Immunohistochemical characterization of cardiac vagal preganglionic neurons in the rat

Cardiac vagal preganglionic neurons (CVN) control cardiac activity by negative chronotropic, dromotropic and inotropic effects. We attempted to characterize the distribution and neuronal properties of the CVN by using double labeling with the retrograde tracer cholera toxin B subunit (CTb) and immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) or nitric oxide synthase (NOS). Injection of CTb into the sinoatrial ganglia resulted in many retrogradely labeled of neurons in the dorsal motor nucleus of the vagus (DMV), the compact (AmC), semicompact (AmS), loose (AmL), external (AmE) formations of the nucleus ambiguus, and the intermediate zone (IZ) between DMV and the nucleus ambiguus. Almost all CTb-labeled neurons showed ChAT immunoreactivity in the DMV, AmC, AmS, AmL and IZ, but most of the CTb-labeled neurons showed no ChAT immunoreactivity in the AmE. Most of the CTb-labeled neurons were double-labeled with CGRP immunoreactivity in the AmC, AmS and AmL, but a few double-labeled neurons were found in the DMV, IZ and AmE. A few CTb-labeled neurons were double-labeled with NOS immunoreactivity only in the DMV. No TH-immunoreactive neurons were found among the CVN. These results indicate that there are four kinds of neurons among the CVN: non-cholinergic CVN in the AmE, cholinergic and CGRP-containing CVN in the AmC, AmS and AmL, and cholinergic or cholinergic and NOS-containing CVN in the DMV.     

GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function

Gamma-aminobutyric acid (GABA) antagonist (bicuculline methiodide, BIC; picrotoxin, PIC) or agonist (muscimol, MUS) microinjections were made into the dorsal motor nucleus of the vagus nerve (DMV), and effects on lower esophageal sphincter pressure (LESP), gastric motility, and gastric acid secretion were determined in chloralose-anesthetized cats. Right or left DMV sites were microinjected with BIC, PIC, MUS, or isotonic saline (140 nl) through a glass micropipette having a tip diameter of 15–21 μm. Esophageal body, LESP, and gastric fundic pressures were measured manometrically. Circular smooth muscle contractions of the antrum and pylorus were recorded with strain-gauge force transducers. Gastric acid secretion was measured every 15 min through a gastric cannula and titrated to pH 7.0. DMV microinjection sites were verified histologically. Direct BIC microinjections (0.275 or 0.550 nmol) into the DMV primarily produced a decrease in LESP (71% of all sites tested), with mean LESP changing from 23.2 ± 1.7 mmHg to 3.7 ± 0.7 mmHg (p < 0.01). Tonic LESP increases and phasic LESP contractile activity occurred less frequently. BIC-induced LESP responses were abolished by vagotomy or by microinjections of MUS (0.5 to 10 nmol) into the DMV. Direct PIC microinjection (0.232 nmol) into the DMV produced a pattern of responses similar to those observed with BIC (which were also abolished by vagotomy or by MUS microinjections into the DMV). The antrum and pylorus were also responsive to DMV microinjections of both GABA antagonists. Microinjections of BIC or PIC into the DMV produced increases in gastric circular muscle activity that occurred less frequently than LESP effects, but also were eliminated by vagotomy. The high (0.550 nmol) dose of BIC increased gastric motility significantly more often than the low dose of BIC (p < 0.05). In addition, BIC (0.550 nmol) microinjections into the DMV increased gastric secretary volume (from 0.6 ± 0.2 to 6.0 ± 2.5 ml/15 min; p < 0.01) and total titratible acid (from 34.4 ±8.9 to 86.0 ± 19.1 mEq/15 min; p < 0.01), and decreased gastric pH (from 4.63 ± 0.44 to 3.50 ± 0.49; p < 0.05). Vagotomy also eliminated the gastric secretory effects of DMV BIC. Direct microinjections of MUS into the DMV also blocked BIC- or PIC-induced changes in gastric motility and/or gastric acid secretion. Isotonic saline microinjected into the DMV did not increase basal or decrease stimulated gastric esophageal motility or gastric secretion. These data indicate that LESP, gastric motility, and gastric secretion are influenced by a tonic DMV inhibition mediated by GABA_A receptor stimulation of the DMV. Because disinhibition of these receptors clearly activates the upper gut, future work should focus on identifying the nuclei providing this synaptic input to the DMV that might be involved in the functional regulation of upper gut motor and secretory function.     

Chemosensitivity of neurons in the dorsal motor nucleus of the vagus that responded to portal infusion of hypertonic saline in rats

Neural responses in the dorsal motor nucleus of the vagus (DMV) to topical administrations of sodium and portal infusions of hypertonic saline were investigated electrophysiologically by using multibarrel electrodes in anesthetized rats. Of 102 neurons that showed antidromic response to electrical stimulation of the ventral gastric vagus or the accessory celiac vagus, 51 neurons increased and 13 neurons decreased their discharge rates in response to the electrophoretic administration of sodium. The other 38 neurons did not respond to this stimulation. The portal infusion of hypertonic saline elicited neural responses of some DMV neurons whose axons are involved into either the ventral gastric or the accessory celiac vagus. Further, effects of the topical administration and the portal infusion of hypertonic saline were examined on 33 neurons. Typical response was characterized by an increase in discharge rate responding to both of the portal infusion and the topical administration. In conclusion, the DMV neurons receiving the afferent inputs from hepatoportal osmoreceptors may have an enteroceptor function detecting the change in osmotic pressure of their environment.     

Oxytocin-immunoreactive innervation of identified neurons in the rat dorsal vagal complex

Background Oxytocin (OXT) has been implicated in reproduction and social interactions and in the control of digestion and blood pressure. OXT‐immunoreactive axons occur in the dorsal vagal complex (DVC; nucleus tractus solitarius, NTS, dorsal motor nucleus of the vagus, DMV, and area postrema, AP), which contains neurons that regulate autonomic homeostasis. The aim of the present work is to provide a systematic investigation of the OXT‐immunoreactive innervation of dorsal motor nucleus of the vagus (DMV) neurons involved in the control of gastrointestinal (GI) function. Methods We studied DMV neurons identified by (i) prior injection of retrograde tracers in the stomach, ileum, or cervical vagus or (ii) induction of c‐fos expression by glucoprivation with 2‐deoxyglucose. Another subgroup of DMV neurons was identified electrophysiologically by stimulation of the cervical vagus and then juxtacellularly labeled with biotinamide. We used two‐ or three‐color immunoperoxidase labeling for studies at the light microscopic level. Key Results Close appositions from OXT‐immunoreactive varicosities were found on the cell bodies, dendrites, and axons of DMV neurons that projected to the GI tract and that responded to 2‐deoxyglucose and juxtacellularly labeled DMV neurons. Double staining for OXT and choline acetyltransferase revealed that OXT innervation was heavier in the caudal and lateral DMV than in other regions. OXT‐immunoreactive varicosities also closely apposed a small subset of tyrosine hydroxylase‐immunoreactive NTS and DMV neurons. Conclusions & Inferences Our results provide the first anatomical evidence for direct OXT‐immunoreactive innervation of GI‐related neurons in the DMV.     

Axotomy increases NADPH-diaphorase staining in rat vagal motor neurons

Left cervical vagotomy increased NADPH-diaphorase (NADPH-d) histochemical staining in neuronal perikarya of the ipsilateral dorsal motor nucleus of the vagus (dmnX) and the rostral part of the nucleus ambiguus (nAmb). This effect appeared by 2 days, was maximal around 10 days, and declined by 30 days after vagotomy. Light and dark stained perikarya occurred in dmn X ipsilateral to the vagotomy which could not be explained on the basis of the biochemical or transmitter content of these neurons. It is unlikely that the increases of NADPH-d activity resulted from changes in cholinergic transmission since vagotomy is known to decrease cholinergic enzyme function. Since vagotomy increased both the glucose metabolic rate and NADPH-d staining of dmnX and nAmb in these experiments, it is more likely that these effects represent regenerative metabolic responses to axotomy.     

Effect of portal infusion of hypertonic saline on neurons in the dorsal motor nucleus of the vagus in the rat

Effects of hepatoportal osmo-receptive (or sodium-receptive) afferents on neurons within the dorsal motor nucleus of the vagus (DMV) were investigated electrophysiologically in urethane-chloralose anesthetized rats. Responses of 56 spontaneously active neurons to antidromic stimulation of the ventral trunk of the subdiaphragmatic vagus were recorded in the left DMV. Among them, 35 neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve (inhibitory neurons), except two neurons that were slightly excited. Effects of portal infusion of 3.6% NaCl were examined on 26 inhibitory neurons. Sixteen neurons increased their discharge rates and one neuron decreased its discharge rate in response to portal infusion of hypertonic saline. Thirty-five DMV neurons responded to electrical stimulation of the dorsal trunk of the subdiaphragmatic vagus were inhibited by electrical stimulation of the hepatic branch of the vagus. Four neurons were excited by this stimulation. Relatively smaller number of neurons (5 out of 22 inhibitory neurons) increased their discharge rates in response to portal infusion of hypertonic saline. In conclusion, the response of DMV neuron observed in this experiment was characterized by increasing the frequency of spike discharges in response to portal infusion of hypertonic saline. However, these neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve. These results suggest that the hepatoportal osmoreceptive afferents may be conveyed to the DMV via inhibitory synapses.     

Specificity of 192 IgG-saporin for NGF receptor-positive cholinergic basal forebrain neurons in the rat

A monoclonal antibody to the rat nerve growth factor (NGF) receptor, 192 IgG, accumulates bilaterally and specifically in cholinergic basal forebrain (CBF) cells following intraventricular injection. An immunotoxin composed of 192 IgG linked to saporin (192 IgG-saporin) has been shown to destroy cholinergic neurons in the basal forebrain. We sought to determine if intraventricular 192 IgG-saporin affected choline acetyltransferase (ChAT) enzyme activity in the CBF terminal projection fields. ChAT assays from 192 IgG-saporin-treated animals showed significant time-dependent decreases in ChAT activity in the neocortex, olfactory bulb and hippocampus, compared to PBS- or OKT1-saporin-injected controls. ChAT and tyrosine hydroxylase activity in the striatum was always unchanged by 192 IgG-saporin. ChAT immunohistochemistry was confirmative of major cell loss in the CBF, while other cholinergic nuclei appeared unremarkable. The data provide further evidence of the selectivity of 192 IgG-saporin in abolishing cholinergic, NGF receptor-positive CNS neurons.     

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.     

Distribution and origin of nitric oxide synthase-immunoreactive nerve fibers in the rat epididymis

Distribution of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) nerve fibers and somata in the rat epididymis and major pelvic ganglia was studied by immunohistochemical methods. In the epididymis, the supply of nNOS-IR fibers was highest in the cauda and became progressively fewer toward the caput. In the cauda and corpus, nNOS-IR fibers were distributed throughout the subepithelial tissues and around the epithelium. The pattern of distribution of vasoactive intestinal polypeptide (VIP)- and tyrosine hydroxylase (TH)-immunoreactive fibers in the epididymis was similar but the latter was generally more numerous in a given region as compared to that of nNOS-IR fibers. A population of neurons in the major pelvic ganglia were nNOS-, TH- or VIP-IR. Double-labeling studies revealed that few neurons in the major pelvic ganglia contained both nNOS-IR and TH-IR. Whereas nNOS-IR and VIP-IR appeared to co-localize in the same population of pelvic ganglion cells. Similarly, nNOS-IR fibers in the epididymis were mostly VIP-positive and TH-negative. Unilateral injection of the fluorescent tracer Fluorogold into the junction between the vas deferens and the cauda labeled a population of neurons in the right and left major pelvic ganglia, some of which were also nNOS-IR. A small number of dorsal root ganglion cells contained Fluorogold and very few expressed NOS-IR. It may be concluded that nNOS-IR nerve fibers in the rat epididymis arise mainly from neurons in the major pelvic ganglia the major of which express VIP-IR but not TH-IR. The extensive supply of nNOS-immunoreactive fibers around the epithelium and throughout the subepithelial tissues suggests that NO may be closely associated with smooth muscle contraction.     

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.     

Vagal neurons and pathways to the rat's lower viscera: An electrophysiological study

The vagal pathways to the rat's pancreas are anatomically difficult to describe. A stimulation/recording technique has been used on various segments of the vagus to trace vagal pathways to the lower viscera, and a microelectrode recording technique to locate vagal neurons of origin in the brain stem's dorsal motor nucleus (DMX). The two main pathways (right cervical vagus to dorsal celiac branch and left cervical vagus to ventral celiac branch) are supplemented by two accessory ones where each cervical vagus gives some fibers to its contralateral homologue at the diaphragmatic level. These pathways consist almost exclusively of C-fibers. Neurons of origin of the dorsal vagal trunk fibers have been identified by the collision test and occupy the caudal half of the DMX; those of the dorsal celiac branch fibers originate from the medial part of that area.     

Effect of indomethacin on the c-fos expression in AVP and TH neurons in rat brain induced by lipopolysaccharide

The aim of the present study was to investigate the effect of indomethacin on the Fos expression in arginine vasopressin (AVP)-containing neurons in the hypothalamus and tyrosine hydroxylase (TH)-containing neurons in the locus coeruleus (LC) using dual-labeled immunohistochemistry. In the hypothalamus, intraperitoneal (i.p) injection of different doses [2.5 microg/100 g, 125 microg/100 g body weight (b.w.)] of lipopolysaccharide (LPS) induced a significant Fos expression in AVP neurons in the supraoptic nucleus (SON), the magnocellular division (mPVN) and the parvocellular division (pPVN) of the paraventricular nucleus (PVN). Pretreatment with the cyclooxygenase inhibitor indomethacin (0.8 mg/100 g b.w.) significantly blocked the Fos expression in these AVP neurons induced by a low dose of LPS (2.5 microg/100 g) but had no effect on the Fos expression induced by a high dose of LPS (125 microg/100 g). Similarly, in the brain stem, a large number of TH-positive neurons in the LC expressed Fos after administration of either dose of LPS. Indomethacin prevented the Fos expression induced only by a low dose of LPS, but not by a high dose of LPS. These results suggest that the activation of AVP neurons in PVN and SON and TH neurons in LC response to immune challenge might be mediated-at least partially-by prostaglandins.     

Thyrotropin-releasing hormone-immunoreactive nerve terminals synapse on the dendrites of gastric vagal motoneurons in the rat

Thyrotropin-releasing hormone stimulates vagally mediated gastric acid secretion and motility by an undefined central mechanism in the rat. The present study sought to determine the anatomical basis for this stimulatory effect by examining the ultrastructural relationship of nerve terminals immunoreactive for thyrotropin-releasing hormone with the dendrites of gastric vagal motoneurons. A light and electron microscopic double immunostaining technique was employed using the beta subunit of unconjugated cholera toxin as a neural tracer. Cholera toxin (50 microliters, 0.25%) was injected into the ventral stomach musculature in five rats. After 72 hours' survival, animals were sacrificed by transcardiac perfusion fixation. Retrogradely transported cholera toxin was immunocytochemically localized in vagal gastric motoneurons and their dendrites in the dorsal motor nucleus of the vagus and nucleus of the solitary tract, alone or in combination with the immunocytochemical localization of thyrotropin-releasing hormone. Ultrastructural analysis of double-labeled material revealed thyrotropin-releasing hormone-immunoreactive nerve terminals making asymmetric synaptic contacts on the retrogradely labeled dendrites of vagal gastric motoneurons. Nerve terminals immunoreactive for thyrotropin-releasing hormone also made asymmetric and symmetric synaptic contacts with unlabeled dendrites of undetermined perikaryal origin. In addition, nonsynaptic varicosities immunoreactive for thyrotropin-releasing hormone were frequently observed in the vagal nuclei. The synaptic contacts between thyrotropin-releasing hormone-immunoreactive nerve terminals and vagal gastric motoneuronal dendrites provide one possible basis for the profound stimulatory effect of central thyrotropin-releasing hormone on gastric vagal motor activity.     

Immunohistochemical and biochemical analysis of serotonin and substance P colocalization in the nucleus tractus solitarii and associated afferent ganglia of the rat

In a previous study of afferent projections to the nucleus tractus solitarii (NTS), it was shown that over half of the retrogradely-labelled neurons in the nucleus raphe pallidus contained serotonin-immunoreactivity and over half of these neurons contained substance P-immunoreactivity, suggesting that these two putative neurotransmitters are colocalized in NTS-afferent neurons. The objectives of the present study were to 1) directly determine if varicosities in the NTS, the area postrema (AP), and the dorsal motor nucleus of the vagus nerve (DMN) do contain both transmitters, 2) determine if primary afferent neurons in the nodose and pretrosal ganglia might also colocalize serotonin and substance P, and 3) quantify the amount of substance P that is contained in serotonergic varicosities in the NTS. Distributions and colocalization of substance P and serotonin in the NTS were studied using dual-color immunohistochemistry, while the quantity of substance P in serotonergic varicosities was assessed by radioimmunoassay (RIA) using micropunches from the NTS of 5,7-dihydroxytryptamine-(5,7 DHT-) and vehicle-treated rats. Varicosities that contained both serotonin- and substance P-immunoreactivity were found in the NTS, the DMN, and the AP. Double-labelled varicosities were common in the NTS and DMN (i.e., qualitatively similar to the density seen in the hypoglossal nucleus and in the ventral horn of the cervical spinal cord); however, the vast majority of the varicosities in these autonomic areas only displayed immunoreactivity for one or the other of these transmitters. This paucity of doubly-labelled varicosities, in comparison to the number of singly-labelled varicosities, was reflected in the lack of a significant decrease in substance P levels as determined by RIA of micropunches taken from caudal and intermediate levels of the NTS in 5,7 DHT- and vehicle-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of electrical stimulation of the dorsal nucleus of the vagus nerve on gastric acid secretion in cats.

Electrical stimulation of 3 to 9 V, 100 impules/s 1-ms duration/impulse, applied to the right or left dorsal motor nucleus of the vagus nerve (DNV) produced a significant increase in volume, acidity, and gastric acid output in 14 cats under sodium pentobarbital anesthesia. The increase in acid output occurred during the first 15 min of stimulation or immediately after the stimulation and in some cats lasted for the next 30 min to more than 2 h. In no case did the stimulation within the DNV evoke a decrease in gastric acid secretion. Similar electrical stimulation in sites outside the DNV had no effect on gastric acid secretion. Motor effects such as opening of the mouth, movements of the tongue and whiskers, and salivation were observed to occur randomly during stimulation at sites both inside and outside the DNV zone and were not correlated with changes in gastric acid secretion. After recovery from the acute experiment, two cats were tested under chronic conditions. Electrical stimulation with low voltage applied to the previously effective electrode tips repeatedly produced an increase in the volume of secretion in one cat and an increase in both volume and acidity of secretion in the other cat. This study provided further evidence that the DNV is a secretomotor center.     

Central distribution and peripheral functional properties of afferent and efferent components of the superior laryngeal nerve: Morphological and electrophysiological studies in the rat

The central distribution of the afferent and efferent components of the superior laryngeal nerve (SLN), which in the rat is ramified into the three branches of the rostral branch (R.Br), middle branch (M.Br), and caudal branch (C.Br), was examined after application of horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA) to the proximal cut end of each branch. In addition, the afferent and efferent neural activities of each branch were recorded to investigate the functional properties. The present study provided several new findings as to the distribution of each branch and the functional properties of the SLN. The following conclusions were drawn: 1) the R.Br, containing only afferent fibers projecting to the ipsilateral lateral region of the nucleus of the solitary tract (NST), extends between slightly below the obex and the region approximately 0.6 mm rostral from the obex, and it corresponds to the interstitial subnucleus of the NST; 2) the M.Br, innervating the cricothyroid muscle, contains only efferent fibers originating ipsilaterally from the motoneurons localized within the ambiguus nucleus (Amb) and in the area ventrolateral to the Amb; and 3) the C.Br, which innervates the inferior pharyngeal constrictor muscle, contains both efferent and afferent fibers. HRP-WGA-labeled cells are distributed within both the Amb and the dorsal motor nucleus of the vagus nerve, ipsilateral to the injection site. Afferent proprioceptive fibers project to the ipsilateral interstitial subnucleus of the NST. The present results provide evidence that each branch of the SLN has distinctive functional properties and contributes to the laryngeal functions. © 1996 Wiley-Liss, Inc.     

Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat

The receptor-mediated axonal transport of [¹²⁵I]-labeled neurotrophins by afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [¹²⁵I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal afferent neurons retrogradely transported [¹²⁵I]neurotrophin-3 (NT-3), [¹²⁵I]nerve growth factor (NGF), and [¹²⁵I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [¹²⁵I]NT-3, [¹²⁵I]NGF, and [¹²⁵I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal afferent neurons showed minimal accumulation of [¹²⁵I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [¹²⁵I]BDNF, [¹²⁵I]NT-3, and [¹²⁵I]NT-4, but not [¹²⁵I]NGF. The receptor specificity of neurotrophin transport was examined by applying [¹²⁵I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [¹²⁵I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [¹²⁵I]NGF was reduced only by NGF, whereas the transport of [¹²⁵I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these visceral sensory and motor neurons in vivo. J. Comp. Neurol. 393:102–117, 1998. Published 1998 Wiley-Liss, Inc.

1 This article is a US government work and, as such, is in the public domain in the United States of America.

     

Vagal motor neurons in rats respond to noxious and physiological gastrointestinal distention differentially

Low-pressure gastrointestinal distention modulates gastrointestinal function by a vago-vagal reflex. Noxious visceral distention, as seen in an obstruction of the gastrointestinal tract, causes abdominal pain, vomiting and affective changes. Using single neuron recording and intracellular injection techniques, we characterized the neuronal responses of neurons in the dorsal motor nucleus of the vagus (DMNV) to low- and high-pressure distensions of stomach and duodenum. Low-pressure gastric distention inhibited the mean activity of the DMNV neurons whereas high-pressure gastric distention excited many neurons. Of 47 DMNV neurons, low-pressure gastric distention inhibited 39, excited four, and did not affect four neurons. High-pressure gastric distention inhibited 26, excited 20, and left one unaffected. Thirteen of the 39 DMNV neurons inhibited by low-pressure distention of the stomach reversed their response to excitation during high-pressure gastric distention. Among 47 DMNV neurons, low-pressure duodenal distention inhibited 30, excited 10, and did not affect the remaining seven neurons. High-pressure distention of the duodenum inhibited 25 and excited 22 neurons. Eight DMNV neurons inhibited by low-pressure duodenal distention were excited in early response to high-pressure distention of the duodenum. High-pressure duodenal distention caused an early excitation and late inhibition in the mean activity of the DMNV neurons while low-pressure duodenal distention only produced late inhibition. These results suggest that different reflexes are present between physiological distention and noxious stimulation of gastrointestinal tract.