Vagal Afferent Input Research Articles

Role of glutamate receptors in transmission of vagal cardiac input to neurones in the nucleus tractus solitarii in dogs.

1. Vagal afferent input from cardiac mechanoreceptors excites neurones in the nucleus tractus solitarii (NTS), but discharge patterns evoked by physiological activation of pressure-sensitive cardiac mechanoreceptors have not been studied in vivo. The role of glutamate receptor subtypes in transmission of afferent activity to the NTS neurones has not been determined. The present study therefore has two aims: first, to characterise the discharge patterns of neurones in the NTS that receive pressure-sensitive vagal cardiac receptor input and second, to determine the roles of ionotropic glutamate receptor subtypes in the transmission of this putative cardiac mechanoreceptor-related activity to NTS neurones. 2. Pulse-synchronous activity of neurones in the NTS evoked by vagal afferent input was recorded extracellularly in an anaesthetised dog model using multibarrel glass electrodes, which allowed picoejection of the glutamate receptor antagonists NBQX or AP5 to block either non-NMDA or NMDA receptors, respectively, during the neuronal recording. Pressure sensitivity of the recorded neurones was examined by monitoring their response to a small increase in arterial blood pressure. Selective pressure activation of carotid sinus baroreceptors in an isolated sinus or selective denervation of aortic baroreceptors were used to test for convergent excitation of the neurones by arterial baroreceptors. 3. Pulse-synchronous cardiac-related neuronal activity recorded from neurones in both the right and left NTS was eliminated following section of the left (n = 17) or right (n = 1) vagus nerves. No spontaneous, non-pulsatile activity was observed in these neurones before or after vagotomy. Activity transmitted via left vagal afferents was found to be sensitive to changes in arterial blood pressure. In these neurones, activity was blocked in 13 of 17 neurones by picoejection of NBQX, with the remainder requiring both NBQX and AP5. None of the cardiac-related neurones responded to activation of carotid baroreceptors or denervation of aortic baroreceptors, indicating no convergence of activity from carotid baroreceptors or aortic baroreceptors with pressure thresholds of approximately 130 mmHg or less. 4. The results suggest that vagal pressure-sensitive afferent input from cardiac mechanoreceptors is transmitted primarily by left vagal afferent fibres via non-NMDA receptors to neurones in both the ipsilateral and contralateral NTS. NMDA receptors were also found to have a role in the activation of a small subpopulation of neurones.

Sympathetic responses to cardiopulmonary vagal afferent stimulation during development.

Previous work in our laboratory has demonstrated impairment of cardiopulmonary reflex control of renal sympathetic nerve activity (RSNA) during the newborn period. The present study was designed to test the hypothesis that this delayed maturation is secondary to incomplete central integration of vagal afferent input. Term fetal (135-140 days; n = 6), newborn (3-7 days of age; n = 8), and young adult (6-8 wk old; n = 8) sheep anesthetized with alpha-chloralose underwent vagal afferent nerve stimulation. All animals had undergone prior sinoaortic denervation to eliminate influences from the arterial baroreceptors. After determination of optimal stimulation parameters, RSNA responses to gradual increases in stimulation frequency (1.0-16 Hz) were recorded and compared by one-way ANOVA. RSNA decreased progressively with increased frequency of stimulation in all three groups of animals. When comparing the three groups at any given frequency of stimulation, reflex withdrawal of RSNA tended to be more pronounced in newborn lambs (P < 0.05 for 1 and 4 Hz). Heart rate (HR) was also noted to decrease significantly with vagal afferent stimulation in each of the groups, but no significant differences in the reflex decreases in HR were noted among the three groups of animals. These results demonstrate that central integration of vagal afferent input is intact in fetal and newborn sheep. These results suggest that the delayed maturation of cardiopulmonary reflex-mediated changes in RSNA seen early in development appears to depend on intrinsic alterations in baroreceptor function rather than incomplete central integration.

Activation of ascending antinociceptive system by vagal afferent input as revealed in the nucleus ventralis posteromedialis

Thalamic nociceptive neurons receiving afferent input from the tooth pulp (TP) were recorded from the nucleus ventralis posteromedialis proper (VPM) in cats anesthetized with urethane and chloralose. Effects of cervical vagus nerve stimulation on responses of TP neurons in the VPM were investigated. Twenty-one tooth pulp specific (TPS) and eight wide dynamic range (WDR) neurons with TP input were obtained from the periphery (shell region) of the posterior half of the VPM. Of these, many were also excited by electrical stimulation of trigeminothalamic tract (TTT) fibers in the trigeminal medial lemniscus. A conditioning-test paradigm was used to examine effects of vagal stimulation on responses of VPM neurons to electrical stimulation of TP and TTT. Inhibition of the responses was observed in 12 TPS and seven WDR neurons. Local anesthetic block of the mesencephalic periaqueductal gray (PAG) and/or nucleus raphe dorsalis (NRD) eliminated the inhibitory effects of vagal stimulation on the responses of both classes of TP neurons to TTT stimulation. In contrast, the inhibitory effects on responses to TP stimulation were insignificantly affected. These data suggest that vagal afferents can activate the ascending antinociceptive pathway from PAG/NRD onto VPM, in addition to activating the descending antinociceptive system acting upon the lower brain stem.

Interaction between somatic and vagal afferent inputs in control of ventilation in 2-week-old rabbits

Effects of saphenous nerve stimulation (SNS) on the Hering–Breuer expiratory-promoting reflex evoked by a positive tracheal pressure (P tr; 5 cmH 2O) and on the diaphragmatic EMG (EMG di), inspiratory (T i) and expiratory (T e) time, were studied in 16 urethane-anesthetized (1.2–1.6 g/kg, i.p.) spontaneously breathing 2-week-old rabbits. Positive P tr applied at the end of T i increased the subsequent T e to 255±29% (±S.E.; P<0.0001) of control. SNS (1 sec train, 2 msec pulse, 6 Hz) applied at the onset of T e, shortened this T e by 42±3% ( P<0.0001). When SNS preceded positive P tr or positive P tr preceded SNS, the T e increased to 163±20 and 184±21% of control, respectively. These responses were not different, and smaller than that provoked by the P tr test alone ( P<0.003 and 0.05, respectively). The results show that in newborns somatic afferent stimulation attenuates the vagally mediated respiratory inhibition, whether immediately before or during the vagal stimulation.

Vagal modulation of responses elicited by stimulation of the aortic depressor nerve in neurons of the rostral ventrolateral medulla oblongata in the rat

Stimulation of cervical vagal afferents inhibits central sympathetic outflows in part by inhibiting the ongoing activity of putative baroreceptive neurons in the rostral ventrolateral medulla oblongata. The aim of the present study was to examine the electrophysiological characteristics of vagal responses and their interactions with responses elicited by stimulation of the aortic nerve in neurons there. The study focused on the role of the long-lasting, late-onset vagal inhibition, which is likely to play an important role in the tonic inhibitory effects of vagal afferent stimulation. In vivo intracellular recordings were obtained from 33 neurons that received convergent inputs from aortic and vagal afferents. Sixty-four percent of these neurons exhibited a late inhibition following electrical stimulation of myelinated vagal afferents (mean onset latency of 100±5 ms). The average duration of late inhibition (294±19 ms) exceeded the duration of the cardiac cycle. As a consequence of this, sustained vagal stimulation diminished the effect of rhythmic baroreceptor inputs in neurons that exhibited late vagal inhibition. Simultaneous activation of aortic and vagal afferents significantly increased the magnitude of late inhibition, even in those neurons where stimulation of the aortic nerve alone did not elicit a response ( n=15). This suggested that the convergence between vagal and aortic afferent inputs occurred in inhibitory interneurons antecedent to the recorded rostral ventrolateral medulla oblongata neurons. Focal stimulation of the caudal part of the nucleus of the solitary tract also elicited a late-onset inhibition in 73% of the neurons that responded to stimulation of the aortic nerve. This inhibition appeared to be similar to the late vagal inhibition, except for its shorter average onset latency (64±7 ms). Based on this observation, it is proposed that inhibitory interneurons that mediate late inhibition to rostral ventrolateral medulla oblongata neurons may lie within the caudal part of the nucleus of the solitary tract. The present study established that activation of myelinated vagal afferents exerts a complex modulation over the ongoing and evoked activity of neurons that respond to stimulation of the aortic nerve. The complex interaction that occurs between aortic and vagal inputs in neurons of the rostral ventrolateral medulla may be implicated in long-term modulation of sympathetic outflows in response to changes in the activation of visceral receptors supplied by vagus afferents. The modulation elicited by late vagal inhibition may help to adjust cardiovascular outflows according to requirements set by the thoraco-abdominal visceral environment.

Reflex inhibition of canine inspiratory intercostals by diaphragmatic tension receptors.

1. Electrical stimulation of phrenic afferent fibres in the dog elicits a reflex inhibition of efferent activity to the inspiratory intercostal muscles. However, electrical stimulation has a poor selectivity, so the sensory receptors responsible for this inhibition were not identified. 2. In the present studies, cranial forces were applied during spontaneous inspiration to the abdominal surface of the central, tendinous portion of the canine diaphragm to activate tension mechanoreceptors in the muscle. Vagal afferent inputs were eliminated by vagotomy. 3. The application of force to the central tendon caused a graded, reflex reduction in inspiratory intercostal activity, especially in external intercostal activity. This reduction was commonly associated with a decrease in inspiratory duration and was invariably attenuated after section of the cervical dorsal roots. 4. In contrast, no change in inspiratory intercostal activity was seen when high frequency mechanical vibration was applied to the central tendon to stimulate diaphragmatic muscle spindles. 5. These observations provide strong evidence that tension receptors in the diaphragm, but not muscle spindles, induce reflex inhibition of inspiratory intercostal activity. The expression of this reflex probably involves supraspinal structures.

A biofeedback system of baroreceptor cardiac reflex sensitivity.

The evidence presently available suggests that the parasympathetic nervous system and sympathetic-parasympathetic interactions could play a role in the pathophysiology of cardiovascular disorders and, specifically, in hypertension. A loss of sensitivity of the baroreceptor reflex is one of the fundamental mechanisms underlying the deficits found in parasympathetic cardiac control. The baroreceptor reflex is a basic mechanism for the regulation of blood pressure, a powerful source of vagal afferent input to the central nervous system, and one of the most important physiological mechanisms affecting efferent cardiac vagal activity. This paper describes a computerized system for the on-line analysis of the baroreceptor cardiac reflex function using the noninvasive spontaneous sequence method in the time domain. The system provides feedback of the baroreceptor reflex sensitivity (the change in heart period per unit change in systolic blood pressure) differentially both when the systolic blood pressure is increasing and when it is decreasing. The accuracy of the described system has been tested against the conventional off-line procedure. None of the parameters supplied by the analysis show a significant difference between the on-line and off-line methods. These results confirm the accuracy of the on-line system to analyze baroreceptor cardiac reflex function.

Brainstem pathways responsible for oesophageal control of gastric motility and tone in the rat.

1. Previous anatomical studies indicate that the nucleus of the solitary tract, pars centralis (NSTc) contains the neurones which receive vagal afferent input from the oesophagus. The purpose of the present study was to characterize the NSTc circuits in the medulla that may be responsible for oesophageal control of gastric motility. 2. Moderate balloon distension of the oesophagus of the rat (14-18 mmHg) provoked a significant reduction in gastric motility and tone recorded with strain gauges. This receptive relaxation effect was eliminated by bilateral lesions centred on the NSTc. 3. NSTc cells activated by oesophageal distension were labelled extracellularly and juxtacellularly with neurobiotin. NSTc neurones send axonal projections throughout the entire rostral-caudal extent of the dorsal motor nucleus of the vagus (DMN). These NSTc-DMN connections were confirmed by retrograde transport of neurobiotin from DMN to NSTc. NSTc neurones were observed with dendrites arborizing within the ependymal lining of the fourth ventricles. Thus, NSTc neurones may be in position to monitor blood-borne or ventricular agents and to alter the function of gastric-vago-vagal reflexes in response to these stimuli. 4. Neurophysiological recordings identified two subpopulations of DMN neurones which may be either activated or inhibited by oesophageal distension. Neurones excited by oesophageal distension were located mainly lateral and caudal in the DMN; neurones inhibited by oesophageal stimulation were located in medial and rostral DMN. 5. Our neurobiotin tracing results verified earlier studies showing that the NSTc projects to the intermediate reticular nucleus and the compact division of the nucleus ambiguus. Additionally, we found that the NSTc may be involved in reciprocal connections with the anterior, rostrolateral NST. 6. These results suggest that the gastric relaxation evoked by oesophageal distension is critically dependent on intact brainstem vago-vagal circuits. The NSTc, the recipient of oesophageal afferent projections from the vagus nerve, sends axons to the entire DMN, the source of parasympathetic control of the stomach. DMN neurones respond differentially to oesophageal distension, reinforcing the view that oesophageal afferents may provoke gastric relaxation by activating a vagal inhibitory pathway while simultaneously inhibiting a vagal excitatory pathway.

Suppressive effect of vagal afferents on the activity of the trigeminal spinal neurons related to the jaw-opening reflex in rats: involvement of the endogenous opioid system

The purpose of the present study is to test the hypothesis that via the endogenous pain control system, vagal afferent input modulates the activity of the trigeminal spinal nucleus oralis (TSNO) related to the tooth pulp (TP)-evoked jaw-opening reflex (JOR). Extracellular single-unit recordings were made from 36 TSNO units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram (dEMG) signal in 26 pentobarbital-anesthetized rats. The activity of 36 TSNO neurons and the amplitude of the dEMG increased proportionally during 1.0–3.5 times the threshold for JOR. Some of these neurons (4 out of 5) were also excited by chemical stimulation (bradykinin, 1–2 μl, 1 mM) of TP. In 31 out of 36 TSNO neurons (86%), their activities during tooth pulp stimulation were suppressed by conditioning stimulation of the right vagus nerve. The suppressive effect of vagal afferent stimulation occurred at conditioning-test intervals of 20–150 ms after the onset of the stimulation, and its maximal suppressive effect occurred at approximately 50 ms. The mean time course of this suppressive effect paralleled that of the dEMG. After administration of naloxone (0.5 and 1.0 mg/kg, i.v.), an opiate receptor blocker, the suppressive effect on the activity of TSNO neurons (6 out of 8) was significantly attenuated at the conditioning-test interval of 50 ms compared to the control ( p < 0.01). These results suggested that vagal afferent input inhibits nociceptive transmission in the TSNO related to TP-evoked JOR and this inhibitory effect may occur via the endogenous opioid system in rats.

The distribution of nitric oxide synthase-, adenosine deaminase- and neuropeptide Y-immunoreactivity through the entire rat nucleus tractus solitarius: Effect of unilateral nodose ganglionectomy

The present study has employed immunocytochemistry on free-floating sections of adult rat medulla oblongata to characterise the distribution of nitric oxide synthase- (NOS), adenosine deaminase- (ADA) and neuropeptide Y- (NPY) immunoreactivity (IR) throughout the entire rostro–caudal axis of the nucleus tractus solitarius (NTS). In addition, unilateral nodose ganglionectomy was performed in a group of rats to determine whether any observed immunoreactivity was associated with central vagal afferent terminals. NOS-IR was found throughout the entire NTS, in cells, and both varicose and non-varicose fibres. Furthermore, unilateral nodose ganglionectomy resulted in a clear reduction in NOS-IR (visualised with diaminobenzidine) in a highly restricted portion of the ipsilateral medial NTS. Similarly, ADA- and NPY-containing cells, fibres and terminals were also found throughout the adult rat NTS. However, following unilateral nodose ganglionectomy, there was no apparent reduction in either ADA-IR or NPY-IR on the denervated side of the NTS. These data indicate a role for nitric oxide, purines and neuropeptide Y as neuromodulators within the rat NTS, although only nitric oxide appears to be primarily associated with vagal afferent input. Adenosine deaminase and neuropeptide Y-containing neurons appear to be predominantly postsynaptic to vagal input, although their possible association with vagal afferents cannot be completely excluded.

Importance of neurokinin-1 receptors in the nucleus tractus solitarii of mice for the integration of cardiac vagal inputs.

Unmyelinated vagal afferents from the heart terminate within the nucleus tractus solitarii (NTS) located in the dorsomedial medulla. The neurotransmitter and postsynaptic receptors mediating information from cardiac vagal receptors to the NTS are unknown. This study determined the effects of neurokinin-1 (NK1) receptor blockade on: (i) the reflex response evoked following aortic root injection of either veratridine (1-3 microg/kg) or bradykinin (80-300 ng/kg) to stimulate cardiac receptors in in vivo anaesthetized mice; and (ii) the evoked synaptic response of cardioreceptive NTS neurons following both intraleft-ventricular injection of veratridine or bradykinin, and electrical stimulation of the ipsilateral vagus nerve in an arterially perfused working heart-brainstem preparation of mouse. Administration of CP-99,994 (0.75-1.5 mg/kg i.v.), a specific NK1 antagonist, attenuated significantly the evoked reflex bradycardia and depressor response following cardiac receptor (n = 6), but not pulmonary chemoreflex stimulation in vivo. From extracellular recordings of cardioreceptive NTS neurons, CP-99,994 reduced reversibly the total number of evoked spikes, peak firing frequency and response duration evoked by intraventricular injections of veratridine (n = 5) or bradykinin (n = 5). The number of evoked action potentials following electrical stimulation of the vagus nerve was also reduced. In five whole cell recordings of NTS neurons, both the evoked depolarization following cardiac receptor stimulation, and the peak amplitude and duration of vagus nerve-evoked EPSPs were reduced by CP-99,994; synaptic inputs from both peripheral chemoreceptors or pulmonary C-fibres were unaffected. These data support a selective involvement of NK1 receptors in the transmission of cardiac vagal afferent inputs to NTS neurons integrating cardiorespiratory information.

Interactions between sympathetic and vagal cardiac afferents in nucleus tractus solitarii.

Epicardial application of hydrogen peroxide (H2O2) reflexly elicits a sympathetically mediated pressor response. This pressor response is augmented by vagotomy and abolished by sympathectomy, suggesting an occlusive interaction between the afferents in the central nervous system (CNS). To support this observation we recorded sympathetic efferent responses from the sympathetic chain (T1-T2) before and after epicardial application of H2O2 in six cats before and after vagotomy. Cardiac sympathetic efferent responses to H2O2 were increased by vagotomy. Thus there exists an occlusive interaction between the two afferent pathways in the CNS. Because cardiopulmonary vagal afferents make their first central synapse in the nucleus tractus solitarii (NTS), we further hypothesized that cells in the NTS receive convergent inputs from sympathetic and vagal afferents and that the inputs would interact in an occlusive manner. In alpha-chloralose-anesthetized sinoaortic-denervated cats, cardiac sympathetic and vagal branches were stimulated electrically at 1 Hz, either separately or in combination. Extracellular single-unit activity was recorded in the NTS. Vagal stimuli most frequently (38%) diminished sympathetically evoked unit activity (-46.6 +/- 6.0%) versus control (1.4 +/- 1.5%). However, a few (21%) vagal and sympathetic afferent inputs were found to be additive or facilitative. We conclude that interactions occur between cardiac sympathetic and vagal afferents in the NTS. It is possible that this occlusive interaction explains the alteration in cardiac sympathetic outflow after epicardial stimulation with H2O2.

In Vivo Effects of 5-Hydroxytryptamine Receptor Activation on Rat Nucleus Tractus Solitarius Neurones Excited by Vagal C-fibre Afferents

The effects of ionophoretically applied 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists were studied on rat nucleus tractus solitarius (NTS) neurones receiving unmyelinated vagal afferent input. 5-HT excited 15 of 34 neurones (44%), inhibited 10 (29%) and had no effect on nine. 8-Hydroxy-2-(di-N-propylamino)tetralin HBr (8-OH-DPAT) excited 23 of 53 neurones (43%), inhibited 24 (45%) and had no effect on six neurones and (±)-2,5-dimethoxy-4-iodoamphetamine HCl activated 18 of 37 neurones (49%), inhibited nine (24%) and had no effect on 10. These results demonstrate that activation of 5-HT1A and 5-HT2 receptors can excite or inhibit populations of NTS neurones. Phenylbiguanide, however, excited 20 of 23 neurones (87%), inhibited only one (4%) and had no effect on two indicating that 5-HT3 receptor activation has an excitatory action. NTS neurones receiving cardiac vagal afferent input were more likely to be excited by 5-HT (five of five, 100%) or 8-OH-DPAT (four of five, 80%) than the population as a whole. In conclusion, the data demonstrate that 5-HT1A, 5-HT2, and 5-HT3 receptor subtypes are functionally present on NTS neurones receiving excitatory vagal afferent input. Further, the subpopulation of NTS neurones receiving input from cardiac afferents are excited by 5-HT, possibly by an action on 5-HT1A or 5-HT3 receptors. © 1997 Elsevier Science Ltd.

On the intercostal muscle compensation for diaphragmatic paralysis in the dog.

1. Paralysis of the diaphragm in the dog is known to cause a compensatory increase in activation of the inspiratory intercostal muscles (parasternal intercostals, external intercostals, and levator costae). The present studies were designed to assess the mechanism(s) of that compensation. 2. Complete, selective diaphragmatic paralysis was induced by injecting local anaesthetic into small silicone cuffs placed around the phrenic nerve roots in the neck. 3. Paralysis produced a decrease in tidal volume and an increase in arterial P(CO2) (P(a,CO2)). The increased hypercapnic drive was a primary determinant of the increased inspiratory intercostal activity. 4. However, paralysis also produced an increased inspiratory cranial displacement of the ribs. When this increased rib displacement was reduced to that seen before paralysis, it appeared that the increase in external intercostal and levator costae inspiratory activity was commonly greater than anticipated on the basis of the increased P(a,CO2). 5. Diaphragmatic paralysis after bilateral vagotomy also elicited disproportionate increases in inspiratory intercostal activity, thus indicating that these increases are not caused by vagal afferent inputs. 6. These observations are consistent with the idea that the intercostal muscle compensation for diaphragmatic paralysis is, in part, due to the release of an inhibition originating from the contracting diaphragm. This inhibition might arise in the diaphragmatic tendon organs.

Subdiaphragmatic vagotomy does not attenuate c-Fos induction in the nucleus of the solitary tract after conditioned taste aversion expression

After acquisition of a conditioned taste aversion (CTA) against sucrose, intraoral infusions of sucrose induce c-Fos-like immunoreactivity (c-FLI) in the medial intermediate nucleus of the solitary tract (iNTS) of the rat. In order to determine if c-FLI expression in the iNTS depends on subdiaphragmatic vagal afferent input to the NTS secondary to gastrointestinal symptoms during CTA expression (e.g. diarrhea), we quantified the induction of c-FLI in the iNTS by sucrose infusions after total subdiaphragmatic vagotomy in rats with a previously acquired CTA against sucrose. Rats were conditioned against intraoral infusions of sucrose by pairing sucrose infusions with toxic LiCl injections. After CTA acquisition, rats underwent bilateral subdiaphragmatic vagotomy or were sham-vagotomized. One week after surgery, rats received an intraoral infusion of sucrose. One hour after the test infusion, rats were perfused and processed for c-FLI. Vagotomy had no apparent effect on the behavioral expression of the previously acquired CTA, because both vagotomized and sham-vagotomized rats rejected all of the test intraoral infusion of sucrose. There was also no significant difference between vagotomized and sham-vagotomized rats in the number of c-FLI-positive cells in the iNTS after CTA expression. We conclude that c-FLI induction correlated with CTA expression is not dependent on subdiaphragmatic vagal efferent output or afferent input.

Interactions of gastric vagal and peripheral nerves on single neurons of lateral hypothalamus in the cat.

Extracellularly recorded unitary responses in the lateral hypothalamus were evaluated in anesthetized cats during electrical stimulation of the gastric branches of the ventral and dorsal vagal trunks, the T9 intercostal nerve, and the common peroneal nerve (L6-S2). These nerves were stimulated with single or paired (10-ms interval) pulses of 300-500 microA for 0.3 ms at a frequency of 0.5 Hz. The latency of the evoked lateral hypothalamic responses after stimulation of the gastric vagal branches (373 +/- 39.8 ms; means +/- SD) was significantly longer than the latencies after intercostal nerve (62 +/- 17.0 ms) or common peroneal nerve (109 +/- 29.3 ms) stimulation. Convergence of gastric vagal input from the proximal stomach and peripheral nerves (PNs) on single neurons in the lateral hypothalamus was observed. Ninety-two percent of the lateral hypothalamic neurons tested that responded to gastric vagal stimulation also received inputs from the T9 intercostal nerve. Seventy-seven percent of the lateral hypothalamic gastric vagally evoked unitary responses received convergent inputs from the intercostal nerve and the common peroneal nerve. A condition-test paradigm was applied to determine the time course of convergent gastric and PN input on single lateral hypothalamic neurons. The test revealed that stimulation of the T9 intercostal nerve had a more pronounced effect than common peroneal nerve stimulation on the lateral hypothalamic neurons that receive gastric vagal input. The results demonstrated that gastric vagal afferent and PN inputs converge onto single lateral hypothalamic neurons and suggested that the central processing of visceral input from the stomach can be substantially affected by peripheral nerve stimulation.

1616 Influences of vagal afferent inputs on respiratory rhythm during induced vocalization

1616 Influences of vagal afferent inputs on respiratory rhythm during induced vocalization

Neurons in the dorsal motor nucleus of the vagus may integrate vagal and spinal information from the GI tract.

Previous investigations have provided evidence that the activity of parasympathetic efferent neurons in the dorsal motor nucleus of the vagus (DMNV) may be influenced by either vagal afferent or spinal input from the gastrointestinal (GI) tract. Many questions remain, however, regarding the nature of this input and its integration by the brain stem. The present study was designed to examine one important aspect of this issue: the potential contribution of the spinal input to the brain stem in the generation of the response properties of intestine-sensitive neurons in the DMNV. Using intracellular recording and labeling techniques in adult rats, we found that ascending spinal pathways were capable of conveying both low- and high-threshold visceral information to the DMNV. We also determined that the neurons in the nucleus of the solitary tract failed to respond to intestinal distention when the vagal afferents to the brain stem had been severed, suggesting that the spinal projections terminate directly on the DMNV neurons. These data lend support to the emerging hypothesis that the spinal afferents that accompany the abdominal splanchnics are capable of responding to both innocuous and noxious stimuli. The results also suggest that the neurons in the DMNV play a larger role in the integration of visceral sensory information than was previously realized.

Modulation of TCDD-induced wasting syndrome by portocaval anastomosis and vagotomy in Long-Evans and Han/Wistar rats

Portocaval anastomosis and vagotomy operations were performed in Long-Evans (L-E) and Han/Wistar (H/W) rats to elucidate the mechanism of anorexia induced by TCDD (2,3,7,8-tetrachlorodibenzo- p-dioxin). TCDD-sensitive L-E rats were given a sublethal (5 μg/kg) or a lethal dose (20 μg/kg) by gavage 5–8 weeks after portocaval anastomosis. TCDD-resistant H/W rats were given a nonlethal dose (500 or 7200 μg/kg). The shunt operation did not reduce lethality from TCDD. The effect on wasting of the marginally toxic dose of 5 μg/kg in L-E rats was potentiated by the portocaval operation, and the lethal dose was effective in both shunted and sham-operated L-E rats. TCDD failed to decrease food intake and body weight in shunted rats of H/W strain at either dose level though it did so in sham-oprated controls. The lack of effect may be due to the already reduced weight of shunted rats at the time of TCDD dosing. TCDD anorexia was not explained by changes in histamine or serotonin (5-HT) turnover in the brain. Vagotomy did not influence lethality after TCDD, although reduction in food intake was somewhat blunted in H/W rats. The results seem to indicate that the anorectic effect of TCDD is modified when portal blood bypasses the liver. The mechanisms remain to be elucidated in detail, but the results do not favor the role of liver as the only or the major initiator of TCDD anorexia. Little evidence was found to support a crucial role of vagal afferent input.

Vagal input enhances responsiveness of respiratory discharge to central changes in pH/CO2 in bullfrogs

This study investigated the interaction between vagal afferent input and central chemosensitivity in modulating the respiratory motor output of in vitro brain stem-spinal cord preparations from adult bullfrogs. With this preparation, the spatiotemporal distribution of respiratory-related motor output emulated that of intact bullfrogs; that is, the fictive breathing pattern was mostly episodic. Recordings from cranial motor nerves (V and X) showed that, without peripheral feedback, increasing the PCO2 of the mock cerebrospinal fluid (thereby reducing pH from 8.3 to 7.7) caused a modest increase in respiration-related burst frequency. When the pulmonary branch of a vagus nerve was stimulated phasically (2 V, 20 Hz, 0.2 ms) during each fictive breath to simulate afferent pulmonary stretch receptor feedback 1) the responsiveness of the preparation to the same changes in pH was augmented nearly threefold and 2) the breathing pattern remained episodic. It appears, therefore, that episodic breathing is an intrinsic property of the central nervous system in bullfrogs. It is concluded that there is a strong interaction between vagal feedback and central chemodetection in controlling the temporal relationships that characterize this episodic breathing pattern.