Pharmacological characterization of lower esophageal sphincter relaxation induced by swallowing, vagal efferent nerve stimulation, and esophageal distention.

To characterize the neural pathways involved in lower esophageal sphincter relaxation, intraluminal pressures from the lower esophageal sphincter of the opossum were monitored during swallowing, vagal efferent nerve stimulation, and intraluminal balloon distention in the presence and absence of pharmacologic antagonism of putative neurotransmitters. The combination of atropine, hexamethonium, and 5-methoxydimethyltryptamine, which is known to block ganglionic transmission in the vagal inhibitory pathway to the lower esophageal sphincter, significantly antagonized LES relaxation induced by both swallowing and vagal stimulation, but did not affect the LES relaxation induced by balloon distention. Administration of the nitric oxide synthase inhibitor N omega nitro-L-arginine methyl ester, on the other hand, markedly inhibited LES relaxation induced by vagal stimulation, swallowing, and balloon distention, and this effect was reversed by administration of the nitric oxide synthase substrate L-arginine. These studies indicate that the distension-induced intramural pathway mediating LES relaxation does not involve ganglionic transmission similar to that of the vagal inhibitory pathway to the LES. However, the LES relaxation induced by all forms of stimuli appears to depend on nitric oxide as a final mediator.     

Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium

Despite the importance of vagal control over the ventricle, little is known regarding vagal efferent conduction and nerve terminal function in the postischemic myocardium. To elucidate postischemic changes in the cardiac vagal efferent neuronal function, we measured myocardial interstitial acetylcholine (ACh) levels by using in vivo cardiac microdialysis and examined the ACh responses to electrical stimulation of the vagi or local administration of ouabain in anesthetized cats. Sixty-minute occlusions of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion abolished electrical stimulation-induced ACh release (20.4 +/- 3.9 vs. 0.9 +/- 0.4 nmol/l; means +/- SE, P < 0.01). In different groups of animals, 60-min LAD occlusion followed by 60-min reperfusion decreased but did not completely abolish ouabain-induced release of ACh (9.2 +/- 1.8 vs. 3.9 +/- 0.7 nmol/l; P < 0.05). These results indicate that function of the vagal efferent axon was completely interrupted, whereas the local ACh release was partially suppressed in the postischemic myocardium. The postischemic disruption of vagal efferent neuronal function might exert deleterious effects on cardiac regulation.     

Anatomical relationship between neuropeptide-containing fibers and efferent vagal neurons projecting to the rat corpus.

Injections of the retrograde tracers into the posterior surface of the stomach at the greater curvature resulted in labelling of the right half of the dorsal motor nucleus of the vagus. Whereas injections into the anterior and posterior surfaces of the corpus resulted in bilateral labelling in the medulla. Immunocytochemical staining of the labelled sections using antisera to substance P was confined to a dense network of fibers within the dorsal motor nucleus of the vagus and the nucleus tractus solitarius with no cell bodies being detected. Calcitonin gene-related peptide-immunoreactivity was detected in nerve fibers in the nucleus tractus solitarius and cell bodies of the hypoglossal nucleus. Finally, neuropeptide Y-immunoreactivity was confined to nerve fibers within the vagal complex. Of the neurons labelled by the retrograde tracers injected into the corpus all were in close spatial contact with fibers containing substance P-immunoreactivity. A smaller number were associated with neuropeptide Y-containing fibers with a few adjacent to calcitonin gene-related peptide-immunoreactive fibers. These results indicate that substance P and neuropeptide Y may directly regulate efferent neurons controlling gastric motility and acid secretion. Calcitonin gene-related peptide, however, is unlikely to directly modulate the cell bodies of the neurons in the dorsal motor nucleus but may modulate the dendrites from these neurons in the nucleus tractus solitarius.     

Inhibitory effects of beta-alanine on the vagal efferent and afferent excitatory responses of the stomach to stimulation of vagal trunk in cats.

The effects of beta-alanine on the electrically evoked vagal efferent (hexamethonium-sensitive initial excitatory response) and afferent (hexamethonium-resistant delayed excitatory response) responses of the cat stomach were studied. beta-alanine (30 to 300 micrograms/kg, i.v.) dose-dependently inhibited both the efferent and afferent response. The IC50 values of beta-alanine on the efferent and afferent response were 296 +/- 65 micrograms/kg and 128 +/- 35 microgram/kg, respectively. Maximal inhibitory effects of beta-alanine (300 micrograms/kg, i.v.) appeared about 1 hr after the injection. Glycine and taurine (100 to 10,000 micrograms/kg) did not affect these responses. Treatment with hexamethonium (10 mg/kg, i.v.) prevented the efferent response, but augmented the afferent response. The treatment with hexamethonium abolished the inhibitory effect of beta-alanine on the afferent response. Both picrotoxin (100 and 500 micrograms/kg, i.v.) and bicuculline (2000 micrograms/kg, i.v.) antagonized the inhibitory effects of beta-alanine on the vagal efferent and afferent responses of the stomach. The present experiments clearly demonstrated that beta-alanine inhibited both the vagal efferent and afferent excitatory responses of stomach to electrical stimulation of vagal trunk in cats.     

Spatial properties of receptive fields of mechanosensitive primary afferent nerve fibers

Tactile sensation is rich and varied, requiring input from a variety of mechanoreceptors whose spatiotemporal aspects deserve careful study. Recent data for virtually every class of sensitive mechanoreceptor have revealed spatial inhomogeneities in sensitivity reflecting the distribution of sense organ terminals and the complexity of gradients in the complex spatial organization of receptive fields. Controlled surface parallel stimulation provides a means for examining sensitivity in a manner that may shed light on active tactile exploration and allow quantitative analysis of orientation, direction, and velocity properties underlying some aspects of feature extraction by the central nervous system.     

Taste cell responses in the frog are modulated by parasympathetic efferent nerve fibers

We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells.     

Unusual discharge patterns of single fibers in the pigeon's auditory nerve

Summary Extracellular recording from single auditory nerve fibers in the pigeon,Columba livia, revealed some unusual discharge patterns of spontaneous and evoked activity.Time interval histograms (TIHs) of spontaneous activity showed a random interval distribution in 73% of the auditory fibers (Fig. 1a). The remaining 27% revealed periodicity in the TIHs (Fig. 1b–e), determined by the characteristic frequency (CF) of a given fiber. Normally, those fibers had a CF<2.2 kHz. In both cases spontaneous activity was irregular.The time pattern of quasiperiodic spontaneous firing in different auditory fibers is described by three main types of autocorrelation histograms (ACHs; decaying, nondecaying, and modulated), reflecting the spontaneous oscillations of the hair cell membrane potential (Fig. 1b–d).Single-tone suppression in auditory fibers with quasi-periodic spontaneous activity was found (Figs. 2, 10) and it could be observed if the eighth nerve was cut. There was no suppressive effect in fibres with random spontaneous firing.The frequency selectivity properties of auditory fibers were studied by means of an automatic method. Both simple (Fig. 4) and complex (Figs. 7, 8) response maps were found. Apart from the usual excitatory area, complex response maps were characterized by suppressive areas lying either above (Fig. 7), below (Fig. 8e), or on both sides of the CF (Fig. 8a–c). Generally, complex response maps were observed for fibers showing quasiperiodic spontaneous activity (Figs. 7, 8).Input-output functions at frequencies evoking single-tone suppression were nonmonotonic, while they were always monotonic at frequencies near the CF (Fig. 12).No difference in sharpness was observed between normal frequency threshold curves (FTCs) and exitatory areas of complex response maps (Fig. 9).On-off responses evoked by suppressive stimuli were found (Figs. 2, 3). They had a periodic pattern determined by the CF and did not depend on the stimulus frequency (Fig. 3).Low-CF fibers were observed which changed their time discharge structure to tone levels about 45 dB lower than their thresholds at the CF (Fig. 6).The observed features of the discharge patterns of the pigeon's auditory fibers reflect the distinctive nature of the fundamental mechanisms of auditory analysis in birds that are connected with electrical tuning of the hair cells and probably with the micromechanics of the bird's cochlea.Abbreviations ACH autocorrelation histogram - BP base period - CF characteristic frequency - FTC frequency threshold curve - IHC inner hair cell - OHC outer hair cell - PSTH peristimulus time histogram - TIH time interval histogram     

Harmonic analysis of two-tone discharge patterns in cochlear nerve fibers

Discharges in cochlear nerve fibers evoked by low frequency phase-locked sinusoidal acoustic stimuli are synchronized to the stimulus waveform. Excitation and suppression regions of single units were explored using a stimulus composed of either a fixed intensity test tone at the characteristic frequency, a variable intensity interfering tone with a simple integer frequency relation to the characteristic frequency, or both. Compound period histograms were constructed from period histograms in response to normal and reversed polarity stimuli. Discharge patterns were characterized by Fourier components of the histogram envelopes. The two stimulus frequencies constituted the principal harmonics in the histogram envelopes and their combination accounted for observed rate changes. Suppression of the test tone harmonic as a function of interfering tone intensity was always seen; rate suppression was not. The harmonic was typically suppressed by 20–30 dB compared to the value for the test tone alone and often reached the 40–60 dB resolution limit of the experiment. Suppression plots were nearly linear on a power scale with an average slope of-0.8. The onset of suppression occurred for an interfering tone 9 dB greater on average than the test tone intensity. Information transfer through the peripheral system was described by the ratio of the principal harmonic amplitudes versus the ratio of the intensities of the two stimulus tones. These plots were nearly linear on a power scale with an average slope of 0.9. Neither the onset of suppression nor the slopes of the harmonic plots displayed strong dependence on characteristic frequency or interfering tone frequency. These features of harmonic behavior, however, are closely related to system nonlinearity. Comparison of measured harmonics to the predictions of two phenomenological models suggest the presence of complex nonlinear transformations in the peripheral auditory system.     

Tonic activity of parasympathetic efferent nerve fibers hyperpolarizes the resting membrane potential of frog taste cells

We investigated the relationship between the membrane potential of frog taste cells in the fungiform papillae and the tonic discharge of parasympathetic efferent fibers in the glossopharyngeal (GP) nerve. When the parasympathetic preganglionic fibers in the GP nerve were kept intact, the mean membrane potential of Ringer-adapted taste cells was -40 mV but decreased to -31 mV after transecting the preganglionic fibers in the GP nerve and crushing the postganglionic fibers in the papillary nerve. The same result occurred after blocking the nicotinic acetylcholine receptors on parasympathetic ganglion cells in the tongue and blocking the substance P neurokinin-1 (NK-1) receptors in the gustatory efferent synapses. This indicates that the parasympathetic nerve (PSN) hyperpolarizes the membrane potential of frog taste cells by -9 mV. Repetitive stimulation of a transected GP nerve revealed that a -9-mV hyperpolarization of taste cells maintained under the intact GP nerve derives from an approximately 10-Hz discharge of the PSN efferent fibers. The mean frequency of tonic discharges extracellularly recorded from PSN efferent fibers of the taste disks was 9.1 impulses/s. We conclude that the resting membrane potential of frog taste cells is continuously hyperpolarized by on average -9 mV by an approximately 10-Hz tonic discharge from the parasympathetic preganglionic neurons in the medulla oblongata.     

Bilateral distribution of vagal motor and sensory nerve fibers in the rat's lungs and airways

This study combined single and transneuronal labeling to define the origin of midline-crossing vagal fibers projecting to the rat's lungs. Injections of the beta-subunit of cholera toxin (CT-beta) into the lungs labeled similar numbers of neuronal somata in the nucleus ambiguus and dorsal motor nucleus of the vagus on both sides of the medulla, even though vagal stimulation increased lung resistance 50% less in the contralateral than in the ipsilateral lung. Unilateral cervical vagotomy prevented CT-beta labeling of ipsilateral neuronal somata and sensory fibers, indicating that lung-bound vagal fibers undergo decussation only inside the thorax. Injections of CT-beta and FluoroGold into opposite main stem bronchi double labeled 30% and 11% of all neuronal somata immunoreactive for CT-beta and FluoroGold, respectively, showing that one single vagal motoneuron can innervate airways on both sides. Injections of pseudorabies virus into the right lung revealed a bilateral network of infected neurons, even after unilateral vagotomy. The latter did not prevent infection of the ipsilateral vagal nuclei. These findings demonstrate that vagal motoneurons that project to the lungs receive contralateral inputs from the airway premotor network and vagal bronchomotor centers.     

Simulation of spontaneous discharge and short-term adaptation in acoustic nerve fibers

A model for firing of the auditory nerve fibres was carried out on a general purpose digital computer. In the model a noise with small correlation time and with assigned standard deviation (when modeling a spontaneous discharge) or a sum of a noise and a determinated signal (when modeling an elicited discharge) is compared with incremental threshold. When the threshold is exceeded a spike occurs and the threshold is increased. The threshold qualitative properties and quantitative values were chosen in a way to provide the most reliable patterns of spontaneous discharge, according to the literature data obtained from the cat's auditory nerve. When stimulated by tone-bursts the model reveals intrinsic ability of mimicking the phenomena of discharge rate short-term adaptation. Thus according to our model the short-term adaptation is entirely due to the properties of the incremental threshold.