兔腹部迷走神经、内脏大神经活动在孤束核中的相互作用

本实验在67只家兔身上分别观察了电解损毁孤束核(NTS)前后刺激腹迷走神经和内脏大神经中枢端对血压的影响,以及刺激这两种神经中枢端对 NTS 神经元放电活动的影响。结果表明:来自腹迷走神经和内脏大神经的感觉冲动不仅都可以投射至 NTS,而且这两种传入冲动在 NTS 还存在着会聚现象。一种传入神经的阈下刺激(背景刺激)可以削弱另一传入神经的血压效应,一种传入神经的(背景刺激)可以抑制另一种神经元引起的 NTS 神经元电活动。本文对这两种传入冲动之间存在的相互作用关系的可能机制及意义进行了讨论。     

Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves]

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.     

Electrophysiology of the peripheral effect of two analgesics: aspirin and dibencozide

The peripheral effect of two analgesics (aspirin and dibencozide) was studied on anaesthetized cats. Several types of neurons and stimulations were performed in this work: traction for periodontal mechanoreceptors connected to small-sized trigeminal fibres, distension for the muscular intestinal mechanoreceptors connected to non-myelinated vagal fibres, chemical stimulation by means of phenyldiguanide for the non-myelinated vagal fibres, electrical stimulation of the myelinated and non-myelinated vagal fibres. In all cases, unitary activities were recorded into corresponding ganglia (nodose or gasserian) with extracellular glass microelectrodes. After injection of analgesics, a decrease of control responses were observed till 30 minutes but the maximum occurred between 1 and 5 minutes. This effect concerned the non-myelinated neurones as well as the myelinated ones. It can be explained by a direct action of analgesics on the ending excitability.     

Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields

Mechano- and chemosensitive extrinsic primary afferents innervating the gastrointestinal tract convey important information regarding the state of ingested nutrients and specific motor patterns to the central nervous system via splanchnic and vagal nerves. Little is known about the organization of peripheral receptive sites of afferents and their correspondence to morphologically identified terminal structures. Mechano- and chemosensory characteristics and receptive fields of single vagal fibers innervating the stomach as well as lumbar splanchnic nerves innervating the distal colon were identified using an in vitro perifusion system. Twenty-three (17%) of one-hundred thirty-six vagal units identified were found to have multiple, punctate receptive fields, up to 35 mm apart, and were distributed throughout the stomach. Evidence was based on similarity of generated spike forms, occlusion, and latency determinations. Most responded with brief bursts of activity to mucosal stroking with von Frey hairs (10-200 mg) but not to stretch, and 32% responded to capsaicin (10(-5) M). They were classified as rapidly adapting mucosal receptors. Four (8%) of fifty-three single units recorded from the lumbar splanchnic nerve had more than one, punctate receptive field in the distal colon, up to 40 mm apart. They responded to blunt probing, particularly from the serosal side, and variously to chemical stimulation with 5-hydroxytryptamine and capsaicin. We conclude that a proportion of gastrointestinal mechanosensors has multiple receptive fields and suggest that they integrate mechanical and chemical information from an entire organ, constituting the generalists in visceral sensation.     

Regulation of glycogen metabolism in liver by the autonomic nervous system. VI. Possible mechanism of phosphorylase activation by the splanchnic nerve.

The effects of autonomic-nerve stimulation on the activities of phosphorylase (EC 2.4.1.1), dephospho-phosphorylase kinase (EC 2.7.1.38) and phosphorylase phosphatase (EC 3.1.3.17), and on the concentration of adenosine 3', 5'-monophosphate in rabbit liver were investiaged. Results were compared with the effects of epinephrine and glucagon on these enzymes. 1. The acitivity of liver phosphorylase increased rapidly and markedly on electrical stimulation of the splanchnic nerve, or after intraportal administration of epinephrine or glucagon. The activity was not affected by vagal stimulation. 2. The activity of dephospho-phosphorylase kinase increased about 2--3-fold 1 min after injections of epinephrine and glucagon, glucagon causing more activation than epinephrine. The enzyme activity was not altered by splanchnic-nerve, or vagal stimulation. 3. Injections of epinephrine and glucagon caused marked elevation of liver adenosine 3', 5'-monophosphate within a few minutes. With epinephrine, the nucleotide concentration rose to a maximum after 1 min and amounted to about 3-fold increase, while with glucagon the maximum increase of approximately 8-fold increase was observed after 2 min. Stimulation of the splanchnic nerve for 10 min did not affect the adenosine 3', 5'-monophosphate level in the liver. Vagal stimulation also had no effect on the level. 4. The activity of phosphorylase phosphatase decreased promptly (within 30 s) and markedly on splanchnic-nerve stimulation, but did not change significantly on administration of epinephrine of glucagon. A small but insignificant increase in phosphatase activity wasobserved upon vagal stimulation. 5. The effect of Ca-2+ on purified dephospho-phosphorylase kinase was studied. The activity was found to depend partially on free Ca-2+ at low Ca-2+ concentrations (1-10-minus 7--1-10-minus 5 M). 6. These results suggest that the rise in hepatic phosphorylase content upon splanchnic-nerve stimulation, unlike that induced by epinephrine and glucagon, is not mediated by adenosine 3', 5'-monophosphate and subsequent activation of dephospho-phosphorylase kinase, but rather by inactivation of phosphorylase phosphatase. The possible existence of a new factor in this mechanism is discussed.     

Possible mechanisms of the anterior limbic cortex influence on the neuron activity of the vago-solitary complex

In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.     

Septal nuclei in the regulation of vago-sensitive neurons activity of the solitary nucleus in cats

The descending influences of the septal nuclei (lateral nucleus--LSN and bed nucleus stria terminalis--BNST) on activity of viscero-sensory neurons of the nucleus of tractus solitarius (NTS) identified by stimulation of cervical part of the n. vagus were investigated in the cat anaesthetised by chloraloze-nembutal combination. It was found that out of 70 units recorded in the NTS area 50 were identified as those of primary and secondary input vagal neurons. Influence of single, paired and frequency stimulation on the septal structures was studied on these neurons. It was revealed that 30% (15 un) reacted by phase-specific response to the single stimulation of the septal nuclei. The latent period of initial excitation was in the range 5-25 ms. During the paired stimulation these neurons were not able to react to the second stimulus for the equal 10-300 ms. It was revealed that 34% (17 un) of the identified vagal neurons reacted by a tonic change of their spontaneous activity. The increase of frequency stimulation to 20 Hz evoked different changes of the rhythmical activity of the vagal neurons (increase, diminishing or inhibition). The study of interaction between central and peripheral signals in the solitary neurons induced blocking influence of descending septal discharge on the vagal test response. It is possible that the septal downward impulses reach the vago-sensitive solitary neurons indirectly through other structures of the limbic brain (amygdala, hypothalamus) and participate in modulation of the spontaneous activity of these neurons.     

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons.

In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin beta-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) cholinergic neurons innervating the airways coexpress ChAT and VIP but do not contain NOS, and 3) chemical stimulation of the rostral nucleus ambiguus had no significant effect on precontracted airway smooth muscle tone after muscarinic receptor blockade. These studies indicate that vagal preganglionic neurons are cholinergic in nature and coexpress VIP but do not contain NOS; their stimulation increases cholinergic outflow, without activation of inhibitory nonadrenergic, noncholinergic ganglionic neurons, stimulation of which induces airway smooth muscle relaxation. Furthermore, these studies do not support the possibility of direct inhibitory innervation of airway smooth muscle by vagal preganglionic fibers that contain VIP.     

Primary Vagal Projection to the Contralateral Non-NTS Region in the Embryonic Chick Brainstem Revealed by Optical Recording

Using multiple-site optical recording with the voltage-sensitive dye, NK2761, we found that vagus nerve stimulation in the embryonic chick brainstem elicits postsynaptic responses in an undefined region on the contralateral side. The characteristics of the contralateral optical signals suggested that they correspond to the monosynaptic response that is related to the vagal afferent fibers. The location of the contralateral response was different from the vagal motor nucleus (the dorsal motor nucleus of the vagus nerve) and sensory nucleus (the nucleus of the tractus solitarius), and other brainstem nuclei that receive primary vagal projection. These results show that the vagus nerve innervates and makes functional synaptic connections in a previously unreported region of the brainstem, and suggest that sensory information processing mediated by the vagus nerve is more complex than expected.     

Influence of peripheral targets on the expression of calcitonin gene-related peptide immunoreactivity in rat cranial motoneurones

Calcitonin gene-related peptide-like immunoreactivity (CGRP-ir) is displayed by motoneurons that innervate striated muscle but is absent from preganglionic parasympathetic motoneurons. One hypothesis to explain this is that CGRP gene expression in motoneurons is, in part, dependent on influences from the innervated organ. To test this hypothesis, we cross-anastomosed the right hypoglossal and cervical vagal nerves of rats so that the vagal motoneurons grew to innervate the musculature of the tongue. Following a recovery period of 17 to 52 weeks, the distribution of CGRP-ir in the dorsal motor vagal nucleus was determined in both cross-anastomosed animals and self-anastomosed control animals. Successful reinnervation of the tongue musculature by vagal motoneurons was demonstrated by showing that electrical stimulation of the central vagus/peripheral hypoglossal nerve produced a twitch of the tongue muscles. Motoneurones of the dorsal motor vagal nucleus, which now innervated the tongue were found to express CGRP-ir, which was evident from the double labeling of neurons with both horseradish peroxidase and CGRP-ir. Motoneurones of the dorsal motor vagal nucleus contralateral to the cross-anastomosis remained CGRP negative. Similarly, motoneurons of the dorsal motor vagal nucleus in control animals where the vagus nerve was self-anastomosed remained CGRP negative, showing that an induction of CGRP expression is not a result of nerve section itself. We suggest that a signal from the striated muscle transported retrogradely via the motor axon regulates expression of CGRP-ir in motoneurons. © 1995 John Wiley & Sons, Inc.     

刺激家兔腹部迷走神经外周端降压效应中枢机制的研究

应用电解损毁和脑室内注射药物的方法研究了刺激家兔腹部迷走神经外周端所致降压效应的中枢机制。结果表明:1.电刺激延脑闩部尾侧1.5—2mm、中线旁开0.25mm、深1—2mm 处主要引起降压反应。2.电解损毁该部位可以使刺激腹部迷走神经外周端所引起的降压效应显著减弱(n=20,P<0.001),但对刺激减压神经所致降压反应无影响。3.在延脑闩部水平电解损毁减压神经纤维在孤束核的主要投射区可以使刺激减压神经所致降压反应显著减弱,而对刺激腹部迷走神经外周端所致降压反应无影响。4.第四脑室注射5,6-双羟色胺的动物较之注射人工脑脊液的动物颈、胸髓5-羟色胺含量明显降低、动物动脉压增高、心率明显增快、刺激减压神经所致降压反应未见减弱,而刺激腹部迷走神经外周端所致降压反应却明显减小。因此,我们认为家兔腹部迷走神经外周端所致降压效应依赖于延脑闩下部的中缝隐核及连合核等结构,而与减压神经的投射部位无关。延脑中缝核至脊髓的下行性5-HT能神经纤维抑制脊髓交感节前神经元的活动,是这个降压效应的中枢机制之一。     

Effects of bulbar stimulation on smooth muscle tone in the feline airway

Changes induced in tracheal smooth muscle tone by bulbar electrical stimulation were investigated in 30 cats anesthetized with a chloralose-urethane mixture and paralyzed with succinyl choline bromide. Raised tonus was mainly observed during stimulation of the caudal section of the dorsal motor nucleus of the vagus nerve, the vicinity of the nucleus ambiguus, and the adjoining reticular formation structures. Attenuation, however, was produced by stimulating bulbar reticular formation nuclei at a level 1 mm caudal and 6 mm rostral to the obex. Raised tonus is thought to be connected with activation of efferent neurons belonging to the motor nucleus of the vagal nerve, as well as axons of nucleus ambiguus neurons in transit through the medial zone, whilst attenuation is connected with excitation of sympathotonic reticular neurons, inhibitory neurons activated by pulmonary stretch receptors, and possibly with vagal efferent neurons activating the non-adrenergic inhibitory nervous system of the bronchi.Medical Institute, Latvian Ministry of Health, Riga. Cardiology Research Institute. Latvian Ministry of Health, Riga. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 320–326, May–June, 1989.     

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.     

Neurons in the rat lateral hypothalamic area integrate information from the gastric vagal nerves and the cerebellar interpositus nucleus

Previous investigations have demonstrated that the neuronal activity in the lateral hypothalamic area (LHA) is respectively modulated by afferent inputs from the gastric vagal nerves innervating the upper gastrointestinal tract, as well as the cerebellar interpositus nucleus (IN). The aim of this study was to examine whether the gastric vagal and cerebellar IN inputs converge onto single LHA neurons in rats, especially those sensitive to glycemia. Of the 114 LHA neurons recorded, 60 (52.6%) and 51 (44.7%) responded to gastric vagal and cerebellar IN stimulation, respectively. Of the 60 LHA neurons responsive to gastric vagal stimulation, 30 also responded to the cerebellar IN stimulus, indicating a convergence of gastric vagal and cerebellar inputs onto single hypothalamic cells. When the gastric vagal nerves and cerebellar IN were stimulated simultaneously, a summation of the responses was observed in all 6 neurons tested. Moreover, of 24 neurons that responded to both the gastric vagal and cerebellar IN stimuli, 15 (62.5%) were identified as glycemia-sensitive. These results demonstrate that the visceral information transmitted by the gastric vagal nerves and the somatic information forwarded by the cerebellar IN converge onto single LHA neurons, especially those sensitive to glycemia. The findings also suggest that integration of somatic-visceral responses related to short-term feeding regulation may take place in the LHA.     

Hydrolysis, synthesis, and release of acetylcholine in the isolated heart

The occurrence of unhydrolyzed acetylcholine (ACh) in the cardiac perfusate during vagal stimulation in the absence of cholinesterase inhibition has been demonstrated by several methods. Because some ACh was found unhydrolyzed in the extracellular space for several seconds after vagal stimulation (half-time of decay 2.5 s), it appears that the prolonged time course of the cardiac responses to bursts of vagal activity is determined by a slow rate of transmitter inactivation (diffusion plus hydrolysis) in addition to slowly operating postsynaptic mechanisms mediated by activation of the muscarinic receptor. The neuronal uptake of choline in isolated heart preparations was found to be Na+ dependent, sensitive to hemicholinium 3, and activated by vagal stimulation. Activation occurred after a delay of 1 or 2 min and slowly faded within 5 min after stimulation. Resting release of ACh was insensitive to extracellular Ca2+ and to muscarinic feedback inhibition, in contrast to the evoked transmitter release. Inasmuch as atropine increased ACh release by vagal and field stimulation to the same extent, muscarinic feedback inhibition is likely to occur at postganglionic parasympathetic neurons. Adrenergic agonists and propranolol did not significantly change the release of ACh.     

Corticofugal influences on postsynaptic processes in rubrospinal neurons in the cat brain

Composite and unitary EPSPs of red nucleus neurons evoked by stimulation of the sensomotor and association parietal cortex and nucleus interpositus of the cerebellum were studied in acute experiments on cats anesthetized with pentobarbital. A monosynaptic connection was shown to exist between not only the sensomotor, but also the association cortex, and rubrospinal neurons, in which unitary EPSPs appeared during stimulation of the association cortex after a latent period of 1.5–2.7 msec, with a peak rise time of 1.1–3.1 msec and an amplitude of 0.22–0.65 mV. Analysis of the temporal characteristics of the unitary EPSP suggested that synapses formed by fibers from the association cortex occupy a position nearer the soma than synapses formed by axons of sensomotor cortical cells.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 67–74, January–February, 1984.     

Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: physiological properties

Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8-T10 in the cat were compared according to a number of physiological properties. An SPN was classified as "adrenal" (n = 37) if it could be antidromically activated by electrical stimulation of the adrenal medulla. An SPN that could not be activated from the adrenal medulla yet could be antidromically activated by electrical stimulation of the greater splanchnic nerve was classified as "nonadrenal" (n = 123). Approximately 50% of adrenal SPNs (17 out of 37) were activated antidromically by stimulation of both the greater splanchnic nerve and adrenal medulla, suggesting that these neurones projected to the adrenal medulla via the greater splanchnic nerve, with the other adrenal SPNs taking a different route. The mean conduction velocities of adrenal (6.7 +/- 1.8 (SD) m/s) and nonadrenal (6.7 +/- 1.5 m/s) sympathetic preganglionic axons were similar. Over 80% of adrenal (31 out of 37) and nonadrenal (104 out of 116) SPNs were spontaneously active. The two types of neurone were indistinguishable in terms of the rates and patterns of discharge. Adrenal SPNs discharged with a mean rate of 1.4 +/- 1.1 spikes/s, and nonadrenal SPNs discharged with a mean rate of 1.8 +/- 1.4 spikes/s. With both types of SPN, the pattern of spontaneous activity was either irregular or phasic. With the latter pattern, periodic bursts of discharge were at the same frequency as oscillations in arterial pressure, frequency of ventilation, or phrenic nerve discharge. These data suggest that adrenal and nonadrenal sympathetic preganglionic neurones in the intermediolateral nucleus in caudal thoracic segments share a number of common physiological properties.     

刺激大鼠尾核对丘脑束旁核躯体-内脏会聚神经元放电的影响

实验记录大鼠丘脑束旁核躯体-内脏会聚(PfSV)神经元伤害性放电。观察刺激尾核(Cd)对 PfSV 神经元放电的影响。(1)Cd 对刺激内脏大神经诱发 PfSV 神经元伤害性放电有抑制作用(n=19)。(2)Cd 对刺激腓浅神经和内脏大神经诱发同一 PfSV 神经元伤害性放电均有抑制作用(n=11)。结果提示,躯体和内脏痛觉信息可会聚到丘脑束旁核同一神经元,Cd 可能不仅能抑制躯体痛也能抑制内脏痛。     

Neuropeptides as central integrators of autonomic nerve activity: effects of TRH, SRIF, VIP and bombesin on gastric and adrenal nerves

The nerve activity of the gastric ramus of the splanchnic (sympathetic) nerve, gastric ramus of the vagus, adrenal ramus of the splanchnic nerve and the superior laryngeal nerve (laryngeal ramus of vagus) were assessed before and after i.c.v. injection of neuropeptides in the rat. TRH stimulated the vagal branch but attenuated the sympathetic outflow to the stomach. In contrast, the sympathetic outflow to the adrenal was enhanced by TRH. SRIF suppressed the activity of all the nerves studied. VIP did not affect the sympathetic outflow to the stomach while suppressing the gastric branch of the vagus. The adrenal sympathetic branch as well as the superior laryngeal nerve was stimulated by VIP. Bombesin suppressed both vagal and sympathetic outflow to the stomach but markedly stimulated the laryngeal branch of the vagus. The adrenal sympathetic nerve was either stimulated or attenuated slightly by bombesin. These results indicate that centrally administered neuropeptides produce reactions specific for each nerve.     

Modulation of the masseteric reflex by gastric vagal afferents

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.