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 ◽  
...  

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.

2002 ◽  
Vol 88 (1) ◽  
pp. 49-63 ◽  
Author(s):  
Xueguo Zhang ◽  
Ronald Fogel

Data have shown that the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) play important roles in the regulation of gastrointestinal function and eating behavior. Anatomical studies have demonstrated direct projections from the PVN to the DMNV and physiological studies showed that the DMNV mediates many of the effects of PVN stimulation and electrical current stimulation of the PVN excites a subset of DMNV neurons. The aim of this study was to characterize the role of glutamate receptors in the excitatory influence of the PVN on gut-related DMNV neurons. Using single-cell recording techniques, we determined the effects of kynurenic acid, 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), anddl-2-amino-5-phosphonopentanoic acid (dl-AP5) on the increase in firing rate due to electrical current stimulation of the PVN. In initial experiments, we studied 24 DMNV neurons excited by electrical current stimulation of the PVN. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, prevented the PVN effect in 22 neurons and significantly attenuated the effect in the other cells. Nine of these neurons demonstrated an inhibition in firing rate with PVN stimulation after pretreatment with kynurenic acid. In a separate group of 12 neurons, we determined the effects of CNQX (1.2 nmol) injected into the DMNV. This AMPA receptor antagonist completely blocked the excitatory response to PVN stimulation of six DMNV neurons and significantly attenuated the response of the other six DMNV neurons. The addition of 1.2 nmol dl-AP5, a N-methyl-d-aspartate (NMDA) receptor antagonist, further attenuated the response to PVN stimulation in four of the five DMNV neurons that were still excited after CNQX treatment. The fifth neuron demonstrated PVN- induced inhibition of firing rate after treatment with CNQX and dl-AP5. In a separate group of 11 DMNV neurons excited by electrical stimulation of the PVN,dl-AP5 partially attenuated the excitatory responses of only four DMNV neurons and did not block the excitation of any cells. The mean latency (14 neurons tested) from the PVN to the DMNV was 37.71 ± 2.40 (SE) ms. Monosynaptic action potentials and excitatory postsynaptic potentials were demonstrated in three DMNV neurons by intracellular recording. Our results indicate that glutamate released from PVN neurons projecting to the DMNV excite the gut-related vagal motor neurons by acting predominantly on the AMPA receptor. The NMDA receptor plays only a minor role in the excitatory effect.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xinyan Gao ◽  
Yongfa Qiao ◽  
Baohui Jia ◽  
Xianghong Jing ◽  
Bin Cheng ◽  
...  

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.


1996 ◽  
Vol 57 (1-2) ◽  
pp. 22-28 ◽  
Author(s):  
Shin-Hee Yoon ◽  
Sang-Soo Sim ◽  
Sang-June Hahn ◽  
Duck-Joo Rhie ◽  
Yang-Hyeok Jo ◽  
...  

Author(s):  
Courtney Clyburn ◽  
Kirsteen N Browning

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.


2019 ◽  
Vol 122 (5) ◽  
pp. 2130-2141
Author(s):  
Erica L. Littlejohn ◽  
Liliana Espinoza ◽  
Monica M. Lopez ◽  
Bret N. Smith ◽  
Carie R. Boychuk

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.


2015 ◽  
Author(s):  
Denis Zakharov ◽  
Lapis Christopher ◽  
Boris Gutkin ◽  
Alexey Kuznetsov

Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency.


2005 ◽  
Vol 1032 (1-2) ◽  
pp. 116-122 ◽  
Author(s):  
Chuan Yong Liu ◽  
Dong Ping Xie ◽  
Ke Jing Liu ◽  
Yu Qin Zhou ◽  
Jing Zhang Liu

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