scholarly journals A tale of two endings: Modulation of satiation by NMDA receptors on or near central and peripheral vagal afferent terminals

2011 ◽  
Vol 105 (1) ◽  
pp. 94-99 ◽  
Author(s):  
Robert C. Ritter
Keyword(s):  
Nmda Receptors ◽  
Vagal Afferent ◽  
Afferent Terminals

NMDA channels control meal size via central vagal afferent terminals

2005 ◽  
Vol 289 (5) ◽  
pp. R1504-R1511 ◽  
Author(s):  
B. R. Gillespie ◽  
G. A. Burns ◽  
R. C. Ritter
Keyword(s):  
Food Intake ◽  
Ion Channel ◽  
Nmda Receptors ◽  
Higher Order ◽  
Meal Size ◽  
Vagal Afferents ◽  
Sucrose Intake ◽  
Mk 801 ◽  
Vagal Afferent ◽  
Afferent Terminals

The N-methyl-d-aspartate (NMDA) ion channel blocker MK-801 administered systemically or as a nanoliter injection into the nucleus of the solitary tract (NTS), increases meal size. Furthermore, we have observed that ablation of the NTS abolishes increased meal size following systemic injection of dizocilpine (MK-801) and that MK-801-induced increases in intake are attenuated in rats pretreated with capsaicin to destroy small, unmyelinated, primary afferent neurons. These findings led us to hypothesize that NMDA receptors on central vagal afferent terminals or on higher-order NTS neurons innervated by these vagal afferents might mediate increased food intake. To evaluate this hypothesis, we examined 15% sucrose intake after 50-nl MK-801 injections ipsilateral or contralateral to unilateral nodose ganglion removal (ganglionectomy). On the side contralateral to ganglionectomy, vagal afferent terminals would be intact and functional, whereas ipsilateral to ganglionectomy vagal afferent terminals would be absent. Three additional control preparations also were included: 1) sham ganglionectomy and 2) subnodose vagotomy either contralateral or ipsilateral to NTS cannula placement. We found that rats with subnodose vagotomies increased their sucrose intake after injections of MK-801 compared with saline, regardless of whether injections were made contralateral (12.6 ± 0.2 vs. 9.6 ± 0.3 ml) or ipsilateral (14.2 ± 0.6 vs. 9.7 ± 0.4 ml) to vagotomy. Rats with NTS cannula placements contralateral to nodose ganglionectomy also increased their intake after MK-801 (12.2 ± 0.9 and 9.2 ± 1.1 ml for MK-801 and saline, respectively). However, rats with placements ipsilateral to ganglionectomy did not respond to MK-801 (8.0 ± 0.5 ml) compared with saline (8.3 ± 0.4 ml). We conclude that central vagal afferent terminals are necessary for increased food intake in response to NMDA ion channel blockade. The function of central vagal afferent processes or the activity of higher-order NTS neurons driven by vagal afferents may be modulated by NMDA receptors to control meal size.

Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. III. Role of cardiac afferents

1996 ◽  
Vol 270 (5) ◽  
pp. H1785-H1790 ◽  
Author(s):  
G. Katchanov ◽  
J. Xu ◽  
C. M. Hurt ◽  
A. Pelleg
Keyword(s):  
Carotid Artery ◽  
Common Carotid Artery ◽  
Left Common Carotid Artery ◽  
Descending Aorta ◽  
Chronotropic Action ◽  
Vagal Reflex ◽  
Vagal Afferent ◽  
The Asymmetry ◽  
Cardiac Afferents ◽  
Afferent Terminals

To test the hypothesis that the asymmetry in the afferent traffic of the intra-right atrium (RA) ATP-triggered vagal reflex is due to the stimulation by ATP of extrapulmonary (i.e., cardiac) vagal chemosensitive afferent terminals, ATP, adenosine, and capsaicin were given into the canine RA and the aortic root (AR; n = 12); ATP and adenosine were also administered into the left common carotid artery and the descending aorta (n = 6). The negative chronotropic action [i.e., suppression of sinus node (SN) automaticity] of the test compounds and time to peak effect (tp) were determined. Under baseline conditions, ATP given into the left common carotid artery had a relatively very small effect. ATP given into the descending aorta had no effect. In contrast, intra-RA and intra-AR ATP markedly suppressed SN automaticity, the former less than the latter; the opposite was true for capsaicin. Intra-RA adenosine was much less potent than intra-RA ATP. The tp of intra-RA ATP and intra-RA adenosine were larger than the tp of intra-AR ATP. Pulmonary denervation did not alter the effects of intra-RAATP, intra-ARATP, or intra-AR capsaicin but almost abolished the effect of intra-RA capsaicin. Subsequent bilateral, but not left, cervical vagotomy markedly reduce the effects of ATP and eliminated the difference between the effects of ATP and adenosine. In addition, tp of intra-RA ATP and intra-AR ATP increased substantially and were similar to tp of adenosine. It was concluded that 1) ATP can stimulate vagal afferent terminals not only in the lungs but also in the heart, 2) the latter constitutes the vagal component of the negative chronotropic action of intra-RA or intra-AR ATP on SN automatically, and 3) the asymmetry in the vagal afferent traffic elicited by ATP in the heart (i.e., right vagal dominance) supersedes the symmetrical vagal afferent traffic triggered by intrapulmonary ATP.

scholarly journals Mechanisms of action of CCK to activate central vagal afferent terminals

Peptides ◽  
2008 ◽  
Vol 29 (10) ◽  
pp. 1716-1725 ◽  
Author(s):  
Richard C. Rogers ◽  
Gerlinda E. Hermann
Keyword(s):  
Mechanisms Of Action ◽  
Vagal Afferent ◽  
Afferent Terminals

scholarly journals Corticosterone inhibits vagal afferent glutamate release in the nucleus of the solitary tract via retrograde endocannabinoid signaling

2020 ◽  
Vol 319 (6) ◽  
pp. C1097-C1106
Author(s):  
Forrest J. Ragozzino ◽  
Rachel A. Arnold ◽  
Cody W. Kowalski ◽  
Marina I. Savenkova ◽  
Ilia N. Karatsoreos ◽  
...  
Keyword(s):  
Brain Stem ◽  
Autonomic Function ◽  
Glutamate Release ◽  
Vagal Afferents ◽  
Solitary Tract ◽  
Excitatory Neurotransmitter ◽  
Cannabinoid Type 1 Receptor ◽  
Glutamate Signaling ◽  
Vagal Afferent ◽  
Afferent Terminals

Circulating blood glucocorticoid levels are dynamic and responsive to stimuli that impact autonomic function. In the brain stem, vagal afferent terminals release the excitatory neurotransmitter glutamate to neurons in the nucleus of the solitary tract (NTS). Vagal afferents integrate direct visceral signals and circulating hormones with ongoing NTS activity to control autonomic function and behavior. Here, we investigated the effects of corticosterone (CORT) on glutamate signaling in the NTS using patch-clamp electrophysiology on brain stem slices containing the NTS and central afferent terminals from male C57BL/6 mice. We found that CORT rapidly decreased both action potential-evoked and spontaneous glutamate signaling. The effects of CORT were phenocopied by dexamethasone and blocked by mifepristone, consistent with glucocorticoid receptor (GR)-mediated signaling. While mRNA for GR was present in both the NTS and vagal afferent neurons, selective intracellular quenching of G protein signaling in postsynaptic NTS neurons eliminated the effects of CORT. We then investigated the contribution of retrograde endocannabinoid signaling, which has been reported to transduce nongenomic GR effects. Pharmacological or genetic elimination of the cannabinoid type 1 receptor signaling blocked CORT suppression of glutamate release. Together, our results detail a mechanism, whereby the NTS integrates endocrine CORT signals with fast neurotransmission to control autonomic reflex pathways.

scholarly journals BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals

2014 ◽  
Vol 39 (9) ◽  
pp. 1439-1454 ◽  
Author(s):  
Wenling Chen ◽  
Wendy Walwyn ◽  
Helena S. Ennes ◽  
Hyeyoung Kim ◽  
James A. McRoberts ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nmda Receptors ◽  
Primary Afferent ◽  
Afferent Terminals

scholarly journals Vagal Afferent NMDA Receptors Modulate CCK-Induced Reduction of Food Intake Through Synapsin I Phosphorylation in Adult Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2613-2625 ◽  
Author(s):  
Carlos A. Campos ◽  
Hiroko Shiina ◽  
Michael Silvas ◽  
Stephen Page ◽  
Robert C. Ritter
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Kinase Inhibitor ◽  
Synaptic Strength ◽  
Nerve Fibers ◽  
Male Rats ◽  
Synapsin I ◽  
Cellular Mechanisms ◽  
Vagal Afferent ◽  
Afferent Terminals

Abstract Vagal afferent nerve fibers transmit gastrointestinal satiation signals to the brain via synapses in the nucleus of the solitary tract (NTS). Despite their pivotal role in energy homeostasis, little is known about the cellular mechanisms enabling fleeting synaptic events at vagal sensory endings to sustain behavioral changes lasting minutes to hours. Previous reports suggest that the reduction of food intake by the satiation peptide, cholecystokinin (CCK), requires activation of N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the NTS, with subsequent phosphorylation of ERK1/2 (pERK1/2) in NTS vagal afferent terminals. The synaptic vesicle protein synapsin I is phosphorylated by pERK1/2 at serines 62 and 67. This pERK1/2-catalyzed phosphorylation increases synaptic strength by increasing the readily releasable pool of the neurotransmitter. Conversely, dephosphorylation of serines 62 and 67 by calcineurin reduces the size of the readily releasable transmitter pool. Hence, the balance of synapsin I phosphorylation and dephosphorylation can modulate synaptic strength. We postulated that CCK-evoked activation of vagal afferent NMDARs results in pERK1/2-catalyzed phosphorylation of synapsin I in vagal afferent terminals, leading to the suppression of food intake. We found that CCK injection increased the phosphorylation of synapsin I in the NTS and that this increase is abolished after surgical or chemical ablation of vagal afferent fibers. Furthermore, fourth ventricle injection of an NMDAR antagonist or the mitogen-activated ERK kinase inhibitor blocked CCK-induced synapsin I phosphorylation, indicating that synapsin phosphorylation in vagal afferent terminals depends on NMDAR activation and ERK1/2 phosphorylation. Finally, hindbrain inhibition of calcineurin enhanced and prolonged synapsin I phosphorylation and potentiated reduction of food intake by CCK. Our findings are consistent with a mechanism in which NMDAR-dependent phosphorylation of ERK1/2 modulates satiation signals via synapsin I phosphorylation in vagal afferent endings.

scholarly journals CCK-Induced Reduction of Food Intake and Hindbrain MAPK Signaling Are Mediated by NMDA Receptor Activation

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2633-2646 ◽  
Author(s):  
Carlos A. Campos ◽  
Jason S. Wright ◽  
Krzysztof Czaja ◽  
Robert C. Ritter
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Vagal Afferents ◽  
Mapk Kinase ◽  
Vagal Afferent

The dorsal vagal complex of the hindbrain, including the nucleus of the solitary tract (NTS), receives neural and humoral afferents that contribute to the process of satiation. The gut peptide, cholecystokinin (CCK), promotes satiation by activating gastrointestinal vagal afferents that synapse in the NTS. Previously, we demonstrated that hindbrain administration of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists attenuate reduction of food intake after ip CCK-8 injection, indicating that these receptors play a necessary role in control of food intake by CCK. However, the signaling pathways through which hindbrain NMDA receptors contribute to CCK-induced reduction of food intake have not been investigated. Here we report CCK increases phospho-ERK1/2 in NTS neurons and in identified vagal afferent endings in the NTS. CCK-evoked phospho-ERK1/2 in the NTS was attenuated in rats pretreated with capsaicin and was abolished by systemic injection of a CCK1 receptor antagonist, indicating that phosphorylation of ERK1/2 occurs in and is mediated by gastrointestinal vagal afferents. Fourth ventricle injection of a competitive NMDA receptor antagonist, prevented CCK-induced phosphorylation of ERK1/2 in hindbrain neurons and in vagal afferent endings, as did direct inhibition of MAPK kinase. Finally, fourth ventricle administration of either a MAPK kinase inhibitor or NMDA receptor antagonist prevented the reduction of food intake by CCK. We conclude that activation of NMDA receptors in the hindbrain is necessary for CCK-induced ERK1/2 phosphorylation in the NTS and consequent reduction of food intake.

The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity

1990 ◽  
Vol 68 (2) ◽  
pp. 325-345 ◽  
Author(s):  
P. L. R. Andrews ◽  
C. J. Davis ◽  
S. Bingham ◽  
H. I. M. Davidson ◽  
J. Hawthorn ◽  
...  
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Cytotoxic Drugs ◽  
Vagal Afferents ◽  
Laboratory Animals ◽  
Receptor Antagonists ◽  
Wide Range ◽  
Vagal Afferent ◽  
Afferent Terminals ◽  
Visceral Innervation

In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.Key words: emesis, visceral nerves, vagus nerve, ferret, plasticity, serotonin antagonists.

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