Catecholaminergic neurons in rat dorsal motor nucleus of vagus project selectively to gastric corpus

Nitric oxide synthase-immunoreactive (NOS-IR) neurons in the rat caudal dorsal motor nucleus of the vagus (DMV) project selectively to the gastric fundus and may be involved in vagal reflexes controlling gastric distension. This study aimed to identify the gastric projections of tyrosine hydroxylase-immunoreactive (TH-IR) DMV neurons, whether such neurons colocalize NOS-IR, and if they are activated after esophageal distension. Gastric-projecting neurons were identified after injection of retrograde tracers into the muscle wall of the gastric fundus, corpus, or antrum/pylorus before removal and processing of the brain stems for TH- and NOS-IR. A significantly higher proportion of corpus- compared with fundus- and antrum/pylorus-projecting neurons were TH-IR (14% compared with 4% and 2%, respectively, P < 0.05). Colocalization of NOS- and TH-IR was never observed in gastric-projecting neurons. In rats tested for c-Fos activation after intermittent esophageal balloon distension, no colocalization with TH-IR was observed in DMV neurons. These findings suggest that TH-IR neurons in the caudal DMV project mainly to the gastric corpus, constitute a subpopulation distinct from that of nitrergic vagal neurons, and are not activated on esophageal distension.

Download Full-text

A reevaluation of the effects of stimulation of the dorsal motor nucleus of the vagus on gastric motility in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00863.2005 ◽

2007 ◽

Vol 292 (1) ◽

pp. R291-R307 ◽

Cited By ~ 34

Author(s):

Maureen T. Cruz ◽

Erin C. Murphy ◽

Niaz Sahibzada ◽

Joseph G. Verbalis ◽

Richard A. Gillis

Keyword(s):

Gastric Motility ◽

Intragastric Balloon ◽

Motor Nucleus ◽

Inhibitory Effects ◽

Inhibitory Pathways ◽

Dorsal Motor Nucleus ◽

Bilateral Vagotomy ◽

Oxide Synthase ◽

Intravenous Atropine ◽

Stimulation Of

Our primary purpose was to characterize vagal pathways controlling gastric motility by microinjecting l-glutamate into the dorsal motor nucleus of the vagus (DMV) in the rat. An intragastric balloon was used to monitor motility. In 39 out of 43 experiments, microinjection of l-glutamate into different areas of the DMV rostral to calamus scriptorius (CS) resulted in vagally mediated excitatory effects on motility. We observed little evidence for inhibitory effects, even with intravenous atropine or with activation of gastric muscle muscarinic receptors by intravenous bethanechol. Inhibition of nitric oxide synthase with Nω-nitro-l-arginine methyl ester (l-NAME) HCl did not augment DMV-evoked excitatory effects on gastric motility. Microinjection of l-glutamate into the DMV caudal to CS produced vagally mediated gastric inhibition that was resistant to l-NAME. l-Glutamate microinjected into the medial subnucleus of the tractus solitarius (mNTS) also produced vagally mediated inhibition of gastric motility. Motility responses evoked from the DMV were always blocked by ipsilateral vagotomy, while responses evoked from the mNTS required bilateral vagotomy to be blocked. Microinjection of oxytocin into the DMV inhibited gastric motility, but the effect was never blocked by ipsilateral vagotomy, suggesting that the effect may have been due to diffusion of oxytocin to the mNTS. Microinjection of substance P and N-methyl-d-aspartate into the DMV also produced inhibitory effects attributable to excitation of nearby mNTS neurons. Our results do not support previous studies indicating parallel vagal excitatory and inhibitory pathways originating in the DMV rostral to CS. Our results do support previous findings of vagal inhibitory pathways originating in the DMV caudal to CS.

Download Full-text

Baroreflex control of heart rate by oxytocin in the solitary-vagal complex

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00806.2000 ◽

2002 ◽

Vol 282 (2) ◽

pp. R537-R545 ◽

Cited By ~ 87

Author(s):

Keila T. Higa ◽

Eliana Mori ◽

Fabiano F. Viana ◽

Mariana Morris ◽

Lisete C. Michelini

Keyword(s):

Heart Rate ◽

Male Rats ◽

Motor Nucleus ◽

Baroreflex Control ◽

Dorsal Motor Nucleus ◽

Loading And Unloading ◽

Reflex Control ◽

Exercise Induced ◽

Baroreceptor Reflex Control ◽

The Brain

Previous work demonstrated that oxytocinergic projections to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia (2). In the present study, we tested the idea that oxytocin (OT) terminals in the solitary vagal complex [nucleus of the solitary tract (NTS)/dorsal motor nucleus of the vagus (DMV)] are involved in baroreceptor reflex control of heart rate (HR). Studies were conducted in male rats instrumented for chronic cardiovascular monitoring with a cannula in the NTS/DMV for brain injections. Basal mean arterial pressure and HR and reflex HR responses during loading and unloading of the baroreceptors (phenylephrine/sodium nitroprusside intravenously) were recorded after administration of a selective OT antagonist (OTant) or OT into the NTS/DMV. The NTS/DMV was selected for study because this region contains such a specific and dense concentration of OT-immunoreactive terminals. Vehicle injections served as a control. OT and OTant changed baroreflex control of HR in opposite directions. OT (20 pmol) increased the maximal bradycardic response (from −56 ± 9 to −75 ± 11 beats/min), whereas receptor blockade decreased the bradycardia (from −61 ± 13 to −35 ± 2 beats/min). OTant also reduced the operating range of the reflex, thus decreasing baroreflex gain (from −5.68 ± 1.62 to −2.83 ± 1.05 beats · min−1 · mmHg−1). OT injected into the NTS/DMV of atenolol-treated rats still potentiated the bradycardic responses to pressor challenges, whereas OT injections had no effect in atropine-treated rats. The brain stem effect was specific because neither vehicle administration nor injection of OT or OTant into the fourth cerebral ventricle had any effect. Our data suggest that OT terminals in the solitary vagal complex modulate reflex control of the heart, acting to facilitate vagal outflow and the slowdown of the heart.

Download Full-text

Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00155.2003 ◽

2003 ◽

Vol 285 (2) ◽

pp. R479-R489 ◽

Cited By ~ 68

Author(s):

R. C. Rogers ◽

R. A. Travagli ◽

G. E. Hermann

Keyword(s):

Large Population ◽

Central Nucleus ◽

Motor Nucleus ◽

Adrenoceptor Antagonist ◽

Dorsal Motor Nucleus ◽

Efferent Neurons ◽

Nos Inhibitor ◽

Immunohistochemical Techniques ◽

Oxide Synthase ◽

Local Brain

Activation of esophageal mechanosensors excites neurons in and near the central nucleus of the solitary tract (NSTc). In turn, NSTc neurons coordinate the relaxation of the stomach [i.e., the receptive relaxation reflex (RRR)] by modulating the output of vagal efferent neurons of the dorsal motor nucleus of the vagus (DMN). The NSTc area contains neurons with diverse neurochemical phenotypes, including a large population of catecholaminergic and nitrergic neurons. The aim of the present study was to determine whether either one of these prominent neuronal phenotypes was involved in the RRR. Immunohistochemical techniques revealed that repetitive esophageal distension caused 53% of tyrosine hydroxylase-immunoreactive (TH-ir) neurons to colocalize c-Fos in the NSTc. No nitric oxide synthase (NOS)-ir neurons in the NSTc colocalized c-Fos in either distension or control conditions. Local brain stem application (2 ng) of α-adrenoreceptor antagonists (i.e., α1-prazosin or α2-yohimbine) significantly reduced the magnitude of the esophageal distension-induced gastric relaxation to ∼55% of control conditions. The combination of yohimbine and prazosin reduced the magnitude of the reflex to ∼27% of control. In contrast, pretreatment with either the NOS-inhibitor NG-nitro-l-arginine methyl ester or the β-adrenoceptor antagonist propranolol did not interfere with esophageal distension-induced gastric relaxation. Unilateral microinjections of the agonist norepinephrine (0.3 ng) directed at the DMN were sufficient to mimic the transient esophageal-gastric reflex. Our data suggest that noradrenergic, but not nitrergic, neurons of the NSTc play a prominent role in the modulation of the RRR through action on α1- and α2-adrenoreceptors. The finding that esophageal afferent stimulation alone is not sufficient to activate NOS-positive neurons in the NSTc suggests that these neurons may be strongly gated by other central nervous system inputs, perhaps related to the coordination of swallowing or emesis with respiration.

Download Full-text

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00180.2017 ◽

2017 ◽

Vol 313 (5) ◽

pp. G434-G441 ◽

Cited By ~ 11

Author(s):

L. Anselmi ◽

L. Toti ◽

C. Bove ◽

R. A. Travagli

Keyword(s):

Receptor Antagonist ◽

Brain Stem ◽

Sch 23390 ◽

Systemic Administration ◽

Membrane Properties ◽

Receptor Subtype ◽

Motor Nucleus ◽

Gastric Tone ◽

Dorsal Motor Nucleus ◽

The Brain

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.

Download Full-text

Accumulation of Pathogenic Prion Protein (PrPSc) in Nervous and Lymphoid Tissues of Sheep with Subclinical Scrapie

Veterinary Pathology ◽

10.1354/vp.40-2-164 ◽

2003 ◽

Vol 40 (2) ◽

pp. 164-174 ◽

Cited By ~ 40

Author(s):

C. Ersdal ◽

M. J. Ulvund ◽

S. L. Benestad ◽

M. A. Tranulis

Keyword(s):

Lymph Node ◽

Prion Protein ◽

Spongiform Encephalopathy ◽

Lymphoid Tissues ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

The Central Nervous System ◽

Natural Scrapie ◽

First Time ◽

The Brain

All sheep older than 1 year of age from a flock of the Rygja breed in which clinical scrapie was detected for the first time in two animals (4%) were examined for accumulation of pathogenic prion protein (PrPSc) by immunohistochemistry in the obex, the cerebellum, and the medial retrophayngeal lymph node. In addition, six lambs, 2–3 months old, all offspring of PrPSc-positive dams, were examined for PrPSc in the ileal Peyers' patch (IPP), the distal jejunal lymph node, the spleen, and the medial retropharyngeal lymph node (RPLN). In this flock, 35% (17/48) of the adult sheep showed accumulation of PrPSc, an eightfold increase compared with clinical disease. All positives carried susceptible PrP genotypes. Three sheep had deposits of PrPSc in the RPLN and not in the brain, suggesting that this organ, easily accessible at slaughter, is suitable for screening purposes. Two 7-year-old clinically healthy homozygous V136Q171 ewes showed sparse immunostaining in the central nervous system and may have been infected as adults. Further, two littermates, 86-days-old, showed PrPSc in the IPP. Interestingly, one of these lambs had the intermediate susceptible PrP genotype, VA136QR171. In addition to early immunolabeling in the dorsal motor nucleus of the vagal nerve, a few of the sheep had early involvement of the cerebellum. In fact, a 2-year-old sheep had sparse deposits of PrPSc in the cerebellum only. Because experimental bovine spongiform encephalopathy (BSE) in sheep seems to behave in a similar manner as natural scrapie, these results, particularly regarding spread of infectivity, may have implications for the handling of BSE should it be diagnosed in sheep.

Download Full-text

Δ9-Tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00113.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. G566-G576 ◽

Cited By ~ 91

Author(s):

Marja D. Van Sickle ◽

Lorraine D. Oland ◽

Ken Mackie ◽

Joseph S. Davison ◽

Keith A. Sharkey

Keyword(s):

Receptor Antagonist ◽

Brain Stem ◽

Area Postrema ◽

Motor Nucleus ◽

Cb1 Receptors ◽

Dorsal Vagal Complex ◽

Dorsal Motor Nucleus ◽

Site Of Action ◽

Fos Expression ◽

The Brain

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

Download Full-text

Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.4.r1104 ◽

1999 ◽

Vol 277 (4) ◽

pp. R1104-R1111 ◽

Cited By ~ 11

Author(s):

Huiyuan Zheng ◽

Lisa Kelly ◽

Laurel M. Patterson ◽

Hans-Rudolf Berthoud

Keyword(s):

Nmda Receptor ◽

Area Postrema ◽

Additive Model ◽

Nmda Receptor Antagonist ◽

Gastric Distension ◽

Motor Nucleus ◽

Sucrose Intake ◽

Mk 801 ◽

Dorsal Motor Nucleus ◽

Fos Expression

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.

Download Full-text

Oral-pharyngeal-esophageal and gastric cues contribute to meal-induced c-fos expression

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.1.r223 ◽

1995 ◽

Vol 268 (1) ◽

pp. R223-R230 ◽

Cited By ~ 16

Author(s):

K. A. Fraser ◽

E. Raizada ◽

J. S. Davison

Keyword(s):

Area Postrema ◽

Receptor Activation ◽

Gastric Distension ◽

Motor Nucleus ◽

Gastric Fistula ◽

Gastric Balloon ◽

Sham Feeding ◽

Dorsal Motor Nucleus ◽

Caudal Level

We recently demonstrated that a meal induces c-fos immunoreactivity in the dorsal motor nucleus of the vagus (DMV), the nucleus of the tractus solitarius (NTS), and the area postrema (AP) of the rat brain stem. This response was not eliminated by the cholecystokinin A (CCK-A) antagonist L-364,718, a finding suggesting that feeding induces c-fos immunoreactivity by a pathway that is largely independent of CCK-A receptor activation. Consequently, the role of alternative gastrointestinal cues in the induction of c-fos was investigated. The induction of c-fos after oral-pharyngeal and esophageal stimuli was examined by use of a sham-feeding procedure via a gastric fistula. Gastric fistula-closed and fed rats displayed c-fos immunoreactivity similar to that of meal-fed rats seen previously. Fistula-open and fed rats showed the same degree of staining in the more rostral section of NTS examined as fistula-closed and fed rats, but fewer c-fos-positive nuclei in the more caudal level of the NTS. The potential for gastric distension to induce c-fos was assessed after the inflation of a gastric balloon. Physiological inflation of the balloon produced marked c-fos induction primarily in the medial NTS.

Download Full-text

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00143.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. R625-R633 ◽

Cited By ~ 51

Author(s):

Zixi (Jack) Cheng ◽

Hong Zhang ◽

Shang Z. Guo ◽

Robert Wurster ◽

David Gozal

Keyword(s):

Brain Stem ◽

Motor Neurons ◽

Nucleus Ambiguus ◽

Motor Nucleus ◽

Sprague Dawley ◽

Tracer Injection ◽

Cardiac Ganglia ◽

Dorsal Motor Nucleus ◽

Differential Control ◽

The Brain

In previous single-labeling experiments, we showed that neurons in the nucleus ambiguus (NA) and the dorsal motor 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 tracer injection sites in the brain stem using two different anterograde tracers {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.

Download Full-text