Vagal Afferent Signaling Research Articles

Additive satiety-delaying effects of capsaicin-induced visceral deafferentation and NMDA receptor blockade suggest separate pathways

Both ablation of visceral afferents and blockade of NMDA receptor-mediated glutamatergic transmission by MK-801 result in overconsumption of sucrose solution and other food, apparently by interrupting visceral signals and thus delaying satiation. If these two manipulations act on the same pathway, namely, the propagation of vagal afferent signals to NTS neurons, their effects would be expected to be non-additive. To test this hypothesis, two groups of rats — one with prior systemic capsaicin ( n=11) and one with vehicle treatment ( n=10) — were trained to drink 15% sucrose solution after 15 h food deprivation every 3–4 days, and then injected with MK-801 (100 μg/kg, i.p.) or saline. Both capsaicin and MK-801 produced the expected significant ( P<.001) increase in 30 and 60 min sucrose intake if compared to their respective controls. Administration of MK-801 to capsaicin-treated rats further increased 60 min sucrose intake significantly ( P<.001) in a fully additive fashion. These results suggest that the two treatments do not impinge on the same neural pathway to delay satiation. MK-801 may interfere with signals from capsaicin-resistant vagal afferents, or alternatively may act on other areas in the brain or periphery.

Central processing of vagal afferent input from the acid-injured rat stomach: Implications for dyspepsia?

Background: Although gastric acid is a factor in upper abdominal pain caused by gastro-oesophageal reflux, gastritis, peptic ulcer and functional dyspepsia, the processing of a gastric mucosal acid insult within the central nervous system is little known. This study examined which neurons in the brain respond to challenge of the rat gastric mucosa by a noxious concentration of hydrochloric acid (HCI) and whether the central input is carried by vagal afferent neurons. Methods: Activation of central neurons was mapped via transcription of c-fos messenger ribonucleic acid (mRNA) and visualized by in situ hybridization autoradiography with a c-fos oligodesoxyribonucleic acid probe. Quantitative results were obtained by counting the number of c-fos mRNA-positive cells in 2: 5 sections (10 pm). Results: When examined 45 min after intragastric treatment of rats with HCI (0.5 M), many neurons in the nucleus of the solitary tract, lateral parabrachial nucleus, thalamic and hypothalamic paraventricular nucleus, supraoptic nucleus, central amygdala and habenula expressed c-fos mRNA as compared to intragastric treatment with saline. Some expression of c-fos mRNA was also noted in the area postrema and subfornical organ. Intragastric treatment with hypertonic saline (0.5 M) caused some expression of c-fos mRNA in medullary and hypothalamic nuclei, but the response to 0.5 M saline was only 10 30 % of that to 0.5 M HCI. The c-fos mRNA reaction to intragastric HCI in all regions was depressed by 2: 80 % five days after bilateral subdiaphragmatic vagotomy, whereas the number c-fos mRNA-positive cells in the periaqueductal grey and dorsal raphe nucleus was enhanced. Conclusions: These data show that acid-sensitive vagal afferents signal gastric acid challenge to the brainstem wherefrom the information is communicated to higher relay centres of the brain. The central processing of gastric mucosal acid insults involves nuclei that play a role in perception and in the regulation of behavioral, neuroendocrine, autonomic and antinociceptive reactions. It is anticipated that the findings have a bearing on the understanding of dyspeptic complaints. This study was supported by FWF grant P1l834-MED.

Gut vagal afferent lesions increase meal size but do not block gastric preload-induced feeding suppression.

Subdiaphragmatic vagal afferent (SVA) signals arising from gut sites may provide critical feedback for the control of food intake within a meal. To evaluate the role of SVAs in both spontaneous and scheduled meals, food intake was assessed in two paradigms in male Sprague-Dawley rats. In the first study, control (Con) rats (n = 6) and rats with subdiaphragmatic vagal deafferentation (SDA) (n = 7) had 12-h nightly access to Ensure liquid diet (1 kcal/ml). SDA rats had larger and fewer meals and maintained initial rapid rates of licking, yet total numbers of licks were unaffected. In the second study, Con (n = 8) and SDA (n = 7) rats had scheduled access to 12. 5% liquid glucose after overnight food deprivation. Glucose intake was assessed after 5-ml gastric preloads of 0.9% saline or glucose, peptone, and Intralipid solutions at three concentrations (0.5, 1, and 2 kcal/ml). Glucose and peptone preloads suppressed intake similarly in Con and SDA rats, whereas Intralipid was ineffective. These results suggest that meal-related SVA signals 1) are not critical in determining preload-induced feeding suppression after deprivation, yet 2) contribute to satiety during spontaneous meals.

Cytokine-induced anorexia. Behavioral, cellular, and molecular mechanisms.

Cytokines induce anorexia. Recent issues concerning mechanistic aspects are: (1) Cytokines induce anorexia through different modes of behavioral action, that is, by affecting meal size, meal duration, and meal frequency differentially. Profiles also depend on the concentration or dosage. (2) The interface between the periphery and brain. Specific cytokines may be transported from the periphery to the brain. Cytokines generate mediators that can act on peripheral and/or brain target sites. Cerebrovasculature endothelium can also generate signals to modulate neural activities. Evidence indicates that the proposed vagal afferent signaling requires reassessment. Because of paracrine and autocrine actions, local cytokine production within the brain can induce anorexia. (3) Cytokines act directly on hypothalamic neurons proposed to participate in feeding. (4) Cytokine<-->cytokine and cytokine<-->peptide/neurotransmitter interactions are critical; for example, cytokines interact to induce anorexia synergistically, neuropeptide Y<-->cytokine interactions are antagonist, and cytokine<-->neurotransmitter and cytokine<-->leptin<-->neuropeptide Y<-->CRH-glucocorticoid and other endocrine interactions are important. A leptin receptor is related to gp 130, a signal transducer among interleukin (IL)-6 subfamily receptors; gp 130 and related molecules may be an interface for feeding control in health and disease. Various cytokines upregulate leptin and gp 130. An integrative approach combining computerized meal pattern analyses with cellular and molecular approaches is being used to characterize mechanisms (ligands, receptors, transducing molecules, and intracellular mediators) involved in cytokine-induced anorexia.

Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal afferent signals in rat.

Volume and chemical characteristics of meals in the gut have been proposed to generate vagal afferent signals that mediate the negative feedback control of ingestion and gastric emptying. Furthermore, duodenal nutrients elicit changes in gastrointestinal motility that may stimulate mechanosensitive vagal afferents. The degree to which the activity of an individual vagal afferent fiber can be modified by moth mechanical and nutrient properties in the gut remains unclear. The present studies evaluated the relationships between distal antral and proximal duodenal load-sensitive vagal afferent activity and gastroduodenal motility in response to duodenal nutrient exposure in ketamine-xylazine-anesthetized rats. Duodenal carbohydrate (glucose) and amino acid (peptone) infusions (0.2 ml/min, 0.2-0.5 kcal/ml) stimulated concentration-dependent increases in 1) antroduodenal contractions and 2) antral and duodenal vagal afferent activity beyond those attributable to osmolarity alone. In addition, duodenal peptone was more effective than equicaloric glucose in eliciting this vagal activity. These data demonstrate that the proximal duodenum can discriminate its nutrient chemical contents and that gastroduodenal load-sensitive vagal afferents indirectly transduce nutrient chemical information.

Sub-diaphragmatic vagal afferent integration of meal-related gastrointestinal signals

We have established a method to investigate the range of mechanical, nutrient chemical and peptidergic meal-related stimuli that may generate vagal afferent neurophysiological signals critical to the negative feedback control of food intake in the rat. We have identified populations of fibers that respond with increased neurophysiological discharge rates to gastric loads, duodenal loads, and close celiac arterial administration of a brain-gut peptide, cholecystokinin. Load-sensitive fibers with gastric and duodenal mechanoreceptive fields are able to integrate information arising from mechanical and peptidergic stimulation, where cholecystokinin octapeptide (CCK) administration potentiates subsequent responses to distending loads, and synergizes with distending loads to produce greater excitation than either load stimulus alone or peptide stimulation alone. In addition, we have identified situations where the duodenal presence of nutrients modifies the vagal afferent activity of gastric load-sensitive fibers. Thus, our approach can mimic the temporal and spatial distribution of meal-related stimuli in the gut, and reveals the potential for nutrients in one gastrointestinal compartment to affect neural signals arising from another gut compartment.

Effect of Lung Inflation on Levator Veli Palatini Muscle Activity

Palatal movements play a critical role in regulating oropharyngeal airflow during breathing. We hypothesized that these movements are coordinated with breathing movements via afferent signals from the lung. However, the control of palatal movements in relation to the lung remains unclear. This study was designed to define, by electromyographic techniques, the relationship between palatal movement and lung action during respiration. We performed tracheotomies on 12 mongrel dogs anesthetized with sodium pentobarbital and found that lung inflation augmented the activity of the levator veli palatini muscle (LVP). Two kinds of discharges were recognized during the expiratory pause following lung inflation. One was a continuous, low-amplitude discharge induced during apnea following lung inflation. The other was a transient, high-amplitude discharge which appeared immediately after lung inflation. Both of these response activities were eliminated by bilateral vagotomy. We thus concluded that palatal movements, which can regulate expiratory airflow resistance and cause switching from nasal to oral airflow, are under the control of vagal afferent signals from the lung.

Projection of cardiovascular afferents to the lateral nodulus-uvula of the cerebellum in rabbits

Vagal and aortic afferent projections to the nodulus and uvula of the cerebellar vermis were examined in anesthetized and paralysed rabbits. Electrical stimulations of vagal and aortic nerves at a frequency of 1/s produced field potentials in the lateral cortical region of the contralateral nodulus-uvula with a latency of 6.5–19 ms. These potentials were negative in the molecular layer and positive in the granular layer. At a higher stimulation rate (30/s), these potentials were reduced by 60–65% of the control value. These results indicate that the lateral cortical region of the nodulus-uvula receives contralateral vagal and aortic afferent signals via climbing fibers. Electrical stimulation of vagal nerves also produced field potentials in the lateral region of the ipsilateral nodulus-uvula with a latency of 6–10.5 ms. Their laminal profile was characteristic of mossy fiber responses. At a higher stimulation rate (30/s), the reduction of these potentials was only 35%. Thus the lateral nodulus-uvula also receives the ipsilateral vagal afferent signals via mossy fibers. Following injection of horseradish peroxidase into the small areas of the lateral nodulus, labeled cells were found in bilateral intercalactus nucleus, prepositus hypogrossal nucleus, Roller nucleus, medial fascicullus longitudinalis, and medial and lateral vestibular nuclei. These nuclei may contain precerebellar neurons in the pathway from the vagal nerve to the lateral nodulus-uvula via mossy fibers.

Climbing fiber responses evoked in lobule VII of the posterior cerebellum from a vagal nerve in rabbits

The vagal afferent projection to the cerebellar posterior lobe was examined in decerebrate rabbits with electrophysiological techniques. Electrical stimulation of a vagal nerve at the cervical region evoked field potential responses on both sides of the posterior vermal cortex from lobule VI to VIII. The most prominent potentials appeared in the ipsilateral medial vermis of lobule VIIa. These potentials had a latency of 15.6 ms, and were negative in the molecular layer and positive in the granular layer. At a stimulation rate of 20 Hz, their amplitude was reduced by 70% of the control value at 1 Hz. Superimposed on these field potentials, unitary complex spikes were recorded at the depths of Purkinje cell layers. These results indicate that the medial vermal cortex of lobule VII receives vagal afferent signals via climbing fibers, which presumably convey cardiovascular information.