Parasympathetic Mechanisms Research Articles

Genetic and Functional Identification of Cardiovagal Nucleus Ambiguus Neurons

Heart rate is an important physiological index of overall health and is primarily controlled by the parasympathetic nervous system, which suppresses heart rate at rest and during cardiac reflexes. The nucleus ambiguus (nAmb), a region found within the brainstem, is a primary source of parasympathetic input to the heart. It also innervates striated muscles of the larynx, pharynx, and esophagus to regulate the motor function of speech and swallowing. To identify candidate cardiovagal neurons and differentiate them from neighboring motor neurons, we profiled genome-wide RNA expression in ~1,250 nAmb neurons by single nuclei RNA-sequencing. Clustering these neurons based on their transcriptomic similarity revealed six candidate molecular subtypes, which we annotated according to their subtype-specific marker genes. Based on their gene expression profiles, we hypothesized that three subtypes may be cardiovagal neurons. Three other subtypes, marked by Vipr2 or Crhr2 expression, likely correspond to the neurons that innervate the upper airways and esophagus, as shown by our previous work. Two of the three potential cardiovagal subtypes were specifically marked by their expression of Vip and Adcyap1, respectively, and the other subtype co-expressed Npy2r and Adcyap1. Fluorescence RNA in situ hybridization validated that Npy2r and Adcyap1 transcripts mark partially overlapping nAmb neurons residing throughout its rostrocaudal axis. To determine whether these neuron subtypes can control heart rate, we targeted expression of a calcium-translocating channelrhodopsin variant (CatCh) to the Npy2r+ and Adcyap1+ nAmb neuron subtypes using intersectional genetics. We then activated CatCh+ neuron subtypes using laser light transmitted via a fiber optic implanted over the nAmb and measured the effect on heart rate (HR) in awake, behaving mice. Our results show an immediate and dramatic decrease in HR upon activation of Npy2r+nAmb neurons (n=6 Npy2r-Cre:Chat-Flp:CatCh mice; laser-on HR= 58 ± 17% of laser-off HR; p<0.0001), or Adcyap1+nAmb neurons (n=5 Adcyap1-Cre:Chat-Flp:CatCh mice; laser-on HR= 34 ± 13% of laser-off HR; p<0.0001). The HR decrease depended on the frequency of stimulation (n=3 mice per genotype) and was not observed in the absence of CatCh expression (n=4 mice; laser-on HR = 100 ± 0% of laser-off HR; p>0.05). Blocking muscarinic receptors with atropine prevented the bradycardic effect of activating Npy2r+nAmb neurons (n=5 mice), suggesting a parasympathetic mechanism. These results indicate that Npy2r+nAmb neurons and Adcyap1+nAmb neurons are capable of suppressing HR, which builds on our previous observation of bradycardia when activating all nAmb neurons but not when activating the upper airway and esophageal projecting subtypes (recently published) Vipr2+nAmb neurons and Crhr2+nAmb neurons, respectively. Together, our results identify cardiovagal neuron subtypes in the nAmb based on their molecular and functional properties. The authors gratefully acknowledge Maisie Crook for her technical assistance. Funding was provided by National Institutes for Health (NIH) F31 HL158187 to T.C.C.; NIH R01 HL148004 to S.B.G.A.; and an American Diabetes Association Pathway to Stop Diabetes Initiator Award 1-18-INI-14 and NIH R01 HL153916 to J.N.C. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Characterizing cardiac autonomic dynamics of fear learning in humans.

Understanding transient dynamics of the autonomic nervous system during fear learning remains a critical step to translate basic research into treatment of fear-related disorders. In humans, it has been demonstrated that fear learning typically elicits transient heart rate deceleration. However, classical analyses of heart rate variability (HRV) fail to disentangle the contribution of parasympathetic and sympathetic systems, and crucially, they are not able to capture phasic changes during fear learning. Here, to gain deeper insight into the physiological underpinnings of fear learning, a novel frequency-domain analysis of heart rate was performed using a short-time Fourier transform, and instantaneous spectral estimates extracted from a point-process modeling algorithm. We tested whether spectral transient components of HRV, used as a noninvasive probe of sympathetic and parasympathetic mechanisms, can dissociate between fear conditioned and neutral stimuli. We found that learned fear elicited a transient heart rate deceleration in anticipation of noxious stimuli. Crucially, results revealed a significant increase in spectral power in the high frequency band when facing the conditioned stimulus, indicating increased parasympathetic (vagal) activity, which distinguished conditioned and neutral stimuli during fear learning. Our findings provide a proximal measure of the involvement of cardiac vagal dynamics into the psychophysiology of fear learning and extinction, thus offering new insights for the characterization of fear in mental health and illness.

Parasympathetic innervation contributes to the increase of survival rate and anti-inflammatory effect of electroacupuncture at "Ciliao"(BL32) in rats with lethal endotoxemia

To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) on the survival rate and serum inflammatory cytokine levels in rats with lethal endotoxemia, and to explore its parasympathetic mechanism in suppressing severe systemic inflammation. A total of 82 male SD rats were used in the present study. In the first part of this study, 40 rats were randomized into model and EA-BL32 groups (n=20/group). The endotoxemia model was established by intraperitoneal injection of lethal amount of lipopolysaccharide (LPS, 10 mg/kg). EA (30 Hz, 6 mA) was applied to bilateral BL32 for 30 min before and after LPS injection. The survival rate in 7 days was then recorded. In the second part of this study, 42 rats were randomized into normal control, model, EA-BL32, EA-BL32+cervical vagotomy, EA-BL32+truncal (subdiagrammatical) vagotomy and EA-BL32+pelvic neurectomy groups (n=7/group). The endotoxemia model was established by intraperitoneal injection of LPS (6 mg/kg) 30 min after the neurectomy. Rats of the control group received intraperitoneal injection of 6 mg/kg saline. EA with the same parameters mentioned above was applied to bilateral BL32 for 30 min before and after LPS injection. Blood sample was collected from the abdominal aorta 3 h after LPS injection for detecting the levels of TNF-α, IL-1β and IL-6 by ELISA. ① The EA survival rate was 25% in the model group and 60% in the EA -BL32group, being significantly improved after EA (P<0.05). ② The contents of serum TNF-α, IL-1β and IL-6 were significantly higher in the model group than those in the control group (P<0.000 1). After EA intervention, and compared with the model group, the levels of TNF-α, IL-1β and IL-6 were significantly decreased in the EA-BL32, EA-BL32+cervical vagotomy, EA-BL32+truncal vagotomy and EA-BL32+pelvic neurectomy groups (P<0.000 1，P<0.01). After neurectomy and compared to the EA-BL32 group, the contents of TNF-α and IL-6 in the EA+cervical vagotomy and EA+pelvic neurectomy groups, IL-1β in the EA+pelvic neurotomy group were significantly higher (P<0.0000 1, P<0.05), suggesting an elimination of EA effects after neurectomy. No significant differences were found among the 3 neurectomy groups in the levels of TNF-α, IL-1β and IL-6 (P>0.05). EA of BL32 can improve the survival rate and attenuate the level of inflammatory cytokines in rats with lethal endotoxemia, which is closely related to the intact of parasympathetic pathway including the vagus nerve and pelvic nerve.

Neurogenic dysfunction of the lower urinary tract (neurogenic bladder)

The lecture presents information about the central and peripheral structures that provide innervation and regulation of the functions of the lower urinary tract — the bladder and urethra. The mechanisms of regulation of the functions of accumulation and retention of urine (reservoir function) and emptying of the bladder (evacuation function) are shown.Neural control of urination is organized in the form of a hierarchical system. The spinal centers are the executive structures, and the cerebral centers are the controlling structures. Involuntary implementation of the act of urination occurs through segmental sympathetic and parasympathetic mechanisms. The regulation of these functions and voluntary urination are carried out by the central mechanisms of the brain — the actuation of the urination reflex is under strict volitional control, which makes it possible to plan the emptying of the bladder in a socially acceptable place and time.The information on the clinical symptoms of neurogenic dysfunction of the lower urinary tract (neurogenic bladder) is reviewed. The features of clinical manifestations depending on the level of damage to neural structures and in various neurological diseases are shown. Methods for assessing urodynamics and treatment directions for neurogenic dysfunction of the lower urinary tract are presented.

Fibroblast Growth Factor 19 Increases the Excitability of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice.

Intracerebroventricular administration of the protein hormone fibroblast growth factor 19 (FGF19) to the hindbrain produces potent antidiabetic effects in hyperglycemic mice that are likely mediated through a vagal parasympathetic mechanism. FGF19 increases the synaptic excitability of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) from hyperglycemic, but not normoglycemic, mice but the source of this synaptic input is unknown. Neurons in the area postrema (AP) and nucleus tractus solitarius (NTS) express high levels of FGF receptors and exert glutamatergic control over the DMV. This study tested the hypothesis that FGF19 increases glutamate release in the DMV by increasing the activity of glutamatergic AP and NTS neurons in hyperglycemic mice. Glutamate photoactivation experiments confirmed that FGF19 increases synaptic glutamate release from AP and NTS neurons that connect to the DMV in hyperglycemic, but not normoglycemic mice. Contrary to expectations, FGF19 produced a mixed effect on intrinsic membrane properties in the NTS with a trend towards inhibition, suggesting that another mechanism was responsible for the observed effects on glutamate release in the DMV. Consistent with the hypothesis, FGF19 increased action potential-dependent glutamate release in the NTS in hyperglycemic mice only. Finally, glutamate photoactivation experiments confirmed that FGF19 increases the activity of glutamatergic AP neurons that project to the NTS in hyperglycemic mice. Together, these results support the hypothesis that FGF19 increases glutamate release from AP and NTS neurons that project to the DMV in hyperglycemic mice. FGF19 therefore modifies the local vago-vagal reflex circuitry at several points. Additionally, since the AP and NTS communicate with several other metabolic regulatory nuclei in the brain, FGF19 in the hindbrain may alter neuroendocrine and behavioral aspects of metabolism, in addition to changes in parasympathetic output.

Efficacy of relative bronchodilatation of salbutamol and ipratropium in smokers and non-smokers with asthma

Asthma is an age old disease with breathlessness and wheezing as a part of its clinical manifestations. Adrenergic drugs are also used as bronchodilators as they have a fast action. They are also useful in improving the mucilary transport and in the reduction in the release of inflammatory mediators. Sympathetic and parasympathetic mechanisms for airway calibre control were tested on 80 patients above the age of 18 years with bronchial asthma using salbutamol (beta 2 androgenic drug) and ipratropium bromide (anticholinergic drug). The base line values in our study, of the smokers and non-smokers on Day 1, where Salbutamol was given as the primary drug with Ipratropium as the second drug showed a significant difference in the FEV1, FVC and PEFR values, while there was no significant difference in the FEV1/FVC ratio. After giving salbutamol to the maximum effect, in comparison to the base line, there was a considerable improvement in all the values in both the smokers and non-smokers. But on giving Ipratropium, there was no further substantial improvement in the values in the non-smokers, but a significant improvement was seen among the smokers. On day two, there was a significant improvement in the FEV1, FVC, FEV1/FVC and PEFR values compared to the base line values, and on giving salbutamol, there was a substantial increase in the expiration volume in both smokers and non-smokers. In case of smoker asthmatics, a combination therapy of Salbutamol and Ipratropium is more useful.

Baroreflex responses during dry resting and exercise apnoeas in air and pure oxygen

PurposeWe analysed the characteristics of arterial baroreflexes during the first phase of apnoea (φ1).Methods12 divers performed rest and exercise (30 W) apnoeas (air and oxygen). We measured beat-by-beat R-to-R interval (RRi) and mean arterial pressure (MAP). Mean RRi and MAP values defined the operating point (OP) before (PRE-ss) and in the second phase (φ2) of apnoea. Baroreflex sensitivity (BRS, ms·mmHg−1) was calculated with the sequence method.ResultsIn PRE-ss, BRS was (median [IQR]): at rest, 20.3 [10.0–28.6] in air and 18.8 [13.8–25.2] in O2; at exercise 9.2[8.4–13.2] in air and 10.1[8.4–13.6] in O2. In φ1, during MAP decrease, BRS was lower than in PRE-ss at rest (6.6 [5.3–11.4] in air and 7.7 [4.9–14.3] in O2, p < 0.05). At exercise, BRS in φ1 was 6.4 [3.9–13.1] in air and 6.7 [4.1–9.5] in O2. After attainment of minimum MAP (MAPmin), baroreflex resetting started. After attainment of minimum RRi, baroreflex sequences reappeared. In φ2, BRS at rest was 12.1 [9.6–16.2] in air, 12.9 [9.2–15.8] in O2. At exercise (no φ2 in air), it was 7.9 [5.4–10.7] in O2. In φ2, OP acts at higher MAP values.ConclusionIn apnoea φ1, there is a sudden correction of MAP fall via baroreflex. The lower BRS in the earliest φ1 suggests a possible parasympathetic mechanism underpinning this reduction. After MAPmin, baroreflex resets, displacing its OP at higher MAP level; thus, resetting may not be due to central command. After resetting, restoration of BRS suggests re-establishment of vagal drive.

Abstract WP377: Heart Rate Variability Biofeedback Improves Cardiac Autonomic Function in Patients With Acute Ischaemic Stroke: A Randomized Controlled Study

Introduction: In patients with acute ischaemic stroke (AIS) dysregulation of cardiac function with decreased heart rate variability (HRV) due to impaired integrity of the autonomic nervous system is a frequent complication which is associated with increased mortality and worsening of clinical outcome. HRV biofeedback has previously been suggested to improve cardiac autonomic function by increasing parasympathetic tone. Hypothesis: We hypothesized that HRV biofeedback can be used to complement stroke unit care and alleviate autonomic cardiac dysfunction following AIS. Methods: We randomly allocated patients with AIS to either receive 9 sessions of HRV (n=24) or sham (n=24) biofeedback in addition to standard stroke unit care. These patients underwent detailed assessment of autonomic cardiac function including analysis of HRV via standard deviation of NN intervals (SDNN) and spectral analysis. Furthermore, we assessed vasomotor and sudomotor autonomic function, severity of autonomic symptoms and neurological and functional outcomes. Results: We included 48 patients (19 females, ages 65±14 years, baseline NIHSS 2.2 ± 2.2, mean ± standard deviation). Patients who had undergone HRV biofeedback displayed improved cardiac function compared to baseline (SDNN 72.6 ± 52.4 ms vs. 45.5 ± 34.7 ms, p&lt;0.01) which was not seen in those who received sham biofeedback (p=ns). Similar changes were seen on spectral analysis measures of parasympathetic function (p&lt;0.01). Improvement of autonomic cardiac function following HRV biofeedback was paralleled by decreased severity of autonomic symptoms (p&lt;0.05). Contrasting our observation of an increase in predominantly parasympathetic parameters such as CVNN, sympathetic measures of sudomotor and vasomotor function remained unchanged in both groups (p=ns). Neurological and functional outcomes were unchanged immediately post intervention, however 3-month follow up is yet to be completed. Discussion: HRV biofeedback can modulate autonomic cardiac function post AIS to increase HRV and alleviate autonomic symptoms which might be beneficial in facilitating recovery from functional impairment. This seems to be mediated by a predominantly parasympathetic mechanism of action.

Autonomic influences on heart rate during marital conflict: Associations with high frequency heart rate variability and cardiac pre-ejection period

Psychosocial factors predict the development and course of cardiovascular disease, perhaps through sympathetic and parasympathetic mechanisms. At rest, heart rate (HR) is under parasympathetic control, often measured as high-frequency heart rate variability (HF-HRV). During stress, HR is influenced jointly by parasympathetic and sympathetic processes, the latter often quantified as pre-ejection period (PEP). In studies of cardiovascular risk factors that involve social interaction (e.g. marital conflict), HF-HRV might be altered by speech artifacts, weakening its validity as a measure of parasympathetic activity. To evaluate this possibility, we tested associations of HF-HRV and PEP with HR at rest and across periods of marital conflict interaction that varied in experimentally-manipulated degrees of speech in 104 couples. At rest, only HF-HRV was independently related to HR, for both husbands and wives. During speaking, listening, and recovery periods, husbands’ and wives’ HF-HRV and PEP change independently predicted HR change. These findings support interpretation of HF-HRV as a parasympathetic index during stressful social interactions that may confer risk for cardiovascular disease.

Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning.

AimsAlthough the nature of the humoral factor which mediates cardioprotection established by remote ischaemic conditioning (RIc) remains unknown, parasympathetic (vagal) mechanisms appear to play a critical role. As the production and release of many gut hormones is modulated by the vagus nerve, here we tested the hypothesis that RIc cardioprotection is mediated by the actions of glucagon-like peptide-1 (GLP-1).Methods and resultsA rat model of myocardial infarction (coronary artery occlusion followed by reperfusion) was used. Remote ischaemic pre- (RIPre) or perconditioning (RIPer) was induced by 15 min occlusion of femoral arteries applied prior to or during the myocardial ischaemia. The degree of RIPre and RIPer cardioprotection was determined in conditions of cervical or subdiaphragmatic vagotomy, or following blockade of GLP-1 receptors (GLP-1R) using specific antagonist Exendin(9–39). Phosphorylation of PI3K/AKT and STAT3 was assessed. RIPre and RIPer reduced infarct size by ∼50%. In conditions of bilateral cervical or subdiaphragmatic vagotomy RIPer failed to establish cardioprotection. GLP-1R blockade abolished cardioprotection induced by either RIPre or RIPer. Exendin(9–39) also prevented RIPre-induced AKT phosphorylation. Cardioprotection induced by GLP-1R agonist Exendin-4 was preserved following cervical vagotomy, but was abolished in conditions of M3 muscarinic receptor blockade.ConclusionsThese data strongly suggest that GLP-1 functions as a humoral factor of remote ischaemic conditioning cardioprotection. This phenomenon requires intact vagal innervation of the visceral organs and recruitment of GLP-1R-mediated signalling. Cardioprotection induced by GLP-1R activation is mediated by a mechanism involving M3 muscarinic receptors.

Expression of messenger molecules and receptors in rat and human sphenopalatine ganglion indicating therapeutic targets.

BackgroundMigraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters pituitary adenylate cyclase activating polypeptide (PACAP-38), nitric oxide synthase (nNOS), VIP and 5-hydroxttryptamine subtype receptors (5-HT1B,1D,1F) were examined.MethodsSPG from adult male rats and from humans, the later removed at autopsy, were prepared for immunohistochemistry using specific antibodies against neurotransmitters, 5-HT1B,1D,1F receptors, and botulinum toxin receptor elements.ResultsWe found that the selected neurotransmitters and 5-HT receptors were expressed in rat and human SPG. In addition, we found SV2-A and SNAP25 expression in both rat and human SPG. We report that all three 5-HT receptors studied occur in neurons and satellite glial cells (SGCs) of the SPG. 5-HT1B receptors were in addition found in the walls of intraganglionic blood vessels.ConclusionsRecent focus on the SPG has emphasized the role of parasympathetic mechanisms in the pathophysiology of mainly CH. The development of next generation’s drugs and treatment of cranial parasympathetic symptoms, mediated through the SPG, can be modulated by treatment with BoNT-A and 5-HT receptor agonists.

Vagoglossopharyngeal neuralgia revealed through predominant digestive vagal manifestations. Case report and literature review

Vagoglossopharyngeal neuralgia is a rare pathology whose atypical forms, dominated by syncopal manifestations, are still rarer. Although the territory of the vagus nerve involves, beyond the cardiovascular system, the respiratory and the digestive systems, there is no report in literature of atypical forms other than syncopal. Therefore, the authors were prompted to report the case of a patient whose vagoglossopharyngeal neuralgia was predominantly revealed by digestive symptoms. A 58-year-old patient presented with stereotypical severe digestive disturbances including nausea, vomiting and diarrhoea. High definition cranial MRI showed a neurovascular conflict between the posterior inferior cerebellar artery and the IXth and Xth nerves, on the right side. A microsurgical decompression was carried out which confirmed the vascular compression and successful transposition of the artery. One year after the surgery, the patient was free from all painful and digestive symptoms. A survey of the literature did not find any reference to digestive symptoms together with the neuralgia; only a syncopal type of cardiac symptoms related to the parasympathetic nervous system were described. The hypothesis was that the revealing digestive symptoms are linked to a similar parasympathetic mechanism, implying the visceral component of the Xth cranial nerve.

Autonomic Modulation in Heart Failure: Ready for Prime Time?

It has been known for many decades that multiple abnormalities of the autonomic nervous system (ANS) are present in heart failure (HF). Moreover, many of the effective therapies currently used to treat HF have either direct or indirect effects on the ANS. While therapies that block over-activity of the sympathetic nervous system are now standard of care, much less well studied are therapies aimed at augmenting the parasympathetic nervous system. This review will cover recent and ongoing investigations targeting modulation of the ANS, especially highlighting new and ongoing studies directed toward augmenting parasympathetic mechanisms.

Study of Autonomic Functions in Cigarette Smokers

Introduction: Smoking is one of the most ancient and widespread mans activities. The present study was chosen to determine sympathetic and parasympathetic activity in cigarette smokers and compare it with healthy age matched controls in order to find out what influence does smoking have on baroreceptor sympathetic and parasympathetic control mechanisms and to find out for any co-relation between duration of cigarette smoking and autonomic dysfunction.Materials &amp; Methods: Fifty cigarette smokers and fifty normal, healthy, nonsmokers were selected as age matched controls to study autonomic functions. Sympathetic functions were carried out by Cold Pressor Response test and Hand Grip test. Parasympathetic functions were tested by Determination of Heart Rate with change in posture and Sinus Arrhythmia.Results: Smokers revealed more pronounced rise both in systolic as well as diastolic blood pressure as compared to normal healthy controls during cold pressor test. Smokers revealed more pronounced rise in both SBP and DBP as compared to nonsmokers during hand grip test. There was increased heart rate in initial 10 seconds when there is postural change i.e. lying down to standing in both the groups. There was an increase in heart rate during inspiration and decrease during expiration (sinus arrhythmia) both in smokers and healthy controls.Conclusion: Cigarette smoking affects cardiovascular functions as indicated by rise in blood pressure in smokers than nonsmokers reflects the sensitivity of sympathetic activity to nicotine due to smoking. Thus the study concludes that smoking possibly has an effect on neurocardiovascular regulation system altering the sensitivity of ANS activity in habitual smokers.Keywords: Autonomic Function Tests, Smokers, Non-smokers, Cold Pressor Test, Hand Grip Test, Heart Rate.

Associations between inhibitory control, respiratory sinus arrhythmia, and externalizing problems in early childhood

Polyvagal theory provides a framework for understanding connections between children's autonomic regulation, cognitive functioning, and behavioral adjustment. Parasympathetic regulation has been associated with executive functions and externalizing problems (EP), and children with EP demonstrate deficits in inhibition of prepotent responding, or inhibitory control (IC). We examined parasympathetic regulation of cardiac reactivity during two IC tasks in 144 children (M = 5.61 years, SD = 1.09) ranging from low to clinical levels of EP. Overall children with more EP evidenced greater RSA suppression during IC tasks than did children with fewer EP, and degree of RSA suppression also moderated associations between IC performance and EP. Only for children who showed stronger RSA suppression was accuracy of IC response inversely associated with EP, and latency of response for one task positively associated with EP. This study provides insight into the role of parasympathetic mechanisms in children's cognitive regulation of impulsive and aggressive behaviors.

Glutamate transporter type 3 knockout leads to decreased heart rate possibly via parasympathetic mechanism

Parasympathetic tone is a dominant neural regulator for basal heart rate. Glutamate transporters (EAAT) via their glutamate uptake functions regulate glutamate neurotransmission in the central nervous system. We showed that EAAT type 3 (EAAT3) knockout mice had a slower heart rate than wild-type mice when they were anesthetized. We design this study to determine whether non-anesthetized EAAT3 knockout mice have a slower heart rate and, if so, what may be the mechanism for this effect. Young adult EAAT3 knockout mice had slower heart rates than those of their littermate wild-type mice no matter whether they were awake or anesthetized. This difference was abolished by atropine, a parasympatholytic drug. Carbamylcholine chloride, a parasympathomimetic drug, equally effectively reduced the heart rates of wild-type and EAAT3 knockout mice. Positive immunostaining for EAAT3 was found in the area of nuclei deriving fibers for vagus nerve. There was no positive staining for the EAATs in the sinoatrial node. These results suggest that EAAT3 knockout mice have a slower heart rate at rest. This effect may be caused by an increased parasympathetic tone possibly due to increased glutamate neurotransmission in the central nervous system. These findings indicate that regulation of heart rate, a vital sign, is one of the EAAT biological functions.

Bronchorrhea following Stroke

Background: Stroke-induced excessive bronchial secretion is not rare, but seldom discussed. This study emphasizes its recognition, pathophysiology and treatment. Methods: We prospectively collected data from 19 consecutive stroke patients with bronchorrhea who were admitted within 2 days of stroke onset. Results: Sixteen of them (84%) suffered from ischemic stroke, and 3 patients (16%) had hemorrhage. All of them had brainstem involvement, and 11 of them (58%) had localized lesions in the dorsal lateral medulla. In 15 patients (79%), copious secretion developed within 3 days after stroke onset. The frequency of expectoration was variable with fluctuation, and half of the patients (47%) had to spit every 2–5 min during its climax. The duration of increased secretion ranged from 4 days to over 2 months. Half of the patients (53%) received anticholinergic treatment, and the response was fair to good. Conclusions: Our data provide clinical evidence that stroke patients with dorsal medulla involvement might present with bronchorrhea which seemed to be mediated via a parasympathetic mechanism. This is a treatable disease, and early diagnosis and treatment may greatly reduce patients’ suffering, avoid antibiotics abuse, reduce the incidence of aspiration pneumonia, and shorten the length of hospitalization.

Emotion Regulation via the Autonomic Nervous System in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

Despite growing interest in conceptualizing ADHD as involving disrupted emotion regulation, few studies have examined the physiological mechanisms related to emotion regulation in children with this disorder. This study examined parasympathetic and sympathetic nervous system reactivity via measures of respiratory sinus arrhythmia (RSA) and cardiac pre-ejection period (PEP) in children with ADHD (n=32) and typically developing controls (n=34), using a novel emotion task with four conditions: negative induction, negative suppression, positive induction, and positive suppression of affect. Both groups showed strong task-response effects in RSA. However, typically developing children showed systematic variation in parasympathetic activity (RSA) depending on both emotion valence (more activation for negative emotion, reduced activation for positive emotion) and task demand (more activation for suppression than induction). In contrast, children with ADHD displayed a stable pattern of elevated parasympathetic activity (RSA) across all task conditions compared to baseline. No group differences in sympathetic activity (PEP) were observed. It is concluded ADHD in childhood is associated with abnormal parasympathetic mechanisms involved in emotion regulation.

Modulation of amoebic hepatic abscess by the parasympathetic system

The neuro-immune network, in which the vagus nerve is involved, provides feedback between its afferent branches for signalling central nervous system from sites of injury through cytokines and its efferent branches, which release acetylcholine, an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic mechanisms participating in the inflammatory response in the liver, we studied the effects of a vagotomy on the innate immune response in hamsters with amoebic liver abscess. At 7 days post-infection, compared to the control, liver parasympathectomy resulted in a larger abscess size, a greater production of collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN-γ and increased numbers of IL-10 and IFN-γ-positive cells in situ, with no change in the number of macrophages and NK cells. Data indicate that the vagotomy disrupted the inflammatory response, causing an increase in the response against infection, then could favour the innervation of the liver by the sympathetic nervous system and would then take the control of the immune response by stimulating the conversion of macrophages to epithelioid cells; and through increased IL-10 production would induce the hepatic stellar cells to become myofibroblast collagen producer cells, thus forming a barrier of collagen and blocking trophozoite migration.

Mechanisms of reflex bladder activation by pudendal afferents

Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a β-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by -25% to -39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder contractions following administration of hexamethonium bromide confirmed that contractions were generated by pelvic efferent activation via the pelvic ganglion. These findings indicate that pudendal afferent stimulation evokes bladder contractions through convergence with pelvic afferents to increase pelvic efferent activity.