scholarly journals Insulin reduces excitation in gastric-related neurons of the dorsal motor nucleus of the vagus

2012 ◽  
Vol 303 (8) ◽  
pp. R807-R814 ◽  
Author(s):  
Camille B. Blake ◽  
Bret N. Smith
Keyword(s):  
Brain Stem ◽  
Synaptic Input ◽  
Energy Homeostasis ◽  
Gastric Wall ◽  
Insulin Receptors ◽  
Excitatory Input ◽  
Motor Nucleus ◽  
Action Potential Firing ◽  
Dorsal Motor Nucleus ◽  
The Brain

The dorsal motor nucleus of the vagus (DMV) in the caudal brain stem is composed mainly of preganglionic parasympathetic neurons that control the subdiaphragmatic viscera and thus participates in energy homeostasis regulation. Metabolic pathologies, including diabetes, can disrupt vagal circuitry and lead to gastric dysfunction. Insulin receptors (IRs) are expressed in the DMV, and insulin crosses the blood-brain barrier and is transported into the brain stem. Despite growing evidence that insulin action in the brain is critical for energy homeostasis, little is known about insulin's action in the DMV. We used whole cell patch-clamp recordings in brain stem slices to identify effects of insulin on membrane and synaptic input properties of DMV neurons, including a subset of gastric-related cells identified subsequent to injection of a retrograde label into the gastric wall. Insulin application significantly reduced the frequency of spontaneous and miniature excitatory, but not inhibitory postsynaptic currents, with no change in amplitude ( P < 0.05). Insulin also directly hyperpolarized the membrane potential (−4.2 ± 1.3 mV; P < 0.05) and reduced action potential firing ( P < 0.05). Insulin effects were eliminated in the presence of a ATP-dependent K+ (KATP) channel antagonist tolbutamide (200 μM), or the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (100 nM), suggesting that insulin inhibition of excitatory input to gastric-related DMV neurons was mediated by KATP channels and depended on PI3K activity. Insulin regulation of synaptic input in the DMV may influence autonomic visceral regulation and thus systemic glucose metabolism.

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

2017 ◽  
Vol 313 (5) ◽  
pp. G434-G441 ◽  
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.

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

2003 ◽  
Vol 285 (3) ◽  
pp. G566-G576 ◽  
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.

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

2004 ◽  
Vol 286 (4) ◽  
pp. R625-R633 ◽  
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.

Glutamate activation of neurons in CV-reactive areas of cat brain stem affects urinary bladder motility

1993 ◽  
Vol 265 (4) ◽  
pp. F520-F529 ◽  
Author(s):  
S. Y. Chen ◽  
S. D. Wang ◽  
C. L. Cheng ◽  
J. S. Kuo ◽  
W. C. De Groat ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Brain Stem ◽  
Locus Ceruleus ◽  
Ventrolateral Medulla ◽  
Reticular Nucleus ◽  
Motor Nucleus ◽  
Arterial Blood ◽  
Dorsal Motor Nucleus ◽  
The Brain ◽  
Stimulation Of

To investigate the interaction between cardiovascular (CV)-reactive areas in the brain stem and urinary bladder (UB) motility, 48 adult cats of either sex were anesthetized intraperitoneally with alpha-chloralose (40 mg/kg) and urethan (400 mg/kg). The changes of UB motility and systemic arterial blood pressure (SAP) were produced by microinjection of sodium glutamate (0.5 M, 100-200 nl) into the pressor, depressor, or vagobradycardiac areas of the brain stem. Stimulation of these CV-reactive areas increased or decreased UB motility. Areas that produced an increase in UB motility listed in decreasing order of effectiveness are locus ceruleus-parabrachial nucleus in the pons, dorsal medulla, dorsal motor nucleus of vagus, and ventrolateral medulla. Areas eliciting a decrease in UB motility listed in decreasing order are gigantocellular tegmental field, parvocellular reticular nucleus, and ambiguus nucleus. Stimulation of other pressor sites in medulla also increased UB motility. Activation of the paramedian reticular nucleus, which consistently produced depressor responses, and activation of raphe nuclei, which produced depressor or pressor responses, consistently decreased UB motility. The integrity of the vagus nerve was not essential for the UB response to brain stimulation. These findings indicate that neuronal mechanisms for controlling UB and CV functions coexist at many sites in the brain stem. At those sites that commonly produce changes in UB motility, the type of UB response (excitation or inhibition) was in the same direction as the change of SAP. However, at some sites responses were inverse. It is not known whether the responses of the UB and CV system are controlled by common or separate populations of neurons at these sites.

Neurons in the dorsal motor nucleus of the vagus may integrate vagal and spinal information from the GI tract

1995 ◽  
Vol 268 (5) ◽  
pp. G780-G790 ◽  
Author(s):  
W. E. Renehan ◽  
X. Zhang ◽  
W. H. Beierwaltes ◽  
R. Fogel
Keyword(s):  
Brain Stem ◽  
Vagal Afferents ◽  
High Threshold ◽  
Motor Nucleus ◽  
Potential Contribution ◽  
Gi Tract ◽  
Dorsal Motor Nucleus ◽  
Efferent Neurons ◽  
Spinal Afferents ◽  
The Brain

Previous investigations have provided evidence that the activity of parasympathetic efferent neurons in the dorsal motor nucleus of the vagus (DMNV) may be influenced by either vagal afferent or spinal input from the gastrointestinal (GI) tract. Many questions remain, however, regarding the nature of this input and its integration by the brain stem. The present study was designed to examine one important aspect of this issue: the potential contribution of the spinal input to the brain stem in the generation of the response properties of intestine-sensitive neurons in the DMNV. Using intracellular recording and labeling techniques in adult rats, we found that ascending spinal pathways were capable of conveying both low- and high-threshold visceral information to the DMNV. We also determined that the neurons in the nucleus of the solitary tract failed to respond to intestinal distention when the vagal afferents to the brain stem had been severed, suggesting that the spinal projections terminate directly on the DMNV neurons. These data lend support to the emerging hypothesis that the spinal afferents that accompany the abdominal splanchnics are capable of responding to both innocuous and noxious stimuli. The results also suggest that the neurons in the DMNV play a larger role in the integration of visceral sensory information than was previously realized.

scholarly journals Differential organization of excitatory and inhibitory synapses within the rat dorsal vagal complex

2011 ◽  
Vol 300 (1) ◽  
pp. G21-G32 ◽  
Author(s):  
Tanja Babic ◽  
Kirsteen N. Browning ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Pancreatic Secretion ◽  
Firing Frequency ◽  
Inhibitory Synapses ◽  
Motor Nucleus ◽  
Glutamatergic Synapses ◽  
Dorsal Motor Nucleus ◽  
Whole Cell Patch Clamp ◽  
The Brain ◽  
Upper Gastrointestinal

The dorsal motor nucleus of the vagus (DMV) is pivotal in the regulation of upper gastrointestinal functions, including motility and both gastric and pancreatic secretion. DMV neurons receive robust GABA- and glutamatergic inputs. Microinjection of the GABAA antagonist bicuculline (BIC) into the DMV increases pancreatic secretion and gastric motility, whereas the glutamatergic antagonist kynurenic acid (KYN) is ineffective unless preceded by microinjection of BIC. We used whole cell patch-clamp recordings with the aim of unveiling the brain stem neurocircuitry that uses tonic GABA- and glutamatergic synapses to control the activity of DMV neurons in a brain stem slice preparation. Perfusion with BIC altered the firing frequency of 71% of DMV neurons, increasing firing frequency in 80% of the responsive neurons and decreasing firing frequency in 20%. Addition of KYN to the perfusate either decreased (52%) or increased (25%) the firing frequency of BIC-sensitive neurons. When KYN was applied first, the firing rate was decreased in 43% and increased in 21% of the neurons; further perfusion with BIC had no additional effect in the majority of neurons. Our results indicate that there are several permutations in the arrangements of GABA- and glutamatergic inputs controlling the activity of DMV neurons. Our data support the concept of brain stem neuronal circuitry that may be wired in a finely tuned organ- or function-specific manner that permits precise and discrete modulation of the vagal motor output to the gastrointestinal tract.

Glutamatergic plasticity within neurocircuits of the dorsal vagal complex and the regulation of gastric functions

2021 ◽  
Author(s):  
Courtney Clyburn ◽  
Kirsteen N Browning
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Intestinal Secretion ◽  
Motor Nucleus ◽  
Glutamatergic Transmission ◽  
Gi Tract ◽  
Dorsal Motor Nucleus ◽  
Efferent Neurons ◽  
Rapid Transmission

The meticulous regulation of the gastrointestinal (GI) tract is required for the co-ordination of gastric motility and emptying, intestinal secretion, absorption, and transit as well as for the overarching management of food intake and energy homeostasis. Disruption of GI functions is associated with the development of severe GI disorders as well as the alteration of food intake and caloric balance. Functional GI disorders as well as the dysregulation of energy balance and food intake are frequently associated with, or result from, alterations in the central regulation of GI control. The faithful and rapid transmission of information from the stomach and upper GI tract to second order neurons of the nucleus of the tractus solitarius (NTS) relies on the delicate modulation of excitatory glutamatergic transmission, as does the relay of integrated signals from the NTS to parasympathetic efferent neurons of the dorsal motor nucleus of the vagus (DMV). Many studies have focused on understanding the physiological and pathophysiological modulation of these glutamatergic synapses, although their role in the control and regulation of GI functions has lagged behind that of cardiovascular and respiratory functions. The purpose of this review is to examine the current literature exploring the role of glutamatergic transmission in the DVC in the regulation of Gl functions.

scholarly journals Postnatal developmental expressions of neurotransmitters and receptors in various brain stem nuclei of rats

2005 ◽  
Vol 98 (4) ◽  
pp. 1442-1457 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley
Keyword(s):  
Brain Stem ◽  
Respiratory Control ◽  
Nucleus Ambiguus ◽  
Hypoglossal Nucleus ◽  
Motor Nucleus ◽  
Developmental Trend ◽  
Receptor Subunit ◽  
Cuneate Nucleus ◽  
Glycine Receptors ◽  
Dorsal Motor Nucleus

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3–4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-d-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3–4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Bötzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.

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

2002 ◽  
Vol 282 (2) ◽  
pp. R537-R545 ◽  
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.

Postnatal changes in cytochrome oxidase expressions in brain stem nuclei of rats: implications for sensitive periods

2003 ◽  
Vol 95 (6) ◽  
pp. 2285-2291 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley
Keyword(s):  
Brain Stem ◽  
Cytochrome Oxidase ◽  
Vestibular Nucleus ◽  
Glycine Receptor ◽  
Nucleus Ambiguus ◽  
Medial Vestibular Nucleus ◽  
Hypoglossal Nucleus ◽  
Motor Nucleus ◽  
Sensitive Periods ◽  
The Brain

Previously, we reported that cytochrome oxidase (CO) activity in the rat pre-Bötzinger complex (PBC) exhibited a plateau on postnatal days (P) 3–4 and a prominent decrease on P12 (Liu and Wong-Riley, J Appl Physiol 92: 923–934, 2002). These changes were correlated with a concomitant reduction in the expression of glutamate and N-methyl-d-aspartate receptor subunit 1 and an increase in GABA, GABAB, glycine receptor, and glutamate receptor 2. To determine whether changes were limited to the PBC, the present study aimed at examining the expression of CO in a number of brain stem nuclei, with or without known respiratory functions from P0 to P21 in rats: the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, nucleus raphe obscurus, dorsal motor nucleus of the vagus nerve, medial accessory olivary nucleus, spinal nucleus of the trigeminal nerve, and medial vestibular nucleus (MVe). Results indicated that, in all of the brain stem nuclei examined, CO activity exhibited a general increase with age from P0 to P21, with MVe having the slowest rise. Notably, in all of the nuclei examined except for MVe, there was a plateau or decrease at P3–P4 and a prominent rise-fall-rise pattern at P11–P13, similar to that observed in the PBC. In addition, there was a fall-rise-fall pattern at P15–P17 in these nuclei, instead of a plateau pattern in the PBC. Our data suggest that the two postnatal periods with reduced CO activity, P3–P4 and especially P12, may represent common sensitive periods for most of the brain stem nuclei with known or suspected respiratory control functions.

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