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Anatomy of the gustatory system in the hamster: synaptology of facial afferent terminals in the solitary nucleus.

The solitary nucleus is the first level of the central nervous system where processing of taste information can occur. A structural basis for that processing was investigated. Facial taste afferent axons were labelled by application of horseradish peroxidase to either the chorda tympani or the geniculate ganglion. The labelled afferent fibers in the rostral solitary nucleus were studied with light and electron microscopy. Preterminal facial taste afferent axons enter the nucleus from the solitary tract with a pronounced lateral to medial trajectory. The axons bear numerous preterminal and terminal swellings that, with the electron microscope, were identified as synaptic endings located in glomeruli. The endings are ovoid or scalloped, indented by structures that surround them. The primary afferent endings contain large, round vesicles and synapse, by means of slightly asymmetrical junctional complexes, on small dendrites and spines. Two types of unlabelled endings, surrounding the labelled ones, contact the dendrites receiving taste afferent input or contact the endings of taste afferent axons themselves. One type is variable in size and contains scattered large round vesicles. It resembles a presynaptic dendrite. The other is a small axonal ending packed with small, pleomorphic vesicles, that engages in symmetrical junctions. The synaptic milieu of the taste endings allows for the possibility of modulation of taste-elicited activity in afferent endings or second-order neurons by other, possibly interneuronal, inputs.

Animals↗

Taste-responsive neurons and their locations in the solitary nucleus of the hamster.

The solitary nucleus (nucleus tractus solitarii), the first central relay for taste in mammals, was studied anatomically and physiologically in the golden hamster (Mesocricetus auratus). Activity of neurons to anterior tongue stimulation with sucrose, NaCl and KCl were extracellularly recorded. Electrolytic lesions or horseradish peroxidase deposits allowed subsequent localization of recording sites. Anterior tongue taste-responsive sites were restricted to a very small part of the rostral pole of the solitary nucleus, which is about 3% of the entire nucleus. Sites were confined to the rostral-central and rostral-lateral subdivisions of Whitehead, which contain a number of morphological cell types. Some chemotopic organization was seen with multi-unit recordings, with NaCl-selective sites concentrated rostrally and sucrose- and KCl-selective sites concentrated caudally. Sites with broad sensitivity were distributed throughout the gustatory region. Single neural units showing inhibition to taste stimuli, units highly reactive to all three stimuli, and units with high spontaneous rates were seen in the solitary nucleus, as well as units that responded very selectively and had low spontaneous rates. Single units with similar response profiles to sucrose, NaCl and KCl were not segregated to separate restricted locations within the taste-reactive region; their distributions overlapped. In the hamster, neurons in the anterior tongue taste region of the solitary nucleus process taste quality information in diverse ways. Highly reactive non-specific neurons, neurons that show inhibition, and neurons with high spontaneous rates are more frequently observed in the solitary nucleus than in the afferent input fibers of the chorda tympani nerve. The small region of the rostral pole enclosing taste-responsive neurons is complexly organized in relation to taste quality and contains a number of morphological cell types whose functional role in taste is not yet known.

Action Potentials↗

Comparison of volume-conducted far-field short-latency glossopharyngeal nerve evoked potentials recorded from the scalp with similarly obtained near-field potentials from the solitary nucleus in dogs.

In 11 dogs, potentials recorded from the scalp and from the solitary nucleus after stimulation of the glossopharyngeal nerve were compared. The far-field potentials recorded from the scalp consisted of negativity, with peak latency of 2.10 to 3.45 milliseconds (mean, 2.93 milliseconds), followed by positivity, with peak latency of 3.20 to 5.95 milliseconds (mean, 4.86 milliseconds) and duration of 4.65 to 6.95 milliseconds (mean, 5.70 milliseconds). The near-field potentials recorded from the solitary nucleus consisted of positivity, with peak latency of 2.15 to 2.70 milliseconds (mean, 2.45 milliseconds), followed by negativity, with peak latency of 4.05 to 5.05 milliseconds (mean, 4.39 milliseconds) and duration of 4.45 to 5.80 milliseconds (mean, 5.21 milliseconds). Comparison of the far-field potentials (n = 10) with the near-field potentials (n = 5) indicated that polarity of the waves was reversed and that the first peak's latency was slightly (approx 0.5 milliseconds) longer in the scalp-recorded far-field potentials. Neither the difference in latency of the second peak nor the difference in its duration, measured from the onset of the potentials to the return to the baseline of the activity, was significant. The results strongly suggest that the response in the solitary nucleus evoked by electrical stimulation of the glossopharyngeal nerve is the source of at least part of the scalp-recorded responses to stimulation of the same nerve. The scalp-recorded far-field potentials could, therefore, be characterized as volume conducted from the evoked response in the solitary nucleus.

Animals↗

Relays from the spinal cord and solitary nucleus through the parabrachial nucleus to the forebrain in the cat.

Projections from the spinal cord and solitary nucleus to the lateral parabrachial nucleus (PBN1) in the cat were directly compared using double anterograde tracing methods. The two inputs were found to overlap within a well-circumscribed zone in the rostral 2/3 of PBN1. This zone was flanked ventrally by a zone receiving only solitary nucleus input and dorsally by a zone receiving only spinal input. Other authors have shown that neurons within these three recipient zones (overlap area, solitary nucleus and spinal cord) project to different forebrain targets (hypothalamus, amygdala and thalamus, respectively). This orderly input-output organization is likely to provide part of the framework for PBN's complex involvement in the coordination of respiratory and cardiovascular activities and their association with pain, visceral sensation and emotion.

Afferent Pathways↗

Capsaicin in the 4th ventricle abolishes retching and transmission of emetic vagal afferents to solitary nucleus neurons.

Systemic tachykinin NK1 receptor antagonists and resiniferatoxin are known to abolish vomiting mediated by vagal afferents. Emetic vagal afferents have been shown to make synaptic contact with neurons in the medial solitary nucleus. These results suggest that substance P participates in the synapse as a mediator. To examine this possibility, the effects of 4th-ventricular application of capsaicin (0.033-33 mM, 20-30 microl) and resiniferatoxin (1.6-160 microM, 20-30 microl) on the activity of neurons in the medial solitary nucleus and fictive retching induced by vagal stimulation were observed in paralyzed decerebrate dogs. Capsaicin (33 mM) and resiniferatoxin (160 microM) initially increased the neuronal firing and occasionally produced retching, then abolished both neuronal and retching responses. However, stimulation of the medial solitary nucleus continued to provoke retching. Field potential changes in the medial solitary nucleus evoked by pulse-train vagal stimulation decreased in amplitude, but did not disappear. Latencies of neuronal firing and evoked potentials were about 300 ms. These results suggest that emetic vagal afferents are capsaicin-sensitive C fibers which may have substance P as an excitatory transmitter or modulator.

Animals↗

The internal organization of the human solitary nucleus.

The present study examines the topography and cytoarchitecture of the solitary nucleus (Sol). Three human medulla oblongatae were serially sectioned and alternate sections were reacted for the enzyme acetylcholinesterase or stained with cresyl violet. The 10 component subnuclei of Sol were identified on the basis of their acetylcholinesterase reactivity and cytoarchitecture. These subnuclei are the paracommissural, commissural, gelatinosus, medial, ventral, ventrolateral, dorsal, dorsolateral, intermediate, and interstitial. Cytoarchitecturally, Sol is characterised by an abundance of small cells of varied morphology but also features some medium to large cells as well as pigmented neurons which are differentially distributed across the subnuclei. From spaced serial sections, the outlines of the subnuclei and the entire Sol were used to create three-dimensional computer reconstructions to display the position and extent of each component subnucleus. Our results show that the internal architecture of the human solitary nucleus is similar to that of rodents and carnivores, though there are some notable species differences.

Acetylcholinesterase↗

Morphological types of neurons located at taste-responsive sites in the solitary nucleus of the hamster.

HRP histochemistry and microelectrode mapping were combined to study the sizes, shapes, and orientations of neuronal cell bodies and dendrites located at sites of taste-elicited single unit activity in the nucleus of the solitary tract (NST). Cells responding to sapid stimulation of the anterior tongue were extracellularly recorded using micropipettes containing HRP. Iontophoretic injection of the marker at the recording sites resulted in small (50-200 microns diameter) opaque zones bordered by a small number (2-15) of neurons with Golgi-like filling of their cell bodies, dendrites, and to some extent, their axons. The cell bodies were near (50-250 microns) the injection sites into which they sent labelled dendrites. Two broad categories of neurons were typically filled. Elongate cells had oval- to spindle-shaped cell bodies oriented mediolaterally. Two primary dendrites extended 100-300 microns from the cell body, one medially and one laterally, and branched within a cylindrical dendritic field oriented mediolaterally. A minority of the HRP-filled elongate cells had unusually long rostrally or caudally directed dendritic branches. Stellate cells had oval, round, triangular, or polygonal cell bodies and 3-5 primary dendrites coursing 200-300 microns in all directions and branching as unoriented, spheroidal fields. A minority of stellate cells had relatively unbranched wavy dendrites, resembling tentacles, while others had unusually small cell bodies (10-15 microns diameter), small dendrites, and locally arborizing axons. Of 151 labelled cells, all but 12 were remarkably confined to the rostral NST. Nearly 90% were concentrated in the rostral central cytoarchitectonic subdivision, where stellate cells predominated, or in the rostral lateral subdivision, where elongate cells predominated. These morphological types of neurons, filled at neurophysiological recording sites, are compared with cell types identified in previous light and electron microscopic studies of the cytoarchitecture, connections, and synaptic organization of the gustatory NST.

Animals↗

Alpha-1 adrenergic input to solitary nucleus neurones: calcium oscillations, excitation and gastric reflex control.

The nucleus of the solitary tract (NST) processes substantial visceral afferent input and sends divergent projections to a wide array of CNS targets. The NST is essential to the maintenance of behavioural and autonomic homeostasis and is the source, as well as the recipient, of considerable noradrenergic (NE) projections. The significance of NE projections from the NST to other CNS regions has long been appreciated, but the nature of NE action on NST neurones themselves, especially on the alpha-1 receptor subtype, is controversial. We used a combination of methodologies to establish, systematically, the effects and cellular basis of action of the alpha-1 agonist, phenylephrine (PHE), to control NST neurones responsible for vago-vagal reflex regulation of the stomach. Immunocytochemical and retrograde tracing studies verified that the area postrema, A2, A5, ventrolateral medulla and locus coeruleus regions are sources of catecholaminergic input to the NST. In vivo electrophysiological recordings showed that PHE activates physiologically identified, second-order gastric sensory NST neurones. In vivo microinjection of PHE onto NST neurones caused a significant reduction in gastric tone. Finally, in vitro calcium imaging studies revealed that PHE caused dramatic cytosolic calcium oscillations in NST neurones. These oscillations are probably the result of an interplay between agonist-induced and inositol 1,4,5-trisphosphate (IP(3))-mediated intracellular calcium release and Ca(2+)-ATPase control of intracellular calcium storage pumps. The oscillations persisted even in perfusions of zero calcium-EGTA Krebs solution suggesting that the calcium oscillation is mediated principally by intracellular calcium release-reuptake mechanisms. Cyclical activation of the NST may function to increase the responsiveness of these neurones to incoming afferent input (i.e., elevate the "gain"). An increase in gain of afferent input may cause an amplification of the response part of the reflex and help explain the powerful effects that alpha-1 agonists have in suppressing gastric motility and producing anorexia.

Adrenergic alpha-Agonists↗

TNF-alpha activates solitary nucleus neurons responsive to gastric distension.

Tumor necrosis factor-alpha (TNF-alpha) is liberated as part of the immune response to antigenic challenge, carcinogenesis, and radiation therapy. Previous studies have implicated elevated circulating levels of this cytokine in the gastric hypomotility associated with these disease states. Our earlier studies suggest that a site of action of TNF-alpha may be within the medullary dorsal vagal complex. In this study, we describe the role of TNF-alpha as a neuromodulator affecting neurons in the nucleus of the solitary tract that are involved in vago-vagal reflex control of gastric motility. The results presented herein suggest that TNF-alpha may induce a persistent gastric stasis by functioning as a hormone that modulates intrinsic vago-vagal reflex pathways during illness.

Animals↗

Evidence for alpha-2 adrenoreceptor modulation of arterial chemoreflexes in the caudal solitary nucleus of the rat.

The caudal region of the nucleus of the solitary tract (cNTS) is the primary central termination site for arterial chemoreceptor afferents originating from the carotid body. The purpose of the present study was to investigate the role of endogenous activation of alpha-2 adrenoreceptors in the cNTS on arterial chemoreflex function. Arterial chemoreflex responses to intravenous injections of potassium cyanide (KCN; 75 microg/kg) were recorded before and following blockade of alpha-2 adrenoreceptors in the cNTS of urethane-anesthetized rats. KCN alone elicited a reflex increase in arterial pressure, renal sympathetic nerve activity, and respiration. After bilateral cNTS microinjection of alpha-2 receptor antagonists (2 nmol idazoxan or 0.2 nmol yohimbine), arterial chemoreflex responses were markedly attenuated. Attenuation of chemoreflex function was not accompanied by any significant change in resting blood pressure or respiratory rate. The results suggest that the endogenous activation of alpha-2 adrenoreceptors facilitates central processing of chemoreceptor afferent inputs in the cNTS of the rat.

Adrenergic alpha-2 Receptor Antagonists↗

Taste responses of neurons of the hamster solitary nucleus are enhanced by lateral hypothalamic stimulation.

Gustatory responses in the brain stem are modifiable by several physiological factors, including blood insulin and glucose, intraduodenal lipids, gastric distension, and learning, although the neural substrates for these modulatory effects are not known. Stimulation of the lateral hypothalamus (LH) produces increases in food intake and alterations in taste preference behavior, whereas damage to this area has opposite effects. In the present study, we investigated the effects of LH stimulation on the neural activity of taste-responsive cells in the nucleus of the solitary tract (NST) of the hamster. Bipolar stimulating electrodes were bilaterally implanted in the LH, and the responses of 99 neurons in the NST, which were first characterized for their taste sensitivities, were tested for their response to both ipsilateral and contralateral LH stimulation. Half of the taste-responsive cells in the NST (49/99) were modulated by LH stimulation. Contralateral stimulation was more often effective (41 cells) than ipsilateral (13 cells) and always excitatory; 10 cells were excited bilaterally. Six cells were inhibited by ipsilateral stimulation. A subset of these cells (n = 13) was examined for the effects of microinjection of DL-homocysteic acid (DLH), a glutamate receptor agonist, into the LH. The effects of electrical stimulation were completely mimicked by DLH, indicating that cell somata in and around the LH are responsible for these effects. Other cells (n = 14) were tested for the effects of electrical stimulation of the LH on the responses to stimulation of the tongue with 0.032 M sucrose, NaCl, and quinine hydrochloride, and 0.0032 M citric acid. Responses to taste stimuli were more than doubled by the excitatory influence of the LH. These data show that the LH, in addition to its role in feeding and metabolism, exerts descending control over the processing of gustatory information through the brain stem.

Animals↗

Amiloride blocks acid responses in NaCl-best gustatory neurons of the hamster solitary nucleus.

Biophysical studies of isolated taste receptor cells show that one mechanism of Na+ salt transduction involves the inward movement of Na+ through amiloride-blockable ion channels on the apical receptor cell membrane, which leads to a direct depolarization. Hamster taste receptor cells with amiloride-blockable Na+ responses also show an amiloride-sensitive H+ current. Thus one mechanism for the transduction of acid taste involves the amiloride-sensitive channel. We investigated the effects of amiloride on responses to acids in neurons of the nucleus of the solitary tract (NST) of the hamster. The responses of 47 NST neurons were recorded extracellularly while the anterior tongue was stimulated with solutions representing the four taste qualities (NaCl, sucrose, HCl, quinine), which were used to characterize each cell on the basis of its best stimulus. The effects of amiloride on responses to 10 mM HCl, 10 mM citric acid, 100 mM NaCl, and 100 mM sucrose were then investigated. Stimuli were presented alone for 30 s (control trials) and also presented for 10 s, followed by a mixture of the stimulus with 10 microM amiloride for 10 s, followed by the stimulus alone again for 10 s (amiloride trials). The effects of amiloride were assessed by comparing the responses of cells with the stimulus + amiloride with that of the stimulus alone. In neurons classified as NaCl-best, amiloride reversibly blocked responses to NaCl, HCl, and citric acid. In HCl-best neurons, amiloride had no effect on responses to any of these stimuli. In sucrose-best neurons, amiloride blocked the response to NaCl but not to sucrose or to either acid. These results support the hypothesis that acids are transduced by at least two different receptor mechanisms in the hamster, amiloride sensitive and amiloride insensitive. At the NST, these inputs are tightly maintained in two separate populations of neurons. Sucrose-best neurons, which show amiloride effects on NaCl but not acids, appear to receive converging inputs from both amiloride-sensitive (N-best) and amiloride-insensitive (H-best) chorda tympani nerve fibers.

Action Potentials↗

Neural representation of the taste of NaCl and KCl in gustatory neurons of the hamster solitary nucleus.

NaCl and KCl are monovalent salts that can be discriminated behaviorally by hamsters on the basis of their tastes. We examined the effects of the passive Na+ channel blocker amiloride on responses to both of these salts in 34 taste-responsive neurons of the nucleus of the solitary tract (NST) in the hamster. The effects of amiloride were assessed with two different, commonly employed stimulus protocols. Additionally, concentration-response functions for each salt were measured in 37 neurons. Cells were characterized by their best response to (in M) 0. 03 NaCl, 0.1 sucrose, 0.003 HCl, 0.001 quinine hydrochloride, and 0. 1 KCl. In neurons classified as NaCl-best, amiloride reversibly blocked responses to both NaCl and KCl. In neurons classified as HCl-best, amiloride had no effect on either stimulus. In sucrose-best neurons, amiloride blocked the response to NaCl but not KCl. These results support the hypothesis that both salts are transduced by at least two different receptor mechanisms. In the NST, information arising from these different inputs is maintained in discrete populations of neurons. In addition to differences in amiloride sensitivity, the cell types also differed in their responses to the salts across concentration. At midrange salt concentrations, NaCl-best neurons were far more responsive to NaCl than KCl, whereas HCl- and sucrose-best neurons responded equivalently to the two salts at all concentrations. Because NaCl- and HCl-best cells cannot by themselves distinguish NaCl from KCl, it is the relative activity across these cell types that comprises the code for taste discrimination.

Action Potentials↗

Neural representation of salts in the rat solitary nucleus: brain stem correlates of taste discrimination.

One mechanism of salt taste transduction by gustatory receptor cells involves the influx of cations through epithelial sodium channels that can be blocked by oral application of amiloride. A second mechanism is less clearly defined but seems to depend on electroneutral diffusion of the salt through the tight junctions between receptor cells; this paracellular pathway is insensitive to amiloride. Because the first mechanism is more sensitive to sodium salts and the second to nonsodium salts, these peripheral events could underlie the ability of rats to discriminate sodium from nonsodium salts on the basis of taste. Behavioral experiments indicate that amiloride, at concentrations that are tasteless to rats, impairs a rat's ability to discriminate NaCl from KCl and may do so by making both salts taste like KCl. In the present study, we examined the neural representation of NaCl and KCl (0.05-0.2 M), and mixtures of these salts with amiloride (0, 3, and 30 microM), to explore the neural correlates of this behavioral result. NaCl and KCl were represented by distinct patterns of activity in the nucleus of the solitary tract. Amiloride, in a concentration-dependent manner, changed the pattern for NaCl to one more characteristic of KCl, primarily by reducing activity in neurons responding best to NaCl and sucrose. The effect of amiloride concentration on the response to 0.1 M NaCl in NaCl-best neurons was virtually identical to its effect on behavioral discrimination performance. Modeling the effects of blocking the amiloride-insensitive pathway also resulted in highly similar patterns of activity for NaCl and KCl. These results suggest that activity in both the amiloride-sensitive and -insensitive pathways is required for the behavioral discrimination between NaCl and KCl. In the context of published behavioral data, the present results suggest that amiloride-sensitive activity alone is not sufficient to impart a unique signal for the taste of sodium salts.

Action Potentials↗

Taste responses of neurons in the hamster solitary nucleus are modulated by the central nucleus of the amygdala.

Previous studies have shown a modulatory influence of forebrain gustatory areas, such as the gustatory cortex and lateral hypothalamus, on the activity of taste-responsive cells in the nucleus of the solitary tract (NST). The central nucleus of the amygdala (CeA), which receives gustatory afferent information, also exerts descending control over taste neurons in the parabrachial nuclei (PbN) of the pons. The present studies were designed to investigate the role of descending amgydaloid projections to the NST in the modulation of gustatory activity. Extracellular action potentials were recorded from 109 taste-responsive cells in the NST of urethan-anesthetized hamsters and analyzed for a change in excitability following electrical and chemical stimulation of the CeA. Electrical stimulation of the CeA orthodromically modulated 36 of 109 (33.0%) taste-responsive NST cells. An excitatory response was observed in 33 (30.28%) cells. An initial decrease in excitability to electrical stimulation of the CeA, suggestive of postsynaptic inhibition, was observed in three (2.75%) NST taste cells. NST cells modulated by the CeA were significantly less responsive to taste stimuli than cells that were not. Many of these cells were under the modulatory influence of the contralateral CeA (28/36 = 77.8%) as well as the ipsilateral (22/36 = 61.1%); 14 (38.9%) were excited bilaterally. Latencies for excitation were longer after ipsilateral than after contralateral CeA stimulation. Microinjection of DL-homocysteic acid (DLH) into the CeA mimicked the effect of electrical stimulation on each of the nine cells tested: DLH excited eight and inhibited one of these electrically activated NST cells. Application of subthreshold electrical stimulation to the CeA during taste trials increased the taste responses of every CeA-responsive NST cell (n = 7) tested with this protocol. These effects would enhance taste discriminability by increasing the signal-to-noise ratio of taste-evoked activity.

Amygdala↗

Intramedullary connections of the gastric region in the solitary nucleus: a biocytin histochemical tracing study in the rat.

The local circuit neurons in the solitary nucleus that form part of a gastro-gastric vago-vagal reflex were examined using a biocytin/avidin-peroxidase histochemical tracing method in the male Long-Evans rat. Iontophoretic deposits of very small amounts of biocytin were made into the ventral commissural nucleus of the solitary tract (vcNTS) where the excitatory neuronal response to antral distension was recorded. The tracing study revealed substantial axonal projections from the vcNTS to the immediately subjacent dorsal motor nucleus of the vagus (DMN) as well as the parvocellular reticular formation (pcRF). Some axons also appeared to terminate on neurons of the nucleus retroambiguus (nRAm) in the same coronal plane as the injection site. Labeled NTS neurons in the immediate area of the injection site revealed a clear horizontally-oriented pattern of dendrites, some of which extended from the midline to the solitary tract. Some of these dendrites could be found within the walls of arterioles, the central canal or in the area postrema. This finding suggests that vcNTS neurons activated by antral inflation are probably influenced by a number of other neural and chemical afferent signals.

Animals↗

Spinal and vagal influences on the responses of rat solitary nucleus neurons to stimulation of uterus, cervix and vagina.

Neurons in the rat solitary nucleus (NTS) respond to mechanical stimulation of the uterine horn, cervix and vagina. The present study examined how these responses were affected by bilateral vagotomy and/or T10-T12 spinal transection for 12 single NTS neurons recorded in 12 rats anesthetized with halothane/nitrous oxide. Spinal transections all responses. Vagotomies eliminated responses only to uterine horn stimulation and either reduced the excitatory or enhanced the inhibitory responses to cervix and vaginal stimuli. These results suggest that NTS neuronal responses to cervix and vaginal stimulation depend upon input from the spinal dorsal horn and are facilitated by vagal input, whereas responses to uterine horn stimulation may require both spinal and vagal input.

Animals↗

Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex.

Activation of esophageal mechanosensors excites neurons in and near the central nucleus of the solitary tract (NSTc). In turn, NSTc neurons coordinate the relaxation of the stomach [i.e., the receptive relaxation reflex (RRR)] by modulating the output of vagal efferent neurons of the dorsal motor nucleus of the vagus (DMN). The NSTc area contains neurons with diverse neurochemical phenotypes, including a large population of catecholaminergic and nitrergic neurons. The aim of the present study was to determine whether either one of these prominent neuronal phenotypes was involved in the RRR. Immunohistochemical techniques revealed that repetitive esophageal distension caused 53% of tyrosine hydroxylase-immunoreactive (TH-ir) neurons to colocalize c-Fos in the NSTc. No nitric oxide synthase (NOS)-ir neurons in the NSTc colocalized c-Fos in either distension or control conditions. Local brain stem application (2 ng) of alpha-adrenoreceptor antagonists (i.e., alpha1-prazosin or alpha2-yohimbine) significantly reduced the magnitude of the esophageal distension-induced gastric relaxation to approximately 55% of control conditions. The combination of yohimbine and prazosin reduced the magnitude of the reflex to approximately 27% of control. In contrast, pretreatment with either the NOS-inhibitor NG-nitro-l-arginine methyl ester or the beta-adrenoceptor antagonist propranolol did not interfere with esophageal distension-induced gastric relaxation. Unilateral microinjections of the agonist norepinephrine (0.3 ng) directed at the DMN were sufficient to mimic the transient esophageal-gastric reflex. Our data suggest that noradrenergic, but not nitrergic, neurons of the NSTc play a prominent role in the modulation of the RRR through action on alpha1- and alpha2-adrenoreceptors. The finding that esophageal afferent stimulation alone is not sufficient to activate NOS-positive neurons in the NSTc suggests that these neurons may be strongly gated by other central nervous system inputs, perhaps related to the coordination of swallowing or emesis with respiration.

Adrenergic Agonists↗