scholarly journals Acute high-fat diet upregulates glutamatergic signaling in the dorsal motor nucleus of the vagus

2018 ◽  
Vol 314 (5) ◽  
pp. G623-G634 ◽  
Author(s):  
Courtney Clyburn ◽  
R. Alberto Travagli ◽  
Kirsteen N. Browning
Keyword(s):  
Nmda Receptor ◽  
High Fat Diet ◽  
Nmda Receptor Antagonist ◽  
Motor Nucleus ◽  
High Fat ◽  
Action Potential Firing ◽  
Initial Exposure ◽  
Dorsal Motor Nucleus ◽  
Glutamatergic Signaling ◽  
Potential Firing

Obesity is associated with dysregulation of vagal neurocircuits controlling gastric functions, including food intake and energy balance. In the short term, however, caloric intake is regulated homeostatically although the precise mechanisms responsible are unknown. The present study examined the effects of acute high-fat diet (HFD) on glutamatergic neurotransmission within central vagal neurocircuits and its effects on gastric motility. Sprague-Dawley rats were fed a control or HFD diet (14% or 60% kcal from fat, respectively) for 3–5 days. Whole cell patch-clamp recordings and brainstem application of antagonists were used to assess the effects of acute HFD on glutamatergic transmission to dorsal motor nucleus of the vagus (DMV) neurons and subsequent alterations in gastric tone and motility. After becoming hyperphagic initially, caloric balance was restored after 3 days following HFD exposure. In control rats, the non- N-methyl-d-aspartate (NMDA) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), but not the NMDA receptor antagonist, amino-5-phosphonopentanoate (AP5), significantly decreased excitatory synaptic currents and action potential firing rate in gastric-projecting DMV neurons. In contrast, both AP5 and DNQX decreased excitatory synaptic transmission and action potential firing in acute HFD neurons. When microinjected into the brainstem, AP5, but not DNQX, decreased gastric motility and tone in acute HFD rats only. These results suggest that acute HFD upregulates NMDA receptor-mediated currents, increasing DMV neuronal excitability and activating the vagal efferent cholinergic pathway, thus increasing gastric tone and motility. Although such neuroplasticity may be a persistent adaptation to the initial exposure to HFD, it may also be an important mechanism in homeostatic regulation of energy balance. NEW & NOTEWORTHY Vagal neurocircuits are critical to the regulation of gastric functions, including satiation and food intake. Acute high-fat diet upregulates glutamatergic signaling within central vagal neurocircuits via activation of N-methyl-d-aspartate receptors, increasing vagal efferent drive to the stomach. Although it is possible that such neuroplasticity is a persistent adaptation to initial exposure to the high-fat diet, it may also play a role in the homeostatic control of feeding.

Effects of 5-HT alone and its interaction with TRH on neurons in rat dorsal motor nucleus of the vagus

1995 ◽  
Vol 268 (2) ◽  
pp. G292-G299 ◽  
Author(s):  
R. A. Travagli ◽  
R. A. Gillis
Keyword(s):  
Firing Rate ◽  
Animal Studies ◽  
Motor Nucleus ◽  
Excitatory Effect ◽  
Action Potential Firing ◽  
Patch Clamp Technique ◽  
Dorsal Motor Nucleus ◽  
Potential Firing ◽  
Cell Current

The purpose of this study was to determine whether exposure to thyrotropin-releasing hormone (TRH) enhances the excitatory effect of 5-hydroxytryptamine (5-HT) on motoneurons of the dorsal motor nucleus of the vagus (DMV) as described in whole animal studies. For this purpose we used the patch-clamp technique applied to rat brain stem slices. Exposure of DMV motoneurons to concentrations of 5-HT (0.1-3 microM) resulted in a concentration-related increase in spontaneous firing rate. As previously described by Travagli et al. [Am. J. Physiol. 263 (Gastrointest. Liver Physiol. 26): G508-G517, 1992], TRH (1-30 microM) increased action potential firing rate. Indeed, when TRH perfusion increased the firing rate, addition of 5-HT to the perfusing solution exerted no further excitation of the DMV motoneuron, indicating that there was no summation of response. Studies using whole cell current recordings showed a common action of 5-HT and TRH in antagonizing the Ca(2+)-dependent afterhyperpolarizing current (IAHP). Again, interaction studies between TRH and 5-HT indicated no enhancing effect of TRH on 5-HT-induced antagonism of IAHP. In conclusion, our data indicated that the enhancement of 5-HT-induced excitation of DMV motoneurons by TRH described by in vivo rat experiments is not due to an interaction of TRH and 5-HT directly on the DMV motoneuron.

scholarly journals Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals

1999 ◽  
Vol 277 (4) ◽  
pp. R1104-R1111 ◽  
Author(s):  
Huiyuan Zheng ◽  
Lisa Kelly ◽  
Laurel M. Patterson ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Nmda Receptor ◽  
Area Postrema ◽  
Additive Model ◽  
Nmda Receptor Antagonist ◽  
Gastric Distension ◽  
Motor Nucleus ◽  
Sucrose Intake ◽  
Mk 801 ◽  
Dorsal Motor Nucleus ◽  
Fos Expression

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.

scholarly journals High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon

2016 ◽  
Vol 311 (2) ◽  
pp. G210-G220 ◽  
Author(s):  
Yogesh Bhattarai ◽  
David Fried ◽  
Brian Gulbransen ◽  
Mark Kadrofske ◽  
Roxanne Fernandes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
High Fat Diet ◽  
Neuromuscular Transmission ◽  
Bk Channel ◽  
High Fat ◽  
Action Potential Firing ◽  
Potential Firing

We tested the hypothesis that colonic enteric neurotransmission and smooth muscle cell (SMC) function are altered in mice fed a high-fat diet (HFD). We used wild-type (WT) mice and mice lacking the β1-subunit of the BK channel (BKβ1−/−). WT mice fed a HFD had increased myenteric plexus oxidative stress, a 28% decrease in nitrergic neurons, and a 20% decrease in basal nitric oxide (NO) levels. Circular muscle inhibitory junction potentials (IJPs) were reduced in HFD WT mice. The NO synthase inhibitor nitro-l-arginine (NLA) was less effective at inhibiting relaxations in HFD compared with control diet (CD) WT mice (11 vs. 37%, P < 0.05). SMCs from HFD WT mice had depolarized membrane potentials (−47 ± 2 mV) and continuous action potential firing compared with CD WT mice (−53 ± 2 mV, P < 0.05), which showed rhythmic firing. SMCs from HFD or CD fed BKβ1−/− mice fired action potentials continuously. NLA depolarized membrane potential and caused continuous firing only in SMCs from CD WT mice. Sodium nitroprusside (NO donor) hyperpolarized membrane potential and changed continuous to rhythmic action potential firing in SMCs from HFD WT and BKβ1−/− mice. Migrating motor complexes were disrupted in colons from BKβ1−/− mice and HFD WT mice. BK channel α-subunit protein and β1-subunit mRNA expression were similar in CD and HFD WT mice. We conclude that HFD-induced obesity disrupts inhibitory neuromuscular transmission, SMC excitability, and colonic motility by promoting oxidative stress, loss of nitrergic neurons, and SMC BK channel dysfunction.

scholarly journals GABAB Receptor Activation Promotes Seizure Activity in the Juvenile Rat Hippocampus

1999 ◽  
Vol 82 (2) ◽  
pp. 638-647 ◽  
Author(s):  
Rita Motalli ◽  
Jacques Louvel ◽  
Virginia Tancredi ◽  
Irène Kurcewicz ◽  
Doreen Wan-Chow-Wah ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Ictal Activity ◽  
Dentate Hilus

We analyzed how the GABAB receptor agonist baclofen (10–50 μM) influences the activity induced by 4-aminopyridine (4-AP, 50 μM) in the CA3 area of hippocampal slices obtained from 12- to 25-day-old rats. Interictal and ictal discharges along with synchronous GABA-mediated potentials occurred spontaneously in the presence of 4-AP. Baclofen abolished interictal activity ( n = 29 slices) and either disclosed ( n = 21/29) or prolonged ictal discharges ( n = 8/29), whereas GABA-mediated potentials occurred at a decreased rate. The N-methyl-d-aspartate (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphate (CPP, 10 μM, n = 8) did not modify the GABA-mediated potentials or the ictal events recorded in 4-AP + baclofen. In contrast ictal, activity, but not GABA-mediated potentials, was blocked by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM, n = 5). Most baclofen effects were reversed by the GABAB receptor antagonist CGP 35348 (1 mM; n = 4). Baseline and transient increases in [K+]o associated with the 4-AP–induced synchronous activity were unaffected by baclofen. Baclofen hyperpolarized CA3 pyramids ( n = 8) recorded with K-acetate–filled electrodes by 4.8 ± 1.3 mV and made spontaneous, asynchronous hyperpolarizing and depolarizing potentials disappear along with interictal depolarizations. GABA-mediated synchronous long-lasting depolarizations (LLDs) and asynchronous depolarizations were also studied with KCl-filled electrodes in 4-AP + CPP + CNQX ( n = 6); under these conditions baclofen did not reduce LLD amplitude but abolished the asynchronous events. Dentate hilus stimulation at 0.2–0.8 Hz suppressed the ictal activity recorded in 4-AP + baclofen ( n = 8). Our data indicate that GABAB receptor activation by baclofen decreases transmitter release leading to disappearance of interictal activity along with asynchronous excitatory and inhibitory potentials. By contrast, GABA-mediated LLDs and ictal events, which reflect intense action potential firing invading presynaptic inhibitory and excitatory terminals respectively, are not abolished. We propose that the proconvulsant action of baclofen results from 1) block of asynchronous GABA-mediated potentials causing disinhibition and 2) activity-dependent changes in hippocampal network excitability.

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