recovery time in response to carbachol (0.1 mg/kg, intraperitoneally). Compared to those from wild-type (WT) mice, Langendorff perfused hearts from Rgs5 KO mice had significantly (P<0.01) abbreviated atrial effective refractory periods and increased dominant frequency after administration of acetylcholine (ACh; 1 μmol/L). In addition, whole patch clamp analyses of single atrial myocytes revealed that the ACh-regulated potassium current (IKA ch) was significant increased in the time course of activation and deactivation (P<0.01) in Rgs5 KO, compared to those in WT, mice. To further determine the effect of Rgs5, transgenic mice with cardiac-specific overexpression of human Rgs5 were found to be resistant to ACh-related effects in bradycardia, atrial electrophysiology, and atrial tachyarrhythmia (AT). The results of this study indicate that, as a critical regulator of parasympathetic activation in the heart, Rgs5 prevents vagal-related bradycardia and AT through negatively regulating the IKA ch current. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for the Treatment of Obesity in the ReCharge Trial.

    PubMed

    Apovian, Caroline M; Shah, Sajani N; Wolfe, Bruce M; Ikramuddin, Sayeed; Miller, Christopher J; Tweden, Katherine S; Billington, Charles J; Shikora, Scott A

    2017-01-01

    The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes. Participants with body mass index (BMI) 40 to 45 kg/m 2 , or 35 to 40 kg/m 2 with at least one comorbid condition were randomized to either vBloc therapy or sham intervention for 12 months. After 12 months, participants randomized to vBloc continued open-label vBloc therapy and are the focus of this report. Weight loss, adverse events, comorbid risk factors, and quality of life (QOL) will be assessed for 5 years. At 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (-16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (-46 mg/dL), HbA1c (-0.3 %), and systolic (-11 mmHg) and diastolic blood pressures (-10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %. vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years. https://clinicaltrials.gov/ct2/show/NCT01327976.

  9. Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

    PubMed

    Kim, Ji-Il; Cho, Hye-Yeon; Han, Jin-Hee; Kaang, Bong-Kiun

    2016-04-01

    During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression.

  10. Which Neurons Will Be the Engram - Activated Neurons and/or More Excitable Neurons?

    PubMed Central

    Kim, Ji-il; Cho, Hye-Yeon; Han, Jin-Hee

    2016-01-01

    During past decades, the formation and storage principle of memory have received much attention in the neuroscience field. Although some studies have attempted to demonstrate the nature of the engram, elucidating the memory engram allocation mechanism was not possible because of the limitations of existing methods, which cannot specifically modulate the candidate neuronal population. Recently, the development of new techniques, which offer ways to mark and control specific populations of neurons, may accelerate solving this issue. Here, we review the recent advances, which have provided substantial evidence showing that both candidates (neuronal population that is activated by learning, and that has increased CREB level/excitability at learning) satisfy the criteria of the engram, which are necessary and sufficient for memory expression. PMID:27122991

  11. An investigation into the relative merits of pituitary adenylate cyclase-activating polypeptide (PACAP-27) and vasoactive intestinal polypeptide as vagal neuro-transmitters in exocrine pancreas of rats.

    PubMed

    Wheeler, S; Eardley, J E; McNulty, K F; Sutcliffe, C P; Morrison, J D

    1997-07-01

    Pancreatic exocrine secretions were collected over 15 min periods and analysed in terms of weight of juice, total HCO3- and total protein in anaesthetized and pithed rats. Pituitary adenylate cyclase-activating polypeptide (PACAP) (i.v.) evoked a serous HCO3- secretion which contained relatively little protein, together with a marked vasodepressor action. The latter was still maximal at lower doses of PACAP, which evoked diminished pancreatic secretions. The effects of PACAP were similar to those evoked by the same dose of VIP and by cervical vagal stimulation, while secretion evoked a much larger secretion of fluid and HCO3-. The time courses of the PACAP-evoked secretions were significantly delayed compared with those of VIP. In the pithed rat, PACAP caused the same level of pancreatic secretions as in the anaesthetized rat, though this was now accompanied by a substantial pressor response which was blocked by phentolamine or prazosin, indicating that it was alpha 1-adrenoceptor mediated. VIP caused a depressor response in the pithed rat, as well as the same level of pancreatic secretions as in the anaesthetized rat. The putative VIP antagonist [Lys1,Pro25,Arg3,4,Tyr6]-VIP (abbreviated as VIPi) caused a selective and significant reduction in the HCO3- secretion evoked by VIP and blocked the vasodepressor response caused by VIP. By contrast, VIPi did not antagonize either the secretory or vasodepressor actions of PACAP. Unilateral electrical stimulation of the cervical vagus nerve evoked significant increases in the weight of juice, total protein and total HCO3- secreted. When preceded by injection of VIPi, vagally evoked secretions were unchanged in terms of weight of juice and total protein but had a significantly reduced HCO3- content. These results are consistent with the release of VIP, though not PACAP, as a vagal neurotransmitter in the exocrine pancreas.

  12. Uncovering Neuronal Networks Defined by Consistent Between-Neuron Spike Timing from Neuronal Spike Recordings

    PubMed Central

    2018-01-01

    Abstract It is widely assumed that distributed neuronal networks are fundamental to the functioning of the brain. Consistent spike timing between neurons is thought to be one of the key principles for the formation of these networks. This can involve synchronous spiking or spiking with time delays, forming spike sequences when the order of spiking is consistent. Finding networks defined by their sequence of time-shifted spikes, denoted here as spike timing networks, is a tremendous challenge. As neurons can participate in multiple spike sequences at multiple between-spike time delays, the possible complexity of networks is prohibitively large. We present a novel approach that is capable of (1) extracting spike timing networks regardless of their sequence complexity, and (2) that describes their spiking sequences with high temporal precision. We achieve this by decomposing frequency-transformed neuronal spiking into separate networks, characterizing each network’s spike sequence by a time delay per neuron, forming a spike sequence timeline. These networks provide a detailed template for an investigation of the experimental relevance of their spike sequences. Using simulated spike timing networks, we show network extraction is robust to spiking noise, spike timing jitter, and partial occurrences of the involved spike sequences. Using rat multineuron recordings, we demonstrate the approach is capable of revealing real spike timing networks with sub-millisecond temporal precision. By uncovering spike timing networks, the prevalence, structure, and function of complex spike sequences can be investigated in greater detail, allowing us to gain a better understanding of their role in neuronal functioning. PMID:29789811

  13. [The ontogeny of the mirror neuron system].

    PubMed

    Myowa-Yamakoshi, Masako

    2014-06-01

    Abstract Humans utilize the mirror neuron system to understand and predict others' actions. However, the ontogeny of the mirror neuron system remains unknown. Whether mirror neuron function is an innate trait or whether mirror neurons acquire their sensorimotor matching properties ontogenetically remains to be clarified. In this paper, I review the ontogenetic theory of the mirror neuron system. I then discuss the functioning of the mirror neuron system in the context of social cognitive abilities, which are unique to humans. Recently, some researchers argue that it is too early to interpret the function of mirror neurons as an understanding of the underlying psychological states of others. They imply that such functioning would require inferential cognitive processes that are known to involve areas outside the mirror neuron system. Filling in this missing link may be the key to elucidating the unique ability of humans to understand others' actions.

  14. The Neuronal Infrastructure of Speaking

    ERIC Educational Resources Information Center

    Menenti, Laura; Segaert, Katrien; Hagoort, Peter

    2012-01-01

    Models of speaking distinguish producing meaning, words and syntax as three different linguistic components of speaking. Nevertheless, little is known about the brain's integrated neuronal infrastructure for speech production. We investigated semantic, lexical and syntactic aspects of speaking using fMRI. In a picture description task, we…

  15. Biomechanics of Single Cortical Neurons

    PubMed Central

    Bernick, Kristin B.; Prevost, Thibault P.; Suresh, Subra; Socrate, Simona

    2011-01-01

    This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude – 10, 1, and 0.1 μm/s. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper-) elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. PMID:20971217

  16. Hypothalamic neurones governing glucose homeostasis.

    PubMed

    Coppari, R

    2015-06-01

    The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

  17. Optimal compensation for neuron loss

    PubMed Central

    Barrett, David GT; Denève, Sophie; Machens, Christian K

    2016-01-01

    The brain has an impressive ability to withstand neural damage. Diseases that kill neurons can go unnoticed for years, and incomplete brain lesions or silencing of neurons often fail to produce any behavioral effect. How does the brain compensate for such damage, and what are the limits of this compensation? We propose that neural circuits instantly compensate for neuron loss, thereby preserving their function as much as possible. We show that this compensation can explain changes in tuning curves induced by neuron silencing across a variety of systems, including the primary visual cortex. We find that compensatory mechanisms can be implemented through the dynamics of networks with a tight balance of excitation and inhibition, without requiring synaptic plasticity. The limits of this compensatory mechanism are reached when excitation and inhibition become unbalanced, thereby demarcating a recovery boundary, where signal representation fails and where diseases may become symptomatic. DOI: http://dx.doi.org/10.7554/eLife.12454.001 PMID:27935480

  18. Neuronal migration on laminin in vitro.

    PubMed

    Liang, S; Crutcher, K A

    1992-03-20

    Chick sympathetic (E-9) or telencephalic (E-7) neurons were cultured at low density on poly-DL-ornithine (PORN), poly-L-lysine (POLS), laminin or laminin-covered PORN or POLS and monitored with time-lapse videomicroscopy. Neurons migrated on laminin, or laminin-covered PORN or POLS, but not on PORN or POLS alone. Neuronal migration did not involve interactions with other cells indicating that neurons are capable of independent migration when exposed to a laminin substrate.

  19. Spiking neuron network Helmholtz machine.

    PubMed

    Sountsov, Pavel; Miller, Paul

    2015-01-01

    An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule.

  20. Spiking neuron network Helmholtz machine

    PubMed Central

    Sountsov, Pavel; Miller, Paul

    2015-01-01

    An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule. PMID:25954191

  1. Neuronal imprinting of human values.

    PubMed

    Delgado, J M

    2000-03-01

    In the 21st century, psychophysiology will face the challenge of establishing ethical principles and practical means for the genetic and social influencing of the development of human beings. Neuronal imprinting of beliefs and morality within infantile minds will be necessary for the peaceful coexistence of races and cultures. This process requires study and consideration, among others, of the following psychophysiological facts: (1) Genes do not transmit moral values. (2) Material support of physiological activities is necessary for the existence and development of mental functions. (3) Imprinting of human values is based on material changes within neuronal structures. (4) Early neuronal imprinting is performed without personal awareness or consent of the individual and depends on sensory inputs, mainly from the social structure of the group. (5) Biological structures lack values. Personal and social antagonisms do not depend on genes, but on cultural indoctrination. (6) Pleasure and punishment (positive and negative reinforcement) are the two main elements, which regulate animal and human behavior. (7) Values must be chosen by adults, who decide the questions 'why'? 'when'? 'which ones'?, 'who should teach'?, 'what?' and 'how'? (8) Many biological imperatives are shared by all animals and by all people. Human beings may be considered the 'crickets of the Universe', unable to understand the mysteries of nature because of our insufficient neuronal capacity. (9) Our emotional life is mainly related to the structure of the limbic system controlled by the neocortex. (10) New theories based on the integration of physics, chemistry, biology and other specific areas of knowledge, as proposed by the General Theory of Systems, will avoid 'opposites', favoring the acceptance of complementary aspects of reality. (11) Early education will promote preferential learning which depends on both genetic endowment and neuronal development influenced by experience. It is the

  2. Prospective Coding by Spiking Neurons

    PubMed Central

    Brea, Johanni; Gaál, Alexisz Tamás; Senn, Walter

    2016-01-01

    Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron’s firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ). PMID:27341100

  3. BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

    PubMed

    Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

    2015-10-01

    Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

  4. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    PubMed

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (p<0.05). Human dentate nucleus neurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short

  5. Foxp2 regulates neuronal differentiation and neuronal subtype specification.

    PubMed

    Chiu, Yi-Chi; Li, Ming-Yang; Liu, Yuan-Hsuan; Ding, Jing-Ya; Yu, Jenn-Yah; Wang, Tsu-Wei

    2014-07-01

    Mutations of the transcription factor FOXP2 in humans cause a severe speech and language disorder. Disruption of Foxp2 in songbirds or mice also leads to deficits in song learning or ultrasonic vocalization, respectively. These data suggest that Foxp2 plays important roles in the developing nervous system. However, the mechanism of Foxp2 in regulating neural development remains elusive. In the current study, we found that Foxp2 increased neuronal differentiation without affecting cell proliferation and cell survival in primary neural progenitors from embryonic forebrains. Foxp2 induced the expression of platelet-derived growth factor receptor α, which mediated the neurognic effect of Foxp2. In addition, Foxp2 positively regulated the differentiation of medium spiny neurons derived from the lateral ganglionic eminence and negatively regulated the formation of interneurons derived from dorsal medial ganglionic eminence by interacting with the Sonic hedgehog pathway. Taken together, our results suggest that Foxp2 regulates multiple aspects of neuronal development in the embryonic forebrain. © 2014 Wiley Periodicals, Inc.

  6. What We Know Currently about Mirror Neurons

    PubMed Central

    Kilner, J.M.; Lemon, R.N.

    2013-01-01

    Mirror neurons were discovered over twenty years ago in the ventral premotor region F5 of the macaque monkey. Since their discovery much has been written about these neurons, both in the scientific literature and in the popular press. They have been proposed to be the neuronal substrate underlying a vast array of different functions. Indeed so much has been written about mirror neurons that last year they were referred to, rightly or wrongly, as “The most hyped concept in neuroscience”. Here we try to cut through some of this hyperbole and review what is currently known (and not known) about mirror neurons. PMID:24309286

  7. Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

    PubMed

    Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

    2012-08-22

    In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Cardiac neuronal hierarchy in health and disease.

    PubMed

    Armour, J Andrew

    2004-08-01

    The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.

  9. Dendrites of medial olivocochlear neurons in mouse.

    PubMed

    Brown, M C; Levine, J L

    2008-06-12

    Stains for acetylcholinesterase (AChE) and retrograde labeling with Fluorogold (FG) were used to study olivocochlear neurons and their dendritic patterns in mice. The two methods gave similar results for location and number of somata. The total number of medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body (VNTB) is about 170 per side. An additional dozen large olivocochlear neurons are located in the dorsal periolivary nucleus (DPO). Dendrites of all of these neurons are long and extend in all directions from the cell bodies, a pattern that contrasts with the sharp frequency tuning of their responses. For VNTB neurons, there were greater numbers of dendrites directed medially than laterally and those directed medially were longer (on average, 25-50% longer). Dendrite extensions were most pronounced for neurons located in the rostral portion of the VNTB. When each dendrite from a single neuron was represented as a vector, and all the vectors summed, the result was also skewed toward the medial direction. DPO neurons, however, had more symmetric dendrites that projected into more dorsal parts of the trapezoid body, suggesting that this small group of olivocochlear neurons has very different physiological properties. Dendrites of both types of neurons were somewhat elongated rostrally, about 20% longer than those directed caudally. These results can be interpreted as extensions of dendrites of olivocochlear neurons toward their synaptic inputs: medially to meet crossing fibers from the cochlear nucleus that are part of the MOC reflex pathway, and rostrally to meet descending inputs from higher centers.

  10. Neuronal Allocation to a Hippocampal Engram

    PubMed Central

    Park, Sungmo; Kramer, Emily E; Mercaldo, Valentina; Rashid, Asim J; Insel, Nathan; Frankland, Paul W; Josselyn, Sheena A

    2016-01-01

    The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation. PMID:27187069

  11. Neuronal Allocation to a Hippocampal Engram.

    PubMed

    Park, Sungmo; Kramer, Emily E; Mercaldo, Valentina; Rashid, Asim J; Insel, Nathan; Frankland, Paul W; Josselyn, Sheena A

    2016-12-01

    The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation.

  12. How to make spinal motor neurons.

    PubMed

    Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

    2014-02-01

    All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

  13. Large-scale recording of neuronal ensembles.

    PubMed

    Buzsáki, György

    2004-05-01

    How does the brain orchestrate perceptions, thoughts and actions from the spiking activity of its neurons? Early single-neuron recording research treated spike pattern variability as noise that needed to be averaged out to reveal the brain's representation of invariant input. Another view is that variability of spikes is centrally coordinated and that this brain-generated ensemble pattern in cortical structures is itself a potential source of cognition. Large-scale recordings from neuronal ensembles now offer the opportunity to test these competing theoretical frameworks. Currently, wire and micro-machined silicon electrode arrays can record from large numbers of neurons and monitor local neural circuits at work. Achieving the full potential of massively parallel neuronal recordings, however, will require further development of the neuron-electrode interface, automated and efficient spike-sorting algorithms for effective isolation and identification of single neurons, and new mathematical insights for the analysis of network properties.

  14. Mirror neurons and motor intentionality.

    PubMed

    Rizzolatti, Giacomo; Sinigaglia, Corrado

    2007-01-01

    Our social life rests to a large extent on our ability to understand the intentions of others. What are the bases of this ability? A very influential view is that we understand the intentions of others because we are able to represent them as having mental states. Without this meta-representational (mind-reading) ability their behavior would be meaningless to us. Over the past few years this view has been challenged by neurophysiological findings and, in particular, by the discovery of mirror neurons. The functional properties of these neurons indicate that intentional understanding is based primarily on a mechanism that directly matches the sensory representation of the observed actions with one's own motor representation of those same actions. These findings reveal how deeply motor and intentional components of action are intertwined, suggesting that both can be fully comprehended only starting from a motor approach to intentionality.

  15. Neuronal network models of epileptogenesis

    PubMed Central

    Abdullahi, Aminu T.; Adamu, Lawan H.

    2017-01-01

    Epilepsy is a chronic neurological condition, following some trigger, transforming a normal brain to one that produces recurrent unprovoked seizures. In the search for the mechanisms that best explain the epileptogenic process, there is a growing body of evidence suggesting that the epilepsies are network level disorders. In this review, we briefly describe the concept of neuronal networks and highlight 2 methods used to analyse such networks. The first method, graph theory, is used to describe general characteristics of a network to facilitate comparison between normal and abnormal networks. The second, dynamic causal modelling, is useful in the analysis of the pathways of seizure spread. We concluded that the end results of the epileptogenic process are best understood as abnormalities of neuronal circuitry and not simply as molecular or cellular abnormalities. The network approach promises to generate new understanding and more targeted treatment of epilepsy. PMID:28416779

  16. Oscillatory integration windows in neurons

    PubMed Central

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-01-01

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking. PMID:27976720

  17. Unbalanced neuronal circuits in addiction.

    PubMed

    Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D

    2013-08-01

    Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it. Published by Elsevier Ltd.

  18. DNA Damage Induced Neuronal Death

    DTIC Science & Technology

    1999-10-01

    heterozygous for the DNA repair genes Os-methylguanine methyltransferase (Mgmt), 3-methyladenine DNA glycosylase (Aag) , and xeroderma pigmentosum ...mice by human 06-alkylguanine-DNA alkyltransferase. Science 1993; 259: 219-222. 4. Enokido Y, Inamura N, Araki T, et al: Loss of the xeroderma ... pigmentosum group A gene (XPA) enhances apoptosis of cultured cerebellar neurons induced by UV but not by low-K+ medium. J Neurochem 199; 69: 246-251. 5

  19. Neurochemical phenotypes of cardiorespiratory neurons.

    PubMed

    Pilowsky, Paul M

    2008-12-10

    Interactions between the cardiovascular and respiratory systems have been known for many years but the functional significance of the interactions is still widely debated. Here I discuss the possible role of metabotropic receptors in regulating cardiorespiratory neurons in the brainstem and spinal cord. It is clear that, although much has been discovered, cardiorespiratory regulation is certainly one area that still has a long way to go before its secrets are fully divulged and their function in controlling circulatory and respiratory function is revealed.

  20. Guiding neuronal growth with light

    PubMed Central

    Ehrlicher, A.; Betz, T.; Stuhrmann, B.; Koch, D.; Milner, V.; Raizen, M. G.; Käs, J.

    2002-01-01

    Control over neuronal growth is a fundamental objective in neuroscience, cell biology, developmental biology, biophysics, and biomedicine and is particularly important for the formation of neural circuits in vitro, as well as nerve regeneration in vivo [Zeck, G. & Fromherz, P. (2001) Proc. Natl. Acad. Sci. USA 98, 10457–10462]. We have shown experimentally that we can use weak optical forces to guide the direction taken by the leading edge, or growth cone, of a nerve cell. In actively extending growth cones, a laser spot is placed in front of a specific area of the nerve's leading edge, enhancing growth into the beam focus and resulting in guided neuronal turns as well as enhanced growth. The power of our laser is chosen so that the resulting gradient forces are sufficiently powerful to bias the actin polymerization-driven lamellipodia extension, but too weak to hold and move the growth cone. We are therefore using light to control a natural biological process, in sharp contrast to the established technique of optical tweezers [Ashkin, A. (1970) Phys. Rev. Lett. 24, 156–159; Ashkin, A. & Dziedzic, J. M. (1987) Science 235, 1517–1520], which uses large optical forces to manipulate entire structures. Our results therefore open an avenue to controlling neuronal growth in vitro and in vivo with a simple, noncontact technique. PMID:12456879