scholarly journals Functional and molecular plasticity of γ and α1 GABAA receptor subunits in the dorsal motor nucleus of the vagus after experimentally induced diabetes

2017 ◽  
Vol 118 (5) ◽  
pp. 2833-2841 ◽  
Author(s):  
Carie R. Boychuk ◽  
Katalin C. Smith ◽  
Bret N. Smith
Keyword(s):  
Motor Neurons ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Chronic Hyperglycemia ◽  
Γ Subunit ◽  
Dorsal Motor Nucleus ◽  
Electrophysiological Recordings ◽  
Increased Sensitivity ◽  
Experimentally Induced

Chronic experimentally induced hyperglycemia augments subunit-specific γ-aminobutyric acid A (GABAA) receptor-mediated inhibition of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV). However, the contribution of α1 or γ GABAA receptor subunits, which are ubiquitously expressed on central nervous system neurons, to this elevation in inhibitory tone have not been determined. This study investigated the effect of chronic hyperglycemia/hypoinsulinemia on α1- and γ-subunit-specific GABAA receptor-mediated inhibition using electrophysiological recordings in vitro and quantitative RT-PCR. DMV neurons from streptozotocin-treated mice demonstrated enhancement of both phasic and tonic inhibitory currents in response to application of the α1-subunit-selective GABAA receptor-positive allosteric modulator zolpidem. Responses to low concentrations of the GABAA receptor antagonist gabazine suggested an additional increased contribution of γ-subunit-containing receptors to tonic currents in DMV neurons. Consistent with the functional elevation in α1- and γ-subunit-dependent activity, transcription of both the α1- and γ2-subunits was increased in the dorsal vagal complex of streptozotocin-treated mice. Overall, these findings suggest an increased sensitivity to both zolpidem and gabazine after several days of hyperglycemia/hypoinsulinemia, which could contribute to altered parasympathetic output from DMV neurons in diabetes. NEW & NOTEWORTHY Glutamate and GABA signaling in the dorsal vagal complex is elevated after several days of chronic hyperglycemia in a mouse model of type 1 diabetes. We report persistently enhanced GABAA receptor-mediated responses to the somnolescent zolpidem in preganglionic vagal motor neurons. These results imply a broader impact of chronic hyperglycemia on central vagal function than previously appreciated and reinforce the hypothesis that diabetes effects in the brain can impact regulation of metabolic homeostasis.

scholarly journals Glutamatergic drive facilitates synaptic inhibition of dorsal vagal motor neurons after experimentally induced diabetes in mice

2016 ◽  
Vol 116 (3) ◽  
pp. 1498-1506 ◽  
Author(s):  
Carie R. Boychuk ◽  
Bret N. Smith
Keyword(s):  
Motor Neurons ◽  
Energy Homeostasis ◽  
Region Of Interest ◽  
Motor Nucleus ◽  
Gabaergic Neurotransmission ◽  
Amplitude Variability ◽  
Chronic Hyperglycemia ◽  
Electrophysiological Recordings

The role of central regulatory circuits in modulating diabetes-associated glucose dysregulation has only recently been under rigorous investigation. One brain region of interest is the dorsal motor nucleus of the vagus (DMV), which contains preganglionic parasympathetic motor neurons that regulate subdiaphragmatic visceral function. Previous research has demonstrated that glutamatergic and GABAergic neurotransmission are independently remodeled after chronic hyperglycemia/hypoinsulinemia. However, glutamatergic circuitry within the dorsal brain stem impinges on GABAergic regulation of the DMV. The present study investigated the role of glutamatergic neurotransmission in synaptic GABAergic control of DMV neurons after streptozotocin (STZ)-induced hyperglycemia/hypoinsulinemia by using electrophysiological recordings in vitro. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was elevated in DMV neurons from STZ-treated mice. The effect was abolished in the presence of the ionotropic glutamate receptor blocker kynurenic acid or the sodium channel blocker tetrodotoxin, suggesting that after STZ-induced hyperglycemia/hypoinsulinemia, increased glutamatergic receptor activity occurs at a soma-dendritic location on local GABA neurons projecting to the DMV. Although sIPSCs in DMV neurons normally demonstrated considerable amplitude variability, this variability was significantly increased after STZ-induced hyperglycemia/hypoinsulinemia. The elevated amplitude variability was not related to changes in quantal release, but rather correlated with significantly elevated frequency of sIPSCs in these mice. Taken together, these findings suggest that GABAergic regulation of central vagal circuitry responsible for the regulation of energy homeostasis undergoes complex functional reorganization after several days of hyperglycemia/hypoinsulinemia, including both glutamate-dependent and -independent forms of plasticity.

Galanin Inhibits Gut-Related Vagal Neurons in Rats

2004 ◽  
Vol 91 (5) ◽  
pp. 2330-2343 ◽  
Author(s):  
Zhenjun Tan ◽  
Ronald Fogel ◽  
Chunhui Jiang ◽  
Xueguo Zhang
Keyword(s):  
Potassium Channel ◽  
Reversal Potential ◽  
Outward Current ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Membrane Hyperpolarization ◽  
Dorsal Motor Nucleus

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.

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 The Neural Pathway of Reflex Regulation of Electroacupuncture at Orofacial Acupoints on Gastric Functions in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jianhua Liu ◽  
Wenbin Fu ◽  
Wei Yi ◽  
Zhenhua Xu ◽  
Nenggui Xu
Keyword(s):  
Myoelectric Activity ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Neural Pathway ◽  
Excitatory Effect ◽  
Reflex Regulation ◽  
Gastric Myoelectric Activity ◽  
Dorsal Motor Nucleus ◽  
Spike Bursts

Acupuncture has a reflex regulation in gastrointestinal functions, which is characterized with segment. In the present study, the neural pathway of electroacupuncture (EA) at orofacial acupoints (ST2) on gastric myoelectric activity (GMA) in rats was investigated. The results indicated that EA at ST2 facilitated spike bursts of GMA, which is similar to EA at limbs and opposite to EA at abdomen. The excitatory effect was abolished by the transaction of infraorbital nerves, dorsal vagal complex lesion, and vagotomy, respectively. In addition, microinjection of L-glutamate into the nucleus of the solitary tract (NTS) attenuated the excitatory effect. All these data suggest that the dorsal vagal complex is involved in the reflex regulation of EA at orofacial acupoints on gastric functions and NTS-dorsal motor nucleus of the vagus (DMV) inhibitory connections may be essential for it.

scholarly journals Optimized Protocol to Generate Spinal Motor Neuron Cells from Induced Pluripotent Stem Cells from Charcot Marie Tooth Patients

2020 ◽  
Vol 10 (7) ◽  
pp. 407
Author(s):  
Pierre-Antoine Faye ◽  
Nicolas Vedrenne ◽  
Federica Miressi ◽  
Marion Rassat ◽  
Sergii Romanenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Spinal Motor ◽  
Electrophysiological Recordings ◽  
Induced Pluripotent

Modelling rare neurogenetic diseases to develop new therapeutic strategies is highly challenging. The use of human-induced pluripotent stem cells (hiPSCs) is a powerful approach to obtain specialized cells from patients. For hereditary peripheral neuropathies, such as Charcot–Marie–Tooth disease (CMT) Type II, spinal motor neurons (MNs) are impaired but are very difficult to study. Although several protocols are available to differentiate hiPSCs into neurons, their efficiency is still poor for CMT patients. Thus, our goal was to develop a robust, easy, and reproducible protocol to obtain MNs from CMT patient hiPSCs. The presented protocol generates MNs within 20 days, with a success rate of 80%, using specifically chosen molecules, such as Sonic Hedgehog or retinoic acid. The timing and concentrations of the factors used to induce differentiation are crucial and are given hereby. We then assessed the MNs by optic microscopy, immunocytochemistry (Islet1/2, HB9, Tuj1, and PGP9.5), and electrophysiological recordings. This method of generating MNs from CMT patients in vitro shows promise for the further development of assays to understand the pathological mechanisms of CMT and for drug screening.

Nitric oxide-mediated excitatory effect on neurons of dorsal motor nucleus of vagus

1994 ◽  
Vol 266 (1) ◽  
pp. G154-G160 ◽  
Author(s):  
R. A. Travagli ◽  
R. A. Gillis
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Spontaneous Discharge ◽  
Motor Nucleus ◽  
Excitatory Effect ◽  
Dorsal Motor Nucleus ◽  
Ly 83583 ◽  
Spontaneous Firing Rate

The purpose of our study was to explore whether nitric oxide was involved as an intercellular messenger in the dorsal motor nucleus of the vagus (DMV). To achieve this purpose we examined DMV motoneurons of the rat in vitro with the use of the extracellular cell-attached recording technique. The motoneurons, in general, exhibit a spontaneous discharge and when exposed to NO-producing drugs (i.e., 3-300 microM L-arginine and 10-100 microM S-nitroso-N-acetylpenicillamine) exhibit a concentration-related increase in their spontaneous firing rate. Because NO activates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP), we tested dibutyryl-cGMP (30-300 microM) and found that it also excites DMV neurons. Perfusion of the DMV neurons with N omega-nitro-L-arginine (300 microM), an inhibitor of NO synthase (NOS), and with NO scavenger, reduced hemoglobin (1 microM), counteracted the excitatory effect of L-arginine and N-methyl-D-aspartate (NMDA). Perfusion of the preparation with LY-83583 (10 microM), an inhibitor of guanylate cyclase, also counteracted the effects of L-arginine and NMDA. These data indicate that NOS is present in DMV neurons, and that the excitatory effect of NMDA on these neurons is due in part to formation of NO and the resulting accumulation of cGMP in DMV neurons.

Inhibitory effect of somatostatin on vagal motoneurons in the rat brain stem in vitro

1989 ◽  
Vol 256 (1) ◽  
pp. C155-C159 ◽  
Author(s):  
J. Nabekura ◽  
Y. Mizuno ◽  
Y. Oomura
Keyword(s):  
Brain Stem ◽  
Rat Brain ◽  
Reversal Potential ◽  
Input Resistance ◽  
Inhibitory Effect ◽  
Hill Coefficient ◽  
Resting Membrane Potential ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus

Effects of somatostatin-14 (SRIF) on membrane electrical properties were studied in rat brain stem slice preparations maintained in vitro. SRIF hyperpolarized the resting membrane potential and decreased the input resistance of more than two-thirds of the 85 vagal motoneurons tested in the dorsal motor nucleus of the vagus. These effects persisted under synaptic blockade caused by perfusion with a solution containing tetrodotoxin or a Ca2+-free/high-Mg2+ solution and were dependent on the extracellular SRIF concentration (5 X 10(-8) to 1 X 10(-8) M). The Hill coefficient was estimated to be 2. The reversal potential of SRIF-induced hyperpolarization was affected by changing external K+ concentration. The results suggest that, in addition to its well-known peripheral action, SRIF may inhibit secretomotor functions of visceral organs by reducing vagal output in the central nervous system.

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