Lateral hypothalamus modulates gut-sensitive neurons in the dorsal vagal complex

The lateral hypothalamus (LH) regulates metabolic, behavioral and autonomic functions. The influence of the LH on gastrointestinal function and feeding behavior may be mediated by the dorsal vagal complex (DVC). In the present experiment, we used tract tracing and neurophysiologic techniques to evaluate the interrelationship between the LH and DVC. Using the tracer DiI, we demonstrated that the LH projects to both the nucleus of the solitary tract (NST) and the dorsal motor nucleus of the vagus (DMNV). We determined the effects of electrical stimulation of the LH and/or distention of the gastrointestinal tract on the firing rates of 107 DMNV neurons and 68 NST neurons. As previously reported, the majority of the DMNV neurons were inhibited and the majority of the NST neurons were excited by gastrointestinal distention. Electrical stimulation of the LH significantly changed the spontaneous activities of 71% of the DMNV neurons (46 excited and 30 inhibited). Of the 68 NST neurons characterized, 25 neurons were inhibited and 8 were excited by LH stimulation. In a separate experiment, we characterized the effects of both electrical and chemical stimulation of the LH on 36 DMNV and 14 NST neurons. Glutamate (0.8 nM) induced similar responses in the DVC neurons as electrical stimulation of the LH. The results indicate that the LH influences the electrical activity of DVC neurons. This effect may be the mechanism by which the LH modulates gastrointestinal function and feeding behavior.     

Relationships between the morphology and function of gastric and intestinal distention-sensitive neurons in the dorsal motor nucleus of the vagus

The activity of vagal motor neurons is influenced by sensory information transmitted to the brainstem. In particular, there is evidence that distention of the stomach increases activity of motor neurons in the dorsal vagal motor nucleus, whereas distention of the duodenum, small intestine, and colon reduces neuron firing. In this study, we determined 1) the response of vagal motor neurons to distention of the stomach and duodenum and 2) whether the response properties were associated with specific morphological features. Using the single-cell recording and iontophoretic injection technique, we identified four groups of vagal motor neurons affected by gastric and/or duodenal distention. Group 1 neurons responded to either gastric or duodenal stimulation. Neurons in groups 2, 3, and 4 were affected by both gastric and duodenal distention. Group 2 neurons were excited by duodenal distention and were inhibited by gastric distention. Group 3 neurons were inhibited by duodenal distention and were excited by gastric distention. Most neurons belonged to group 4. Neurons in this group were inhibited by both gastric and duodenal distention. Our analyses revealed that the neurons affected by both stimuli had distinctive structural features. Neurons in group 2 had the largest somata, the most dendritic branches, and the greatest cell surface area. Neurons in group 3 were the smallest and had the shortest dendritic length. In addition, we were able to demonstrate that the neurons in group 4 had a smaller total dendritic length and a smaller cell volume than neurons in group 2 and had more dendritic branch segments than neurons in group 3. These results suggest that morphological features are associated with specific response properties of vagal motor neurons. © 1996 Wiley-Liss, Inc.     

Relationships between the morphology and function of gastric- and intestine-sensitive neurons in the nucleus of the solitary tract

This study employed single cell recording and intracellular iontophoretic injection techniques to characterize and label gastric- and/or intestine-sensitive neurons in the rat nucleus of the solitary tract (NST). It was possible to divide our sample of NST neurons into three broad groups based on their response to increased intra-gastric and intra-duodenal pressure. Group 1 cells (N=14) were excited by duodenal distention but were not responsive to gastric stimulation. Most of these intestine-sensitive neurons exhibited a delayed tonic response to the stimulus. Group 2 neurons (N=13) were excited by gastric distention but were not sensitive to distention of the duodenum. The typical Group 2 neuron evidenced a rapid, phasic response to the distention stimulus. Group 3 neurons (N=29) responded to both gastric and duodenal stimulation. We found that the Group 2 neurons had greater dendritic length and more dendritic branch segments than the Group 1 or Group 3 neurons. Most of the Group 1 neurons were found in the subpostremal/commissural region of the NST, while the majority of the Group 2 neurons were in the gelatinous subnucleus and a disproportionate number of the Group 3 neurons were located in the medial subnucleus. The results of this investigation demonstrate that (1) there are relationships between the morphology and physiology of distention-sensitive neurons in the NST, and (2) there are distinct functional differences between the gelatinous, medial and commissural subnuclei of this nucleus. © 1995 Wiley-Liss, Inc.     

Involvement of glutamate in gastrointestinal vago-vagal reflexes initiated by gastrointestinal distention in the rat

Vago-vagal reflexes play an integral role in the regulation of gastrointestinal function. Although there have been a number of reports describing the effects of various stimuli on the firing rates of vagal afferent fibers and vagal motor neurons, little is known regarding the neurotransmitters that mediate the vago-vagal reflexes. In the present work, we investigated the role of glutamate in the vago-vagal reflex induced by gastrointestinal distention. Using single-cell recording techniques, we determined the effects of gastric and duodenal distention on the firing rates of gut-related neurons in the dorsal vagal complex, in the absence and presence of glutamate antagonists. Kynurenic acid, a competitive glutamate receptor antagonist, injected into the dorsal vagal complex, blocked the neuronal response of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract to gastrointestinal distention. Injection of glutamate into the nucleus of the solitary tract produced inhibition of dorsal motor nucleus of the vagus neurons that were also inhibited by gastric and/or duodenal distention. Thus, the distention-induced inhibition of dorsal motor nucleus of the vagus neurons may be mediated by glutamate-induced excitation of gut-related nucleus of the solitary tract neurons. To investigate the role of the various glutamate receptor subtypes in the distention-induced events, we studied the effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, and DL-2-amino-5-phosphonopentanoic acid (DL-AP5), a selective NMDA receptor antagonist. CNQX injected into the dorsal vagal complex either blocked or attenuated the inhibitory response of the neurons in the dorsal motor nucleus of the vagus and nucleus of the solitary tract neurons to gastric and duodenal distention. In contrast, DL-AP5 had less effect, especially in the vago-vagal reflex elicited by gastric distention. The results suggest (1) distention activates vagal afferents in the gastrointestinal tract; (2) the central branches of the vagal afferents from the gut terminate in the nucleus of the solitary tract and release glutamate that mainly act on non-NMDA receptors; (3) glutamate activates the inhibitory neurons in the nucleus of the solitary tract that project to the dorsal motor nucleus of the vagus; and (4) the inhibitory neurotransmitter suppresses the activity of the dorsal motor nucleus of the vagus neurons. For the excitatory neuronal responses of the dorsal motor nucleus of the vagus neurons to gastrointestinal distention, the possible circuit is that the vagal afferents containing glutamate directly activate the receptors on the dendrites of the dorsal motor nucleus of the vagus.     

Vagal innervation of the rat duodenum

Electrophysiologic and anterograde tract tracing studies have demonstrated that the vagus nerve innervates the duodenum. These studies, however, have provided little information regarding the finer anatomic topography within the vagal complex. In this study, the retrograde neuronal tracers WGA-HRP or DiI, applied to the duodenum, were used to characterize the vagal afferent and efferent innervation of this portion of the gastrointestinal tract. This approach labeled a substantial number of motor neurons in both the medial and lateral columns of the dorsal motor nucleus of the vagus (DMNV). Vagal motor neurons innervating the duodenum were seen across the medial-lateral extent of the DMNV and between 600 microm rostral to obex and 1600 microm caudal to obex. The three branches of the vagus nerve contained efferent fibers to the duodenum. The gastric branch of the vagus nerve was the pathway that connected the majority of DMNV neurons with the duodenum. These neurons were located in the medial and middle thirds of the DMNV. The celiac branch to the duodenum was composed of axons from the majority of lateral column neurons but also contained axons from neurons in the medial column. The hepatic branch of the vagus nerve contained only a small number of cell axons. Some neurons were located medially whereas others were in the lateral third of the duodenum. Although central terminations of vagal primary afferents from the duodenum were not found in previous tract tracing studies, we observed a large number of terminals in the subpostremal/commissural region of the nucleus of the solitary tract. Similar to the motor fibers, most afferent fibers from the duodenum were located in the gastric branch of the vagus nerve, although the hepatic and celiac branches also contained afferent neurons. These results demonstrate that the vagal innervation of the duodenum is unique, being an amalgam of what would be expected following labeling of more proximal and distal portions of the GI tract. The uniqueness of the sensory and motor innervation to the duodenum has implications for hypotheses regarding the organization of vagovagal reflexes controlling gastrointestinal function.     

Physiology and morphology of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract that are sensitive to distension of the small intestine.

We have recently shown that distension-sensitive vagal afferents are part of a neural circuit affecting absorption of water in the rat small intestine. Our results indicated that vagal afferent activity directly or indirectly influences the activity of neurons in the dorsal motor nucleus of the vagus (DMNV). In the present study we pursued this interaction by examining the structure and function of neurons in the DMNV and nucleus of the solitary tract (NST) that responded to moderate distension of the small intestine. Distension-sensitive cells were filled by intracellular iontophoretic injection of horseradish peroxidase. A total of 43 distension-sensitive brainstem neurons were successfully characterized and labeled. Sixteen of the 17 NST neurons were excited by distension of the small intestine. Ten of the seventeen were restricted to the ipsilateral NST. Only two NST neurons possessed axons that terminated in the subjacent DMNV. In contrast to the response profile of the NST neurons, 24 of 26 DMNV neurons were inhibited by intestinal distension. Fourteen of the DMNV neurons appeared to contribute to the vagus nerve and 15 extended dendrites into the overlying NST. We propose that distension-induced inhibition of DMNV activity is accomplished by inhibitory NST neurons, which synapse on the dendrites of DMNV neurons in the NST.     

Nitric oxide released by gastric mechanoreceptors modulates nicotinic activation of coeliac plexus neurons in the rabbit

The effects on the nicotinic activation of the coeliac plexus neurons of nitric oxide (NO) released within the coeliac plexus by gastric mechanoreceptors, in particular during gastroduodenal inhibitory reflex, were assessed. This study was performed in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and the duodenum. The electrical activity of ganglionic neurons was recorded with intracellular recording techniques. Water-filled balloons were used for gastric distensions and recording of duodenal motility. When a 10-s train of pulses (20-40Hz) of supramaximal intensity was applied to the splanchnic nerves, gradual depression of nicotinic activation occurred. Gastric distension (50 mL, 7.5 min) modulated this depression phenomenon by inhibiting or facilitating the nicotinic activation. In the neurons impaled during the recording of duodenal motility, gastric distension triggered an inhibition of nicotinic activation concomitantly with a gastroduodenal inhibitory reflex organized by the coeliac plexus. If the gastric distensions were performed while the coeliac plexus was superfused by a NO scavenger, the nicotinic activation was unaffected and the gastroduodenal inhibitory reflex was abolished. Moreover, when the coeliac plexus was superfused with an inhibitor of nitric oxide synthase, gastric distensions were without effect on the nicotinic activation. These results demonstrate that NO released within the coeliac plexus by gastric mechanoreceptors, in particular during the gastroduodenal inhibitory reflex, modulates the central nicotinic activation of coeliac plexus neurons, so NO released within a prevertebral ganglion by gastric afferent fibres, in particular during the organization by this ganglion of a reflex regulating the gastrointestinal tract motility, also exerts a gating of the central inputs to the ganglionic neurons.     

Melanocortin‐4 receptor expression in a vago‐vagal circuitry involved in postprandial functions

Vagal afferents regulate energy balance by providing a link between the brain and postprandial signals originating from the gut. In the current study, we investigated melanocortin‐4 receptor (MC4R) expression in the nodose ganglion, where the cell bodies of vagal sensory afferents reside. By using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found GFP expression in approximately one‐third of nodose ganglion neurons. By using immunohistochemistry combined with in situ hybridization, we also demonstrated that ∼20% of GFP‐positive neurons coexpressed cholecystokinin receptor A. In addition, we found that the GFP is transported to peripheral tissues by both vagal sensory afferents and motor efferents, which allowed us to assess the sites innervated by MC4R‐GFP neurons. GFP‐positive efferents that co‐expressed choline acetyltransferase specifically terminated in the hepatic artery and the myenteric plexus of the stomach and duodenum. In contrast, GFP‐positive afferents that did not express cholinergic or sympathetic markers terminated in the submucosal plexus and mucosa of the duodenum. Retrograde tracing experiments confirmed the innervation of the duodenum by GFP‐positive neurons located in the nodose ganglion. Our findings support the hypothesis that MC4R signaling in vagal afferents may modulate the activity of fibers sensitive to satiety signals such as cholecystokinin, and that MC4R signaling in vagal efferents may contribute to the control of the liver and gastrointestinal tract. J. Comp. Neurol. 518:6–24, 2010. © 2009 Wiley‐Liss, Inc.     

Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat

Background Intestinal motilin is known to stimulate gastrointestinal (GI) motility and the arcuate nucleus (Arc) of hypothalamus is shown to be involved in the regulation of GI motility. Methods Single unit discharges in the Arc were recorded extracellularly by implantation of a force transducer into the stomach in rats, to evaluate the effect of motilin on gastric motility. Projection of nerve fiber and expression of motilin were observed by retrograde tracer deposits of Fluoro‐Gold (FG) and fluo‐immunohistochemistry staining. Key Results 65.5% of neurons in Arc responded to gastric distension (GD), 55.6% of which showed excitation (GD‐E), and 44.4% showed inhibition (GD‐I). After GD, the firing rate of GD‐E neurons significantly increased (P < 0.01), but decreased for GD‐I neurons (P < 0.01). Most of both GD‐E and GD‐I neurons were activated by motilin (P < 0.05). The frequency and amplitude of gastric contractions significantly increased by administration of motilin in Arc with a dose dependent manner (P < 0.05–0.01). However, pretreatment with GM109 could abolish the responses of neurons and excitatory effect of gastric motility induced by motilin. Motilin immunoreactive neurons were increased in Arc via gastric distention (P < 0.05). Motilin/FG‐labeled neurons were detected in hypothalamus paraventricular nucleus (PVN). Conclusions & Inferences Our findings suggest that motilin neurons in Arc may accept peripheral somatosensory afferent inputs from gastric mechanoreceptors of the stomach, and also may acts as a stimulatory factor in Arc to regulate gastric motility via some inferior nucleus relay pathway. The results provide insight into the role of Arc in the control of digestion mediated via motilin.     

Units in tegmental nuclei responding to stimulation of gastric vagal and greater splanchnic fibers in the cat

The response of neurons in the ventral and dorsal tegmental nuclei during electrical stimulation of the gastric vagal fibers which serve the proximal stomach and the left greater splanchnic fibers were evaluated in chloralose-anesthetized cats. The mean latency of 181 gastric vagally evoked unitary responses recorded in the tegmental nuclei was 352.2 ms, whereas the latency of the left greater splanchnic-evoked tegmental response was significantly less (63.2 ms). The unitary responses to the gastric vagal and greater splanchnic fibers stimulation were bilaterally distributed in the ventral and dorsal tegmental nuclei. Convergence of the gastric vagal input from the proximal stomach and the left greater splanchnic input was observed in 151 units (83 percent). Stimulation of the greater splanchnic nerve usually resulted in a short latency excitation followed by an inhibitory effect on gastric vagally evoked responses. The results suggested that some convergent splanchnic inhibition of gastric vagally evoked responses was mediated via an interneuron. Projections from the nucleus tractus solitarius and the parabrachial nucleus to the tegmental nuclei were also identified electrophysiologically by direct microstimulation of the two former areas. The significant number of gastric vagal and splanchnic evoked unitary responses recorded in the ventral and dorsal tegmental nuclei suggested that they may serve as an important pontine site for processing of visceral information between the nucleus tractus solitarius and forebrain sites.     

Simultaneous labeling of vagal innervation of the gut and afferent projections from the visceral forebrain with dil injected into the dorsal vagal complex in the rat.

The vagal innervation of the different layers of the rat gastrointestinal wall was identified with the fluorescent carbocyanine dye Dil, injected into the dorsal motor nucleus of the vagus (dmnX). Multiple, bilateral injections were used to label all dmnX preganglionic motoneurons, and as a consequence, most of the vagal primary afferents that terminate in the adjacent nucleus of the solitary tract (nts) were also retrogradely and transganglionically labeled. With Fluorogold used to label the enteric nervous system completely and specifically, the Dil-labeled vagal profiles could be visualized and quantified in their anatomical relation to the neurons of the myenteric and submucous ganglia. In the myenteric plexus, vagal fibers and terminals were found throughout the gastrointestinal tract as far caudal as the descending colon, but there was a general decreasing proximodistal gradient in the density of vagal innervation. All parts of the gastric myenteric plexus (fundus, corpus, antrum), as well as the proximal duodenum, were extremely densely innervated, with vagal fibers and terminals in virtually every ganglion and connective. Further caudally, both the percentage of innervated myenteric ganglia and the average density of label within the ganglia rapidly decreased, with the exception of the cecum and proximal colon, where up to 65% of the ganglia were innervated. In the gastric and duodenal submucosa very few and in the mucosa no vagal fibers and terminals were found. With both normal epifluorescence and laser scanning confocal microscopy, highly varicose or beaded terminal structures of various size and geometry could be identified. The Dil injections, which impregnated the dmnX as well as the adjacent nts, resulted in retrograde and anterograde labeling of all the previously reported forebrain connections with the dorsal vagal complex. We conclude that the myenteric plexus is the primary target of vagal innervation throughout the gastrointestinal tract, and that its innervation is more complete than previously assumed. In contrast, vagal afferent (and efferent) innervation of mucosa and submucosa seems conspicuously sparse or absent. Furthermore, the use of more focal injections of Dil offers the prospect to simultaneously identify specific subsets of vagal preganglionics and their central nervous inputs.     

As the gut ages: timetables for aging of innervation vary by organ in the Fischer 344 rat

To explore the effects of aging on the vagal innervation of the gastrointestinal (GI) tract, male Fischer 344 rats at 3 and 24 months of age were injected in the left nodose ganglion with 3 microl of either 4% wheat germ agglutinin-horseradish peroxidase (to label sensory endings) or 1% cholera toxin subunit B-horseradish peroxidase (to label motor endings). The stomach and duodenum were prepared as wholemounts and processed with tetramethyl benzidine. In addition, to study age-related changes in the myenteric plexus, the stomachs, small intestines, and large intestines from 3-, 12-, 21-, 24- and 27-month-old rats were prepared as wholemounts and processed with Cuprolinic Blue (to stain the neurons). Vagal afferent endings, motor terminal profiles, and myenteric neurons were counted and mapped with a sampling grid. In the stomach, both the vagal and myenteric innervation were stable between the ages of 3 and 24 months; however, a decrease in the number of myenteric neurons in the forestomach was noted at 27 months. In the small and large intestines, myenteric cell loss occurred by 12 months of age, progressed with age, and appeared to be governed by several general principles: (1) the rate of cell loss was organ-specific, with a gradient of increasing severity from proximal to distal in the gut; (2) within organs of the GI tract, the rate of cell loss differed between regions; and (3) for given regions, cell losses progressed linearly with increasing age. The findings suggest that a positive relationship exists between the density of vagal extrinsic innervation and myenteric neuron survival; however, whether this results from the vagal innervation and/or other factor(s) protecting or rescuing myenteric neurons from age-related attrition remains to be determined.     

Gastrointestinal Electrical Activity in the Prairie Dog During Fasting, Feeding, and After High-Cholesterol Diet

This study describes the electromyographic characteristics of the gastrointestinal tract of prairie dogs, and examines the effects of a 1.2% cholesterol diet on intestinal myoelectrical activity. Twelve prairie dogs were implanted with eight bipolar electrodes in the stomach and small bowel. Recordings were obtained during fasting (n = 12), gastric instillation of food (n = 7), and chronic cholesterol feeding for 3 weeks (n = 7). Gastric slow waves had a frequency per minute of 4.9 ± 1. Intestinal slow waves had a frequency per minute of 19.1 ± 2 in the duodenum, and of 16.8 ± 1 in the ileum. The migrating myoelectric complex (MMC) was identified, with an interval between two consecutive phases I of 145 ± 33 minutes. The delivery of diets of equal weight into the stomach interrupted fasting activity for approximately 3 hours. This was followed by a duodenal phase III and return of the fasted pattern. The interval between the first two postprandial phases I of the MMC not only was shorter than in the fasted state, but also was shorter after cholesterol diet than after regular diet (89 ± 33 min versus 116 ± 24 min, p ≤ 0.05). Chronic feeding of cholesterol diet did not affect the length of the MMC. In conclusion, the gastrointestinal tract of prairie dogs exhibits slow waves, spike bursts, and an MMC that is interrupted by feeding. High-cholesterol diet does not induce significant changes in the pattern of electrical activity.     

Capsaicin-Sensitive Vagal Afferent Fibers and Gastric Motility: Evidence for an "Axon Reflex" Mechanism

The role of capsaicin-sensitive afferent fibers in gastric motility has been studied in normal rats and in rats treated at birth with the sensory neurotoxin capsaicin, a procedure known to destroy up to 90% of unmyelinated afferent fibers. Gastric motility was measured as intragastric pressure changes evoked by the distention of the stomach with 8 to 10 ml of normal (154 mM) or 1 M saline solution. No differences were observed between the motility patterns evoked by gastric distention with these two solutions. Distention of the stomach evoked a significantly lower basal tone and a reduced number and amplitude of phasic contractions in capsaicin-treated rats compared to control rats. Intravenous administration of the ganglionic blocker hexamethonium substantially reduced phasic motility in both groups of animals. Subsequent bilateral vagotomy had little extra effect. After bilateral vagotomy, electrical stimulation at supramaximal intensities of the peripheral end of the cut right vagus in the presence of hexamethonium produced an inhibition of the gastric basal tone in both groups of rats and, on cessation of stimulation, a series of rebound contractions in most control animals, but not in those treated at birth with capsaicin. These results provide evidence for an efferent role of vagal afferent fibers in the control of gastric motility, possibly via an axon reflex mechanism.     

Ultrastructural localization of serotonin 2A and N-methyl-D-aspartate receptors in somata and dendrites of single neurons within rat dorsal motor nucleus of the vagus

Both glutamate and serotonin are potent modulators of autonomic functions involving the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMNV) at the level of the area postrema. Moreover, many of the dendrites in this NTS region express both N-methyl-D-aspartate (NMDA) and serotonin (5HT) 2A receptors, and some of these dendrites may arise from the adjacent DMNV. Thus, single neurons in DMNV may also express both receptors. To test this hypothesis, we used electron microscopic immunocytochemistry for dual localization of the essential R1 subunit of the NMDA receptor (NR1) and the 5HT2A receptor in rat intermediate DMNV, a region serving mainly gastrointestinal functions. Gold particles representing NR1 and peroxidase reaction product for 5HT2A receptors were seen in the cytoplasm, as well as on distinct segments of the plasma membrane of many dendrites. Of the NR1-labeled dendrites, 31% (254/814) also contained 5HT2A immunoreactivity; among the 5HT2A-labeled dendrites, 52% (254/485) expressed NR1. The 5HT2A labeling was also present in numerous small unmyelinated axons, axon terminals, and glial processes. These profiles were largely without NR1 immunoreactivity, although NR1 was detected in some of the dendrites postsynaptic to 5HT2A-labeled terminals. Our results suggest that calcium entry through NMDA channels and 5HT2A receptor activation may dramatically affect postsynaptic excitability of single neurons in the DMNV. In addition, the findings also indicate that the 5HT2A receptor is strategically positioned for involvement in modulation of the presynaptic release of neurotransmitters affecting the postsynaptic activity of DMNV neurons responsive to NMDA activation.     

GABA as an autonomic neurotransmitter: studies on intrinsic GABAergic neurons in the myenteric plexus of the gut

Outside the CNS, no part of the nervous system approaches the structural and functional complexity of the enteric ganglia of the gastrointestinal tract. Recently, it has become evident that there is a population of GABAergic neurons within the myenteric ganglia in the stomach, duodenum, ileum, colon and caecum. The GABAergic neurons of the gut nervous system project not only to other neurons within the myenteric ganglia, but also out into the circular muscle coat of the gut wall. Their presence has important implications for the intrinsic neuronal control of gastrointestinal function.     

Vago-sympathetic modulation of gastric mechanoreceptors: Effect of distention and nutritional state

Summary Unit discharge evoked in gastric afferents by tactile stimulation of the frog's stomach was inhibited by electrical stimulation of gastric vagi and facilitated by cervical sympathetic stimulation. The inhibition or the facilitation of the evoked response depended on the mode and parameters of stimulation used. The tactually-evoked activity was also inhibited by gastric distention in well-fed animals (Type-I). This inhibition was released by gastric vagotomy, while cervical sympathectomy had no appreciable effect on the evoked inhibitory response.In Type-II animals (animals kept on chronic food deprivation) the tactually-evoked activity was facilitated, rather than inhibited, by coupling tactile stimulation with gastric distention. This facilitation was abolished by cervical sympathectomy, but was not significantly affected by gastric vagotomy. It appears that the differential modulating control of gastric mechanoreceptor activity is biased by the state of energy balance and is brought about by a dual efferent control system mediated through autonomic nerves, gastric vagal fibers being inhibitory, and cervical sympathetic nerves being facilitatory to the tactile response.This investigation was supported by PL-480 Grant NIH-01-015-1.     

Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by cAMP levels

Abstract  Pancreatic polypeptides such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility. Vagal efferent outflow to the GI tract is determined principally by tonic GABAergic synaptic inputs onto dorsal motor nucleus of the vagus (DMV) neurons, yet neither peptide modulates GABAergic transmission. We showed recently that opioid peptides appear similarly ineffective because of the low resting cAMP levels. Using whole cell recordings from identified DMV neurons, we aimed to correlate the influence of brainstem cAMP levels with the ability of pancreatic polypeptides to modulate GABAergic synaptic transmission. Neither NPY, PYY, nor the Y1 or Y2 receptor selective agonists [Leu,Pro]NPY or NPY(3-36) respectively, inhibited evoked inhibitory postsynaptic current (eIPSC) amplitude unless cAMP levels were elevated by forskolin or 8-bromo-cAMP, by exposure to adenylate cyclase-coupled modulators such as cholecystokinin octapeptide (sulfated) (CCK-8s) or thyrotropin releasing hormone (TRH), or by vagal deafferentation. The inhibition of eIPSC amplitude by [Leu,Pro]NPY or NPY(3-36) was stable for approximately 30 min following the initial increase in cAMP levels. Thereafter, the inhibition declined gradually until the agonists were again ineffective after 60 min. Analysis of spontaneous and miniature currents revealed that such inhibitory effects were due to actions at presynaptic Y1 and Y2 receptors. These results suggest that, similar to opioid peptides, the effects of pancreatic polypeptides on GABAergic transmission depend upon the levels of cAMP within gastric inhibitory vagal circuits.     

Investigation of catecholamine effects on stomach and duodenum motor functions in unanaesthetized dogs

The aim of this study was to investigate the effects of catecholamines on motility of stomach and intestine in chronic experiments on dogs with fistulas in stomach and duodenum. The contractions of stomach and duodenum were registered by a balloon method. It was established that i.v. adrenaline and noradrenaline injections in dogs with intact vagi inhibited food-induced motility in stomach and duodenum and did not produce contractions in the empty and quiescent gastrointestinal tract. Beta-adrenoagonist isoprenaline on the contrary produced stomach and duodenum contractions in fed dogs during the quiescent period. In fed dogs isoprenaline caused a 3-phasic reaction: a phase of primary short-term suppression of stomach and duodenum motility, a phase of motility increase and a phase of secondary suppression of stomach and duodenum motility. The contractions evoked by isoprenaline in the stomach resemble in amplitude and shape, periodical activities which are typical for fasting dogs. Vagotomy intensified isoprenaline motor effects in hungry and fed dogs and eliminated the phase of primary suppression in fed dogs. The isoprenaline effects were blocked by propranolol, but not by phentolamine. They were decreased more effectively in the stomach by atropine and by hexomethonium in the duodenum.