Transduction sites of vagal mechanoreceptors in the guinea pig esophagus.

Extrinsic afferent neurons play an essential role in both sensation and reflex control of visceral organs, but their specialized morphological peripheral endings have never been functionally identified. Extracellular recordings were made from fine nerve trunks running between the vagus nerve and esophagus of the guinea pig. Mechanoreceptors, which responded to esophageal distension, fired spontaneously, had low thresholds to circumferential stretch, and were slowly adapting. Calibrated von Frey hairs (0.12 mN) were used to probe the serosal surface at 100-200 sites, which were mapped on a video image of the live preparation. Each stretch-sensitive unit had one to three highly localized receptive fields ("hot spots"), which were marked with Indian ink applied on the tip of the von Frey hair. Recorded nerve trunks were then filled anterogradely, using biotinamide in an artificial intracellular solution. Receptive fields were consistently associated with intraganglionic laminar endings (IGLEs) in myenteric ganglia, but not with other filled neuronal structures. The average distance of receptive fields to IGLEs was 73 +/- 14 microm (24 receptive fields, from 12 units; n = 5), compared to 374 +/- 17 microm for 240 randomly generated sites (n = 5; p < 0.001). After maintained probing on a single receptive field, spontaneous discharge of units was inhibited, as were responses to distension. During adapted discharge to maintained distension, interspike intervals were distributed in a narrow range. This indicates that multiple receptive fields interact to encode mechanical distortion in a graded manner. IGLEs are specialized transduction sites of mechanosensitive vagal afferent neurons in the guinea pig esophagus.     

Direct activation of guinea pig vagal afferent neurons by FMRFamide

Vagus nerve comprises two distinct kinds of nerves, nodose and jugular ganglionic nerves. We tested pharmacological difference between two vagal nerves in the responsiveness to FMRFamide. The response probability to FMRFamide was significantly higher in nodose than jugular nerves in intracellular calcium measurement. Nodose nerves also depolarized membrane potential to FMRFamide more than jugular nerves did, in patch-clamp recording, although the probability of action potential discharge was same in both nerves. The inward current induced by FMRFamide was characterized as mixed cations. These results suggest that FMRFamide may act as an activator and modulator of vagal sensory nerves for treating symptoms in visceral diseases.     

5-Hydroxytryptamine selectively activates the vagal nodose C-fibre subtype in the guinea-pig oesophagus

Abstract  The afferent neurons innervating the oesophagus originate from two embryonic sources: neurons located in vagal nodose ganglia originate from embryonic placodes and neurons located in vagal jugular and spinal dorsal root ganglia (DRG) originate from the neural crest. Here, we address the hypothesis that 5-hydroxytryptamine (5-HT) differentially stimulates afferent nerve subtypes in the oesophagus. Extracellular recordings of single unit activity originating from nerve terminals were made in the isolated innervated guinea-pig oesophagus. Whole cell patch clamp recordings (35 °C) were made from the primary afferent neurons retrogradely labelled from the oesophagus. 5-Hydroxytryptamine (10  μ mol L⁻¹) activated vagal nodose C-fibres (70%) in the oesophagus but failed to activate overtly vagal jugular nerve fibres and oesophagus-specific spinal DRG neurons. The response to 5-HT in nodose C-fibre nerve terminals was mimicked by the selective 5-HT₃ receptor agonist 2-methyl-5-HT (10  μ mol L⁻¹) and nearly abolished by the 5-HT₃ receptor antagonists ondansetron (10  μ mol L⁻¹) and Y-25130 (10  μ mol L⁻¹). In patch clamp studies, 2-methyl-5-HT (10  μ mol L⁻¹) activated a proportion of isolated oesophagus-specific nodose capsaicin-sensitive neurons (putative cell bodies of nodose C-fibres). We conclude that the responsiveness to 5-HT discriminates placode-derived (vagal nodose) C-fibres from the neural crest-derived (vagal jugular and spinal DRG) afferent nerves in the oesophagus. The response to 5-HT in nodose C-fibres is mediated by the 5-HT₃ receptor in their neuronal membrane.     

IL-1Ⅰ型受体在大鼠结状神经节及迷走旁节中的表达

为研究迷走神经感受和传递免疫信息的机制,用免疫组织化学方法研究了IL-1Ⅰ型受体在正常和免疫激活的大鼠结状神经节和迷走旁节中的表达.结果表明,正常大鼠结状神经节和迷走旁节中均存在IL-1Ⅰ型受体样免疫反应阳性的神经元,结状神经节中阳性神经元以中、小细胞为主;迷走旁节中几乎所有的细胞均呈IL-1Ⅰ型受体样免疫阳性.细菌内毒素脂多糖(lipopolysaccharide,LPS)刺激后结状神经节和迷走旁节中阳性细胞数量未见明显变化.本文结果为迷走神经的初级内脏感觉神经元和迷走旁节可直接感受IL-1刺激的学说提供了形态学基础.     

IL—1Ⅰ型受体在大鼠结状神经节及迷走旁节中的表达

为研究迷走神经感受和传递免疫信息的机制,用免疫组织化学方法研究了ＩＬ－１Ⅰ型受体在正常和免疫激活的大鼠结状神经节和迷走旁节中的表达。本文结果为迷走神经的初级内脏感觉神经元和迷走旁节可直接感受ＩＬ－１Ⅰ刺激的学说提供了形态学基础。     

Effects of TRPA1 activation and inhibition on TRPA1 and CGRP expression in dorsal root ganglion neurons

Transient receptor potential ankyrin 1(TRPA1) is a key player in pain and neurogenic inflammation, and is localized in nociceptive primary sensory dorsal root ganglion(DRG) neurons. TRPA1 plays a major role in the transmission of nociceptive sensory signals. The generation of neurogenic inflammation appears to involve TRPA1-evoked release of calcitonin gene-related peptide(CGRP). However, it remains unknown whether TRPA1 or CGRP expression is affected by TRPA1 activation. Thus, in this study, we examined TRPA1 and CGRP expression in DRG neurons in vitro after treatment with the TRPA1 activator formaldehyde or the TRPA1 blocker menthol. In addition, we examined the role of extracellular signal-regulated protein kinase 1/2(ERK1/2) in this process. DRG neurons in culture were exposed to formaldehyde, menthol, the ERK1/2 inhibitor PD98059 + formaldehyde, or PD98059 + menthol. After treatment, real-time polymerase chain reaction, western blot assay and double immunofluorescence labeling were performed to evaluate TRPA1 and CGRP expression in DRG neurons. Formaldehyde elevated mRNA and protein levels of TRPA1 and CGRP, as well as the proportion of TRPA1-and CGRP-positive neurons. In contrast, menthol reduced TRPA1 and CGRP expression. Furthermore, the effects of formaldehyde, but not menthol, on CGRP expression were blocked by pretreatment with PD98059. PD98059 pretreatment did not affect TRPA1 expression in the presence of formaldehyde or menthol.     

Denervation of vagal cardiopulmonary receptors by injection of kainic acid into the nodose ganglia in dogs

Intracellular studies previously conducted in our laboratory on adult rats indicate that the activity of spinally projecting RVL neurons (neurons located in the Rostral Ventrolateral Medulla) results from synaptic inputs. The data obtained by others in medullary slices suggest that the firing of these neurons (RVL C1 and/or non-C1 type, depending on experimental conditions) is mainly determined by their 'beating' pacemaker properties. Interestingly, there is an analogy between the contrasting views on the role of the network vs. pacemakers in the generation of sympathetic tone, and a debate regarding the relative role of such mechanisms in other types of 'spontaneously' active neurons, including dopaminergic neurons of the Substantia Nigra/Ventral Tegmental Area (in ventral mesencephalon). This short review discusses our previous in vivo studies and more recent data obtained in vitro after acute cell isolation, showing that under both experimental conditions, the RVL neurons display no clear pacemaker-like properties. Interestingly, pacemaker activity of dopaminergic mesencephalic neurons can be easily demonstrated in brain slices and after acute isolation, but not in vivo. These findings strongly suggest that under normal in vivo conditions, individual neurons belonging to these two neural systems function as elements of networks.     

Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat

Abstract  The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague–Dawley rats. Intravenous administration of GLP-1 (30–1000 pmol kg⁻¹), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13–52% above basal level, P  <   0.05) 3–5 min after injection. Repeated administration of GLP-1 (1000 pmol kg⁻¹; five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg⁻¹) abolished the GLP-1 response to doses 30–300 pmol kg⁻¹ but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg⁻¹) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.     

Neuronal surface changes in the dorsal vagal motor nucleus of the guinea pig in response to axotomy

Ultrastructural changes occurring in the dorsal motor nucleus of the vagus of the guinea pig after nerve transection were investigated. Two neuronal populations could be distinguished. Large neurons corresponding to the vagal motoneurons showed chromatolysis. They were found to develop complex changes in cell surface, which appeared either as a folding up and formation of flaplike processes or as invagination of adjacent neuronal or glial elements. Large processes often covered part of the plasmalemma and formed stacks of several neuronal lamellae. Smaller processes were mostly seen to extend into the neuropil, where they intermingled and adopted a budlike shape. These changes occurred in the cell somata within the first week after axotomy. The dendrites were affected after a short delay. The changes persisted for several months in most of the neurons, including the ones that showed signs of recovery from chromatolysis. The newly formed cellular extensions had a growth-cone-like internal structure, containing numerous smooth-surfaced vesicles or cisternae, a feltwork of filamentous material, dense-cored vesicles, and occasionally free polyribosomes. These surface changes did not occur in the second neuronal cell type of this nucleus, which had a smaller perikaryon characterized by a scanty cytoplasm. These cells did not show a retrograde degeneration and thus are probably interneurons. Acetylcholinesterase was used as a cytochemical marker of neuronal membranes. Surprisingly, the vagal motoneurons did not show a loss of enzymatic activity after nerve transection. Rather, a redistribution seemed to occur with intensified staining of the plasmalemma. The newly formed processes were consistently found to be acetylcholinesterase positive. It is suggested that the morphological changes observed correspond to an as-yet-unobserved growth process in the adult central nervous system, which involves perikarya and dendrites of regenerating guinea pig vagal motoneurons.     

Electrophysiological evidence for vestibular activation of the guinea pig hippocampus

Vestibular information modulates hippocampal activity for spatial processing and place cell firing. However, evidence of a purely vestibular stimulus modulating hippocampal activity is confounded as most studies use stimuli containing somatosensory and visual components. In the present study, high-frequency electrical stimulation of specific vestibular sensory regions of the right labyrinth in anaesthetized guinea pigs induced an evoked field potential in the hippocampal formation bilaterally with a latency of about 40 ms following stimulation onset. Field potentials localized in the hippocampal formation occurred with stimulus current parameters that were too small to produce eye movements. This provides direct electrophysiological evidence of vestibular input to the hippocampus.     

Functional GABAB receptors are present in guinea pig nodose ganglion cell bodies but not in peripheral mechanosensitive endings

The effects of the GABAB-selective agonist baclofen were studied on guinea pig nodose ganglion neurones using grease gap and intracellular recording techniques, and on peripheral mechanosensitive endings in the guinea pig oesophagus and stomach with extracellular recordings. GABA dose-dependently reduced the amplitude of the compound action potential of C-type neurones (C spikes, EC50 = 30.9 microM), which was prevented by the GABAA antagonist bicuculline (10 microM). The GABAB agonist baclofen (1-300 microM) did not produce any significant effect on the amplitude of C spikes. In microelectrode studies, baclofen (100 microM) evoked hyperpolarisation (by 2.53 +/- 0.51 mV, n = 6, N = 5) in a subset of nodose neurones (6 out of 26, N = 18). In seven out of eight neurones (N = 8) with a slow after-hyperpolarisation following action potentials, baclofen significantly inhibited its amplitude by 19 +/- 4% (n = 7, p < 0.05). GABA (100 microM) evoked a depolarisation of 9.3 +/- 2.4 mV (10 nodose neurones, N = 9, p < 0.05) associated with a decrease in input impedance of 49 +/- 12% (N = 4, p < 0.05). Baclofen (100-200 microM) did not affect either spontaneous or stretch-evoked firing of distension-sensitive vagal mechanoreceptors of the guinea pig oesophagus and stomach but did inhibit mechanoreceptors in the ferret oesophagus. Antibodies to GABAB receptor 1a splice variants labelled most of the neurones and numerous fibres in the guinea pig nodose ganglion while antibodies to GABAB receptor 1b splice variants stained only nerve cell bodies. There were numerous nerve fibres showing GABAB receptor 1a- and 1b-like immunoreactivity in the myenteric plexus in the guinea pig oesophagus and stomach but not in anterogradely labelled extrinsic vagal nerve fibres. The result indicates that most guinea pig C-type nodose ganglion neurones have GABAB receptors on their cell bodies but their density on distension-sensitive peripheral endings is too low to allow modulation of mechanotransduction. There is a significant species-dependent difference in the expression of GABAB receptors on peripheral vagal mechanosensitive endings.     

Distribution of vagal afferent fibers of the guinea pig heart labeled by anterograde transport of conjugated horseradish peroxidase.

To determine the distribution of vagal afferent fibers in the heart, wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) or choleragenoid conjugated horseradish peroxidase (B-HRP) was injected into nodose ganglia of guinea pigs. Anterogradely labeled fibers and beaded, terminal-like arborizations were observed in the ascending aorta and aortic arch, the pulmonary trunk and arteries, posterior atrial walls, atrioventricular valves, and ventricles. Control experiments with injection of B-HRP into the cervical vagus nerve indicated that labeled fibers observed in the heart originated from sensory neurons in the nodose ganglia. Neither the density nor distribution of labeling differed between WGA-HRP and B-HRP. Injection of tracer into the left or right nodose ganglion shows that these regions of the heart are bilaterally innervated, although labeling in the left or right posterior atrium was denser after injection into the ipsilateral ganglion. Comparison with a previous study on the distribution of sympathetic afferent fibers in the guinea pig heart suggests that the two afferent systems maintain a complementary, but not mutually exclusive, distribution within the ventricles. Whereas afferents with their source in the spinal ganglia are mainly distributed with coronary arteries on the anterior-superior surface of the ventricles, afferent fibers with their source in the nodose ganglia are concentrated within peri-arterial regions of the posterior-inferior ventricular epicardium and the posterior septal ventricular endocardium. These differences in distributions of afferent systems could play a role in post-infarction autonomic dysfunction and in the symptoms that accompany angina pectoris.     

N-methyl-D-aspartate receptor subunit phenotypes of vagal afferent neurons in nodose ganglia of the rat

Most vagal afferent neurons in rat nodose ganglia express mRNA coding for the NR1 subunit of the heteromeric N-methyl-D-aspartate (NMDA) receptor ion channel. NMDA receptor subunit immunoreactivity has been detected on axon terminals of vagal afferents in the dorsal hindbrain, suggesting a role for presynaptic NMDA receptors in viscerosensory function. Although NMDA receptor subunits (NR1, NR2B, NR2C, and NR2D) have been linked to distinct neuronal populations in the brain, the NMDA receptor subunit phenotype of vagal afferent neurons has not been determined. Therefore, we examined NMDA receptor subunit (NR1, NR2B, NR2C, and NR2D) immunoreactivity in vagal afferent neurons. We found that, although the left nodose contained significantly more neurons (7,603), than the right (5,978), the proportions of NMDA subunits expressed in the left and right nodose ganglia were not significantly different. Immunoreactivity for NMDA NR1 subunit was present in 92.3% of all nodose neurons. NR2B immunoreactivity was present in 56.7% of neurons; NR2C-expressing nodose neurons made up 49.4% of the total population; NR2D subunit immunoreactivity was observed in just 13.5% of all nodose neurons. Double labeling revealed that 30.2% of nodose neurons expressed immunoreactivity to both NR2B and NR2C, whereas NR2B and NR2D immunoreactivities were colocalized in 11.5% of nodose neurons. NR2C immunoreactivity colocalized with NR2D in 13.1% of nodose neurons. Our results indicate that most vagal afferent neurons express NMDA receptor ion channels composed of NR1, NR2B, and NR2C subunits and that a minority phenotype that expresses NR2D also expresses NR1, NR2B, and NR2C.     

Mechanosensory transduction of vagal and baroreceptor afferents revealed by study of isolated nodose neurons in culture

Changes in arterial pressure and blood volume are sensed by baroreceptor and vagal afferent nerves innervating aorta and heart with soma in nodose ganglia. The inability to measure membrane potential at the nerve terminals has limited our understanding of mechanosensory transduction. Goals of the present study were to: (1) Characterize membrane potential and action potential responses to mechanical stimulation of isolated nodose sensory neurons in culture; and (2) Determine whether the degenerin/epithelial sodium channel (DEG/ENaC) blocker amiloride selectively blocks mechanically induced depolarization without suppressing membrane excitability. Membrane potential of isolated rat nodose neurons was measured with sharp microelectrodes. Mechanical stimulation with buffer ejected from a micropipette (5, 10, 20 psi) depolarized 6 of 10 nodose neurons (60%) in an intensity-dependent manner. The depolarization evoked action potentials in 4 of the 6 neurons. Amiloride (1 microM) essentially abolished mechanically induced depolarization (15 +/- 4 mV during control vs. 1 +/- 2 mV during amiloride with 20-psi stimulation, n = 6) and action potential discharge. In contrast, amiloride did not inhibit the frequency of action potential discharge in response to depolarizing current injection (n = 6). In summary, mechanical stimulation depolarizes and triggers action potentials in a subpopulation of nodose sensory neurons in culture. The DEG/ENaC blocker amiloride at a concentration of 1 microM inhibits responses to mechanical stimulation without suppressing membrane excitability. The results support the hypothesis that DEG/ENaC subunits are components of mechanosensitive ion channels on vagal afferent and baroreceptor neurons.     

Hyposmotic activation hyperpolarizes outer hair cells of guinea pig cochlea

The electrophysiological responses of isolated guinea pig outer hair cells (OHCs) to hyposmotic activation were studied using the whole-cell patch-clamp technique. The cell swelling by hyposmotic activation hyperpolarized OHCs by 6.6 ± 2.3 mV from the resting membrane potential of −58.5 ± 5.9 mV (n = 48). This hyperpolarization was associated with an outward current ( 97.7 ± 22.2, pA, n = 15). The hyperpolarization was inhibited by 300 μM quinine, 5 mN Ba²⁺ and increasing the extracellular K⁺ to 30 mM from 5 mM. In the absence of extracellular Ca²⁺ (1 mM EGTA), the hyperpolarization during hyposmotic activation was also abolished while the following depolarization was preserved. 50 μM GdCl₃, which is known to block strecch-activated non-specific cation channels, inhibited the hyperpolarization reversibly. 50 μM GdCl₃ also inhibited [Ca²⁺]_i increase during hyposmotic activation as shown by the calcium-sensitive dye fura-2. Simultaneously, the [Ca²⁺]_i increase and the hyperpolarization during hyposmotic activation could be observed using the combined method of whole-cell patch clamp and fura-2 technique. It is concluded that the cell swelling by hyposmotic activation may activate the stretch-activated non-specific cation channels in the OHCs which allow a Ca²⁺ influx. In turn, this [Ca²⁺]_i increase leads to an activation of the Ca²⁺-activated K⁺ channels at the basolateral membrane of OHCs which results finally in a reversible hyperpolarization of OHCs by K⁺ efflux.     

Electrophysiological and morphological properties of type C vagal neurons in the nodose ganglion of the cat

Some passive and active electrical properties of type C neurons were studied intracellularly, in situ, in the nodose ganglia of adult cats. From the neuronal responses to hyperpolarizing and depolarizing rectangular current pulses it was possible to determine the input resistance (34.4 M omega) and specific membrane resistance (2373 omega.cm2). Significant changes in magnitude and duration of the action potential evoked by vagal stimulation result from changes in the resting potential caused by the passage of steady polarizing currents across the cell membrane. The action potentials evoked by infranodose vagal stimulation had a long duration, a long latency and comprised several components. The fast main spike was followed by a long post-hyperpolarization. The double shock technique showed that the fast main potential was composed of an initial segment spike ('A spike') and a somatic spike ('S spike'), and made it possible to determine the somatic refractory periods. After electrical identification of the cells, horseradish peroxidase was injected ionophoretically into the soma, and it was shown that the central processes were about four times smaller in diameter than the peripheral processes.     

Serotoninergic activation of the basolateral amygdala and modulation of tonic immobility in guinea pig

Tonic immobility (TI), also known as death feigning or animal hypnosis, is a reversible state of motor inhibition that is not only triggered by postural inversion and/or movement restraining maneuvers but also by repetitive stimulation and pressure on body parts. Evidence has demonstrated that the basolateral nucleus of the amygdala (BLA) is particularly associated with defensive behavior that involves the emotional states of fear and anxiety. In addition, some reports have demonstrated that serotonin (5-HT) released in the amygdala is increased during states of stress and anxiety, principally in the BLA. In the present study, we investigated the effects of serotonergic activation of the BLA on the duration of TI. The results showed that the microinjection of 5-HT (3.0 microg) into the BLA decreased the duration of TI. Similarly, the administration of a 5-HT1A agonist (0.1 microg of 8-hydroxy-dipropylaminotretalin) or 5-HT2 agonist (0.1 microg of alpha-methyl-5-HT) into the BLA reduced the TI duration. The effect of 5-HT2 agonist was reversed by pretreatment with a dose that had no effect per se (0.01 microg) of ketanserin (5-HT2 receptor antagonists) into the BLA. Moreover, the activation of 5-HT1A and 5-HT2 receptors in the BLA did not alter the spontaneous motor activity in the open field test. The results of the present study indicate that the serotonergic system of the BLA possibly produces a reduction in fear and/or anxiety that reduces the TI duration in guinea pigs, but this is not due to increased spontaneous motor activity induced by serotonergic activation, which might affect TI duration non-specifically.     

Time course and distribution of motoneuronal loss in the dorsal motor vagal nucleus of guinea pig after cervical vagotomy

Cells in the dorsal motor vagal nucleus (DMVN) of the adult guinea pig were counted at different times after unilateral cervical section of the vagus nerve. The counts were made from serial 30 μm coronal sections throughout the DMVN in normal and operated animals. There are three types of cells in the DMVN of guinea pig: medium-sized motoneurons that are retrogradely filled by HRP from the site of the vagotomy, small neurons, and glial cells. An interesting observation was a change in distribution of cells in the DMVN with age in unoperated guinea pigs. Following vagotomy degeneration was seen only in the motoneurons. Disappearance of motoneurons was slow and only 27% were present after 1 year. During that time the decrease in the total number of motoneurons was exponential with a time constant of 8.6 months, but degeneration in different parts of the nucleus was not uniform. Thirty-four percent of motoneurons in the caudal area of DMVN disappeared in the first month after vagotomy, while the rostral area was almost unchanged. The rostral area, however, showed rapid degeneration between 3 and 6 months after vagotomy. The central part of the nucleus degenerated at a constant rate between those of the rostral and caudal regions. At the end of 1 year, cell loss in all parts of the nucleus was approximately equal. Surviving motoneurons showed morphological changes: rounding of the soma, continuous reduction of the cell volume, and shrinkage of the nucleus. Occasional abnormal forms showing vacuolization or invaginated nuclei were seen. Calculations show that the process of degeneration lasts 25 days on the average. The marked degeneration found in dorsal vagal motoneurons, in contrast to recovery from axotomy in somatic motoneurons, is similar to that found in intrinsic neurons of the central nervous system. The slow and continuous time course of disappearance of motoneurons after vagotomy, however, is exceptional. It is reasonable to postulate that the increased vulnerability of these motoneurons may be sufficient to result in degeneration in response to what are normally nonpathological metabolic demands.     

Evidence of substance P immunoreactive neurons in dorsal root ganglia and vagal ganglia projecting to the guinea pig pylorus

The origin of extrinsic substance P fibers in the guinea pig pyloric wall was investigated by combining retrograde axonal tracing and indirect immunofluorescence techniques. After injection of Fast Blue into the pyloric wall labeled cells were found in the T7-T9 dorsal root ganglia and the nodose and jugular ganglia. About 60% of the labeled cells in the dorsal root ganglia contained substance P-like immunoreactivity. After local application of colchicine, a few substance P positive cells were observed in the nodose and jugular ganglia, some of which also contained Fast Blue.