scholarly journals Sex differences in GABAergic neurotransmission to rat DMV neurons

2019 ◽  
Vol 317 (4) ◽  
pp. G476-G483 ◽  
Author(s):  
Yanyan Jiang ◽  
Tanja Babic ◽  
R. Alberto Travagli
Keyword(s):  
Gastric Motility ◽  
Functional Gastrointestinal Disorders ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Gastrointestinal Disorders ◽  
Motor Nucleus ◽  
Estrus Cycle ◽  
Gastric Tone ◽  
Gabaergic Neurotransmission ◽  
Dorsal Motor Nucleus

Functional gastrointestinal disorders, including delayed gastric emptying and decreased gastric motility, are more prevalent in women, suggesting a potential role for circulating gonadal hormones, including estrogen. Gastric motility is tuned by the vagal inputs arising from the dorsal motor nucleus of the vagus (DMV), which is itself controlled by tonic GABAergic inputs. Estrogen increases GABA functions in various central nervous system areas; however, the effect of the estrus cycle in modulating GABAergic inputs onto DMV neurons, hence vagal control of gastric motility, has not been investigated. The aim of the present study was to test the hypothesis that GABAergic tone to DMV neurons, hence the vagal output to the stomach, varies according to sex and the estrus cycle. Experiments were performed on age-matched Sprague-Dawley male and virgin female rats; females were subdivided according to the high-estrogen (HE) or low-estrogen (LE) period of their cycle. Whole-cell patch-clamp recordings were made from gastric-projecting DMV neurons, and the response to perfusion with the GABAA receptor antagonist bicuculline was examined. The response of corpus and antrum tone and motility to bicuculline microinjected in the dorsal vagal complex, recorded via strain gauges sewn to the anterior gastric surface, was also assessed. Bicuculline increased the firing rate of DMV neurons, as well as gastric tone and motility, to a larger extent in HE compared with LE or male rats, suggesting a higher GABAergic tone in HE female rats. Taken together, the data support the hypothesis that GABAergic tone to DMV neurons varies according to sex and estrus cycle. NEW & NOTEWORTHY GABAergic neurotransmission to the dorsal motor nucleus of the vagus (DMV) plays a pivotal role in the modulation of gastric tone and motility. Gastric motility is reduced in women and may contribute to the higher incidence of functional gastrointestinal disorders. In the present study, we report that GABAergic tone to rat DMV neurons, hence vagal output to the stomach, varies according to sex and estrus cycle, and the GABAergic tone is increased during the high-estrogen period of the estrus cycle.

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.

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

2007 ◽  
Vol 292 (1) ◽  
pp. R291-R307 ◽  
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.

scholarly journals Electroacupuncture Stimulation at CV12 Inhibits Gastric Motility via TRPV1 Receptor

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Zhi Yu ◽  
Xin Cao ◽  
Youbing Xia ◽  
Binbin Ren ◽  
Hong Feng ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Knockout Mice ◽  
Functional Gastrointestinal Disorders ◽  
Inhibitory Effect ◽  
Gastrointestinal Disorders ◽  
Dependent Manner ◽  
Wild Type ◽  
Trpv1 Receptor ◽  
Alternative Approaches ◽  
Trpv1 Antagonist

Gastric dysmotility is one of the major pathophysiological factors in functional gastrointestinal disorders. Acupuncture, as one of the alternative approaches, is efficacious in the treatment of gastrointestinal motility disorders; however, the mechanism underlying its action is unclear. In the present study, we used both capsazepine, a TRPV1 antagonist, and TRPV1 knockout mice. Animals were divided into wild-type group (WT), capsazepine injection group (CZP, 0.5 mg/kg, i.p.), and TRPV1 knockout mice group (TRPV1−/−). Each of these three groups was divided into three subgroups, which were subjected to EA stimulation at acupoint Zhongwan (CV12) at a different intensity (1, 2, or 4 mA). We demonstrated that electroacupuncture at Zhongwan (CV12) markedly inhibited gastric motility at 2 and 4 mA in an intensity-dependent manner in wild-type mice. The inhibitory effect was also observed in capsazepine-injected and TRPV1−/−mice but was no longer intensity dependent, indicating that TRPV1 is partially involved in the electroacupuncture-mediated modulation of gastric motility.

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 SUN-251 The Effects of Unilateral Vagotomy in Female Rats with Blockade of the Muscarinic System of the Suprachiasmatic Nucleus on Ovulation and Estradiol Serum Levels

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elizabeth Vieyra-Valdez ◽  
Julio Cesar Garcia-Tabla ◽  
Hugo Alberto Zarco-Juarez ◽  
Roberto Calderon-Ramos ◽  
Leticia Morales-Ledesma ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Suprachiasmatic Nucleus ◽  
Serum Levels ◽  
Female Rats ◽  
Motor Nucleus ◽  
Exact Probability ◽  
Dorsal Motor Nucleus ◽  
Endocrine Organs ◽  
The Right ◽  
Left Vagus

Abstract Several studies show that the suprachiasmatic nucleus (SCN) participates in the regulation of the functions of various endocrine organs through multisynaptic nerve pathways. Some of these pathways communicate the SCN with the dorsal motor nucleus of the vagus and the nucleus of the solitary tract, which are part of the origin of the vagus nerve (1). Previously we demonstrated that atropine (ATR) microinjection in the right SCN on the day of the proestrus, blocks ovulation, while the same treatment in the left SCN does it partially (2). In the present study we analyzed the possibility that the vagus nerve is one of the neural ways by which the SCN regulates the secretion of estradiol (E2) in the proestrus and subsequent ovulation. For this, cyclic rats were anesthetized with ketamine-xylazine at 09.00 of the day of the proestrus. The animals were randomly assigned to one of the following groups: rats with ATR (62.5 ng diluted in 0.3 µl of saline) microinjection in the right or left SCN, followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. The animals were sacrificed 5 h after surgery, and estradiol (E2) levels were measured. Other groups of animals with the same treatments were sacrificed 24 hours after surgery, and ovulation rate and number of ova shed were evaluated. The left vagus section did not modify the effects of ATR microinjection in the left SCN on ovulatory rate (2/5 vs. 4/7) and E2 secretion (46.6±9.0 vs. 51.3±9.0, pg/ml). In animals with ATR microinjection in the right SCN, the right vagus section increased the rate of ovulating animals (6/8 vs. 2/9, p <0.0001, Fisher’s exact probability test) and E2 levels (51.8±9.4 vs. 22.4 ± 4.0, p <0.05, two-way ANOVA, followed by Tukey’s multiple comparison test). Present results suggest that the right vagus nerve plays a role in the multisynaptic communication between the right SCN and the right ovary, while the left vagus does not. Reference: (1) Travagli, R. A. J. Physiol. 2007 Jul 15:582(Pt 2):471. (2) Vieyra et al., Reproductive Biology and Endocrinology. 2016 Jun 16 14(1):34, 1-11.Supported by CONACyT 236908; DGAPA-PAPIIT IN216519

Neurons in the vagal complex of the rat respond to mechanical and chemical stimulation of the GI tract

1998 ◽  
Vol 274 (2) ◽  
pp. G331-G341 ◽  
Author(s):  
Xueguo Zhang ◽  
William E. Renehan ◽  
Ronald Fogel
Keyword(s):  
Acid Secretion ◽  
Gastric Motility ◽  
Extracellular Recording ◽  
Chemical Stimulation ◽  
Inhibitory Neurons ◽  
Motor Nucleus ◽  
Acid Solutions ◽  
Gi Tract ◽  
Dorsal Motor Nucleus ◽  
Stimulation Of

Perfusing the duodenum with acid solutions dramatically reduces gastric motility and acid secretion. We propose that the presence of acid in the proximal small intestine initiates a vagovagal reflex that excites inhibitory neurons in the nucleus of the solitary tract (NST) and reduces the activity of the neurons in the dorsal motor nucleus of the vagus nerve (DMNV). However, results from several investigations suggest that the relevant circuit may not be as simple as we had believed. The present study was designed to address this dilemma by employing intracellular and extracellular recording and intracellular labeling techniques to provide direct information on the activity of neurons in the NST and DMNV during and after intestinal exposure to acid solutions. The results obtained prove that NST and DMNV neurons respond to HCl in the duodenum. In some instances, these neurons were very stimulus specific, although the majority of the cells in our sample (47% of NST neurons and 86% of DMNV neurons) also responded to distension of the stomach and/or duodenum. It is important to note, however, that many of the more broadly responsive neurons in the dorsal vagal complex were able to distinguish between mechanical and chemical stimulation of the gastrointestinal (GI) tract. Most of the NST neurons that responded to duodenal perfusion with HCl were excited by this stimulus. Conversely, activity of most of the DMNV neurons decreased after the onset of the HCl stimulus. These findings verify the existence of a vagovagal reflex pathway initiated by duodenal perfusion with acid. Presumably, this reflex would decrease gastric motility and acid secretion, reducing the amount of acid that enters the duodenum and ultimately protecting the intestinal mucosa.

Glucose acts in the CNS to regulate gastric motility during hypoglycemia

2003 ◽  
Vol 285 (5) ◽  
pp. R1192-R1202 ◽  
Author(s):  
Min Shi ◽  
Allison R. Jones ◽  
Mark S. Niedringhaus ◽  
Rebecca J. Pearson ◽  
Ann M. Biehl ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Glucose ◽  
Motor Function ◽  
Gastric Motility ◽  
Motor Nucleus ◽  
Gastric Tone ◽  
Antral Motility ◽  
Gastric Motor Function ◽  
Gastric Contractions

Our purposes were to 1) develop an animal model where intravenously (iv) administered d-glucose consistently inhibited antral motility, and 2) use this model to assess whether iv glucose acts to inhibit motility from a peripheral or a central nervous system site and to elucidate the factor(s) that determine(s) whether stomach motor function is sensitive to changes in blood glucose. Rats were anesthetized with α-chloralose-urethane, and antral motility was measured by a strain-gauge force transducer sutured to the antrum. In some cases, antral motility and gastric tone were measured by monitoring intragastric balloon pressure. Increases in blood glucose were produced by continuous iv infusion of 25% d-glucose at 2 ml/h. Inhibition of antral motility and gastric tone was observed when gastric contractions were induced by hypoglycemia (subcutaneously administered insulin, 2.5 IU/animal). In contrast, no inhibition of gastric motor function was observed when glucose infusion was tested on gastric contractions that were 1) spontaneously occurring, 2) evoked by iv administered bethanechol in vagotomized animals, and 3) evoked by the TRH analog RX77368, microinjected into the dorsal motor nucleus of the vagus. Using the model of insulin-induced hypoglycemia to increase gastric motor activity, we found that neither sectioning the hepatic branch of the vagus ( n = 5), nor treating animals with capsaicin to destroy sensory vagal afferent nerves ( n = 5) affected the ability of iv d-glucose to inhibit gastric motor function. Our results indicate that an important factor determining whether stomach motor function will be sensitive to changes in blood glucose is the method used to stimulate gastric contractions, and that the primary site of the inhibitory action of iv glucose on gastric motility is the central nervous system rather than the periphery.

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.

scholarly journals GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

2009 ◽  
Vol 296 (1) ◽  
pp. G101-G111 ◽  
Author(s):  
Melissa A. Herman ◽  
Maureen T. Cruz ◽  
Niaz Sahibzada ◽  
Joseph Verbalis ◽  
Richard A. Gillis
Keyword(s):  
Gastric Motility ◽  
Kynurenic Acid ◽  
Nucleus Tractus Solitarius ◽  
Afferent Nerve ◽  
Projection Neurons ◽  
Motor Nucleus ◽  
Nerve Terminals ◽  
Receptor Blockade ◽  
Dorsal Motor Nucleus ◽  
Vagal Afferent

It has been proposed that there is an “apparent monosynaptic” connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes ( 6 ). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release l-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABAA receptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (−1.6 ± 0.2 mmHg, P < 0.05, n = 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABAA receptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or NG-nitro-l-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABAA receptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABAA receptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit.

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