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 Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 908
Author(s):  
Kirsteen N. Browning ◽  
Kaitlin E. Carson
Keyword(s):  
Food Intake ◽  
Vagus Nerve ◽  
Sensory Information ◽  
Specific Reference ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
The Central Nervous System ◽  
Complex Integration ◽  
The Many

The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake.

scholarly journals The Role of the Dorsal Vagal Complex and the Vagus Nerve in Feeding Effects of Melanocortin-3/4 Receptor Stimulation*

Endocrinology ◽  
2000 ◽  
Vol 141 (4) ◽  
pp. 1332-1337 ◽  
Author(s):  
Diana L. Williams ◽  
Joel M. Kaplan ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Vagus Nerve ◽  
Messenger Rna ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Ventricular Response ◽  
Feeding Effects ◽  
Diet Intake

Abstract Fourth intracerebroventricular (4th-icv) administration of the melanocortin-3/4 receptor (MC3/4-R) agonist, MTII, reduces food intake; the antagonist, SHU9119, increases feeding. The dorsal motor nucleus of the vagus nerve (DMX) contains the highest density of MC4-R messenger RNA in the brain. To explore the possibility that the DMX contributes to 4th-icv MC4-R effects, we delivered doses of MTII and SHU9119 that are subthreshold for ventricular response unilaterally through a cannula centered above the DMX. MTII markedly suppressed 2-h (50%), 4-h (50%), and 24-h (33%) intake. Feeding was significantly increased 4 h (50%) and 24 h (20%) after SHU9119 injections. These results suggest that receptors in the DMX, or the dorsal vagal complex more generally, underlie effects obtained with 4th-icv administration of these ligands. We investigated possible vagal mediation of 4th-icv MTII effects by giving the agonist to rats with subdiaphragmatic vagotomy. MTII suppressed 2-, 4-, and 24-h liquid diet intake (∼80%) to the same extent in vagotomized and surgical control rats. We conclude that stimulation or antagonism of MC3/4-Rs in the dorsal vagal complex yields effects on food intake that do not require an intact vagus nerve.

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 NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xinyan Gao ◽  
Yongfa Qiao ◽  
Baohui Jia ◽  
Xianghong Jing ◽  
Bin Cheng ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gastric Motility ◽  
Low Frequency ◽  
Synaptic Activity ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Vagal Reflex ◽  
Precise Molecular Mechanism ◽  
Lines Of Evidence

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

scholarly journals NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21)

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Xin Zhang ◽  
Bin Cheng ◽  
Xianghong Jing ◽  
Yongfa Qiao ◽  
Xinyan Gao ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Nmda Receptor ◽  
Ampa Receptor ◽  
Gastrointestinal Motility ◽  
Kynurenic Acid ◽  
Basic Mechanism ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Lines Of Evidence

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

scholarly journals Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

2016 ◽  
Vol 310 (2) ◽  
pp. E103-E115 ◽  
Author(s):  
Lionel Carneiro ◽  
Sarah Geller ◽  
Xavier Fioramonti ◽  
Audrey Hébert ◽  
Cendrine Repond ◽  
...  
Keyword(s):  
Food Intake ◽  
Ketone Body ◽  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Body Level ◽  
Homeostasis Regulation ◽  
The Impact ◽  
Body Concentration

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Prior vagotomy blocks VMH obesity in pair-fed rats

1981 ◽  
Vol 240 (5) ◽  
pp. E573-E583 ◽  
Author(s):  
J. E. Cox ◽  
T. L. Powley
Keyword(s):  
Food Intake ◽  
Cell Loss ◽  
Ventromedial Hypothalamus ◽  
Motor Nucleus ◽  
Previous Suggestion ◽  
Hypothalamic Obesity ◽  
Dorsal Motor Nucleus ◽  
Gastric Contents ◽  
Feeding Regimen ◽  
Protein Output

Previously vagotomized, ventromedial hypothalamus (VMH)-lesioned rats and sham-lesioned controls were maintained on an intragastric pair-feeding regimen in which nonvagotomized VMH rats deposit excessive fat. Hypothalamic lesions were produced after 6 days of adaptation to pair feeding, and the experiment continued for 30 days postlesion. Extent of vagotomy was determined with a multiple-regression procedure with cell loss in the dorsal motor nucleus of the vagus, fasting gastric contents, and basal pancreatic protein output as predictor variables. The correlation was 0.95 between this set of indexes and the adequacy of a vagotomy for preventing hypothalamic obesity. Thus, radical vagotomies precluded the typical accumulation of significantly increased levels of carcass fat in lesioned animals (16.3 vs. 14.0% for controls). VMH rats with less extensive transections accumulated substantially more fat (25.9%). This outcome suggests that vagotomy produces a specific blockade of lesion-produced disturbances in metabolism leading to obesity. It fails to support a previous suggestion that vagal section blocks VMH obesity merely as a nonspecific surgical restriction of food intake because vagotomy was effective even though its effects on food intake could not operate.

scholarly journals GABAA receptor currents in the dorsal motor nucleus of the vagus in females: influence of ovarian cycle and 5α-reductase inhibition

2019 ◽  
Vol 122 (5) ◽  
pp. 2130-2141
Author(s):  
Erica L. Littlejohn ◽  
Liliana Espinoza ◽  
Monica M. Lopez ◽  
Bret N. Smith ◽  
Carie R. Boychuk
Keyword(s):  
Sex Differences ◽  
Motor Neurons ◽  
Ovarian Cycle ◽  
Receptor Activity ◽  
Motor Nucleus ◽  
Gabaergic Neurotransmission ◽  
Physiological Processes ◽  
Dorsal Motor Nucleus

The dorsal motor nucleus of the vagus (DMV) contains the preganglionic motor neurons important in the regulation of glucose homeostasis and gastrointestinal function. Despite the role of sex in the regulation of these processes, few studies examine the role of sex and/or ovarian cycle in the regulation of synaptic neurotransmission to the DMV. Since GABAergic neurotransmission is critical to normal DMV function, the present study used in vitro whole cell patch-clamping to investigate whether sex differences exist in GABAergic neurotransmission to DMV neurons. It additionally investigated whether the ovarian cycle plays a role in those sex differences. The frequency of phasic GABAA receptor-mediated inhibitory postsynaptic currents in DMV neurons from females was lower compared with males, and this effect was TTX sensitive and abolished by ovariectomy (OVX). Amplitudes of GABAergic currents (both phasic and tonic) were not different. However, females demonstrated significantly more variability in the amplitude of both phasic and tonic GABAA receptor currents. This difference was eliminated by OVX in females, suggesting that these differences were related to reproductive hormone levels. This was confirmed for GABAergic tonic currents by comparing females in two ovarian stages, estrus versus diestrus. Female mice in diestrus had larger tonic current amplitudes compared with those in estrus, and this increase was abolished after administration of a 5α-reductase inhibitor but not modulation of estrogen. Taken together, these findings demonstrate that DMV neurons undergo GABAA receptor activity plasticity as a function of sex and/or sex steroids. NEW & NOTEWORTHY Results show that GABAergic signaling in dorsal vagal motor neurons (DMV) demonstrates sex differences and fluctuates across the ovarian cycle in females. These findings are the first to demonstrate that female GABAA receptor activity in this brain region is modulated by 5α-reductase-dependent hormones. Since DMV activity is critical to both glucose and gastrointestinal homeostasis, these results suggest that sex hormones, including those synthesized by 5α-reductase, contribute to visceral, autonomic function related to these physiological processes.

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

2003 ◽  
Vol 285 (2) ◽  
pp. R479-R489 ◽  
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.

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