Noradrenergic alpha 2 binding sites in vagal dorsal motor nucleus and nucleus tractus solitarius: autoradiographic localization

The distribution in the canine medulla oblongata of binding sites for p-[3H]aminoclonidine, a ligand specific for alpha 2-adrenergic receptors, was studied with light microscopic autoradiographic methods. Specific labelling was determined using unlabelled phentolamine as a displacer. The greatest density of sites was localized in the dorsal motor nucleus of the vagus nerve, the area postrema, and in several regions of the nucleus tractus solitarius. Less dense binding of the radioligand was also seen in the inferior olivary nucleus. Dorsomedial regions of the nucleus tractus solitarius were the most densely labelled in this nucleus, and dorsolateral and ventral regions were much less densely labelled. The region of the nucleus tractus solitarius shown in this study to be heavily labelled with alpha 2-adrenergic binding sites has been implicated in the autonomic control of blood pressure. The dorsal motor nucleus of the vagus, together with the nucleus tractus solitarius, may thus represent the site of the antihypertensive action of the drug clonidine, an alpha 2-adrenoreceptor agonist.     

Functional characteristics of neuropeptides in the dorsal medulla oblongata and vagus nerve

The dorsomedial medulla plays an integral role in the processing of primary sensory afferent information from the respiratory, cardiovascular, and gastrointestinal systems. A correlation has also been made between the topographical organization of these vagal afferent fibers in the dorsal medulla and the distribution of a variety of neuropeptides and their receptors in this brain region. In this paper, the evidence for the presence of several neuropeptides and their receptors in the dorsomedial medulla and intra- and/or extracranial segments of the vagus nerve is presented. The possible physiological significance of these peptides and their putative receptors in the vagus nerve is also addressed, with emphasis on angiotensin II and its cardiovascular actions in this region.     

Cellular reaction of the area postrema of the medulla oblongata to experimental alloxan diabetes

The karyometric method was used to investigate the response of the ependyne nerve and glia-like cells of the rat area postrema (AP) to disorders of carbohydrate metabolism in alloxan diabetes. A significant response of these cells was revealed, which was also confirmed by the changes found in the AP structures in disorders of glucose metabolism. The data obtained are consistent with the hypothesis that the AP structures are implicated in the regulation of carbohydrate metabolism as chemoreceptor ones.     

Changes in the alpha-adrenoceptors in the medulla oblongata including nucleus tractus solitarii of spontaneously hypertensive rats

The nucleus tractus solitarii (NTS) is a brain stem center mediating depression of blood pressure. In order to elucidate a possible mechanism for the central regulation of blood pressure, we studied noradrenergic indices in the medulla oblongata, a region including the NTS, in spontaneously hypertensive rats (SHR) as compared with normotensive controls of the Wistar Kyoto strain (WKY) at 12 weeks of age. The medulla oblongata was the only brain region showing a significantly low noradrenaline level in the SHR as compared with WKY rats; the level is also significantly decreased at 8 weeks of age. The alpha 1-adrenergic binding sites, as measured with 2-(2, 6-dimethoxy) phenoxyethylamine-methylbenzodioxan [³H]WB4101 showed significant increases inK _D andB _max values in medulla oblongata homogenates from rats of both strains from 4–12 weeks after birth, with no significant interstrain difference. On the other hand, theK _D andB _max of the alpha 2-sites, measured by [³H]yohimbine binding, were reduced in SHR as compared to WKY animals, even at 4 weeks after birth when hypertension was not yet apparent. As expected, the relatively selective alpha 2-antagonist, clonidine, was a potent inhibitor of [³H]yohimbine binding but not of [³H]WB4101 binding in these homogenates. The results suggest that some genetic disorder in the alpha 2-adrenergic transmission system in the NTS region may be involved in the development of hypertension in the SHR rats.Dedicated to Professor Yasuzo Tsukada.     

Orexins in rat dorsal motor nucleus of the vagus potently stimulate gastric motor function

Orexins regulate food intake, arousal, and the sleep-wake cycle. They are synthesized by neurons in the lateral hypothalamus and project to autonomic areas in the hindbrain. Orexin A applied to the dorsal surface of the medulla stimulates gastric acid secretion via a vagally mediated pathway. We tested the hypothesis that orexins in the dorsal motor nucleus (DMN) of the vagus regulate gastric motor function. Multibarelled micropipette assemblies were used to administer vehicle, L-glutamate, orexins A (1 and 10 pmol) and B (10 pmol), and a dye marker into this site in anesthetized rats. When the pipette was positioned in the DMN rostral to the obex (where excitation of neurons by L-glutamate evoked an increase in contractility), orexins A and B increased intragastric pressure and antral motility. In contrast, 10 pmol orexin A microinjected into the DMN caudal to the obex (where L-glutamate evokes gastric relaxation through a vagal inhibitory pathway) did not significantly alter gastric motor function. In separate immunocytochemical studies, orexin receptor 1 was highly expressed in neurons in the DMN. Specifically, it was present in retrogradely labeled preganglionic neurons in the DMN that innervate the stomach. These data are consistent with the idea that orexin A stimulates vagal excitatory motor neurons. These are the first data to suggest that orexins in the DMN have potent and long-lasting effects to increase gastric contractility.     

Cholecystokinin octapeptide immunoreactivity in the nucleus tractus solitarius of the cat

The nucleus tractus solitarius possessed distinct patterns of cholecystokinin immunoreactive fibers and cell bodies within its various subdivisions. The commissural, medial, intermediate, parvocellular, dorsolateral and interstitial subdivisions contained relatively dense amounts of CCK immunolabelled fibers. In contrast, CCK immunoreactivity within the ventrolateral subdivision consisted of a few scattered fibers and small neurons. The commissural, intermediate, medial, dorsolateral and parvocellular subdivisions contained CCK immunoreactive neurons following colchicine treatment. The presence of CCK in the NTS suggest that it may be involved as a neuromodulator and/or neurotransmitter in circuitry that mediate cardiovascular, respiratory, gastrointestinal and taste functions.     

Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus

Using whole cell patch-clamp recordings, we investigated the effects of the GABA(B) receptor agonist baclofen in thin slices of rat brain stem containing identified gastric- or intestinal-projecting dorsal motor nucleus of the vagus (DMV) neurons. Perfusion with baclofen (0.1-100 microM) induced a concentration-dependent outward current (EC(50), 3 microM) in 54% of DMV neurons with no apparent differences between gastric- and intestinal-projecting neurons. The outward current was attenuated by pretreatment with the selective GABA(B) antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABA(B) receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, we showed that the outward current was due to effects on potassium and calcium currents as well as calcium-dependent potassium currents. The calcium-mediated components of the outward current were more prominent in intestinal-projecting neurons than in gastric-projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting neurons in the rat DMV, its mechanism of action differs among the neuronal subpopulations.     

神经降压素对迷走运动背核神经元兴奋作用的离体的研究

Intracellular recordings were made from neurons of the dorsal motor nucleus of the vagus (DMV) in rat brain slices. Most of DMV neurons (88%) were depolarized by droplets or perfusion of neurotensin (NT) in a dose-dependent manner. The depolarization, accompanied by an increase in membrane resistance, depended on extracellular K+ concentration and reversed polarity at about -82 mV. Perfusion with Ca(2+)-free/high-Mg2+ solution or with 1 mumol/L TTX solution, which blocked synaptic activities, did not eliminate NT-induced depolarization. The results indicate that NT excites DMV neurons through postsynaptic mechanism and this exciting depolarization may result from a decrease in K+ conductance.     

Substance P binding sites in the nucleus tractus solitarius of the cat

Substance P binding sites in the nucleus tractus solitarius were visualized with receptor autoradiography using Bolton-Hunter [¹²⁵I]substance P. Substance P binding sites were found to have distinct patterns within the cat nucleus tractus solitarius. The majority of substance P binding sites were present in the medial, intermediate and the peripheral rim of the parvocellular subdivisions. Lower amounts of substance P binding sites were present in the commissural, ventrolateral, interstitial and dorsolateral subdivisions. No substance P binding sites were present in the central region of the parvocellular subdivision or the solitary tract. The localization of substance P binding sites in the nucleus tractus solitarius is very similar to the patterns of substance P immunoreactive fibers previously described for this region. Results of this study add further support for a functional role of substance P in synaptic circuits of the nucleus tractus solitarius.     

Retrograde degeneration within the dorsal motor vagal nucleus following bilateral vagotomy in rabbits

The effects of unilateral and bilateral intrathoracic vagotomy on the neuronal structure of the dorsal motor nucleus of the vagus were studied in rabbits. Degeneration affected mainly the small neurones which disintegrated and vanished from dorsal motor nucleus relative to the survival time after operation. A substantial proportion of large neurones was lost or degenerated, but some were preserved unchanged. In unilaterally vagotomized rabbits the dorsal motor nucleus of the intact side showed scattered neurones with axonal reaction which stands up for peripheral crossing of the vagi. The degree of retrograde degeneration was largely determined by the survival time. The nucleus ambiguus was bilaterally preserved unchanged.     

迷走神经背核对胃机能调控的研究进展

神经解剖学和生理学的研究证明,迷走神经背核（dorsal motor nucleus of the vagus,DMV）是调控胃机能的重要副交感初级中枢。支配胃的迷走神经纤维主要发自于延髓的DMV。就DMV的细胞构筑和突触联系、DMV对胃的神经支配、电刺激DMV对胃机能的影响以及DMV内的神经递质和受体对胃机能的调控进行综述。     

Norepinephrine effects on identified neurons of the rat dorsal motor nucleus of the vagus

The dorsal motor nucleus of the vagus (DMV) receives more noradrenergic terminals than any other medullary nucleus; few studies, however, have examined the effects of norepinephrine (NE) on DMV neurons. Using whole cell recordings in thin slices, we determined the effects of NE on identified gastric-projecting DMV neurons. Twenty-five percent of DMV neurons were unresponsive to NE, whereas the remaining 75% responded to NE with either an excitation (49%), an inhibition (26%), or an inhibition followed by an excitation (4%). Antrum/pylorus- and corpus-projecting neurons responded to NE with a similar percentage of excitatory (49 and 59%, respectively) and inhibitory (20% for both groups) responses. A lower percentage of excitatory (37%) and a higher percentage of inhibitory (36%) responses were, however, observed in fundus-projecting neurons. In all groups, pretreatment with prazosin or phenylephrine antagonized or mimicked the NE-induced excitation, respectively. Pretreatment with yohimbine or UK-14304 antagonized or mimicked the NE-induced inhibition, respectively. These data suggest that NE depolarization is mediated by alpha(1)-adrenoceptors, whereas NE hyperpolarization is mediated by alpha(2)-adrenoceptors. In 16 neurons depolarized by NE, amplitude of the action potential afterhyperpolarization (AHP) and its kinetics of decay (tau) were significantly reduced vs. control. No differences were found on the amplitude and tau of AHP in neurons hyperpolarized by NE. Using immunohistochemical techniques, we found that the distribution of tyrosine hydroxylase fibers within the DMV was significantly different within the mediolateral extent of DMV; however, distribution of cells responding to NE did not show a specific pattern of localization.     

Opioids and central baroreflex control: a site of action in the nucleus tractus solitarius

These studies investigated whether the nucleus of the tractus solitarius (NTS) is a central site where opioids modulate baroreceptor reflexes. Microinjections into the NTS of [D-Ala2,MePhe4, Gly-ol5]enkephalin (DAGO) significantly reduced reflex-mediated depressor responses evoked by electrical stimulation of the aortic nerve. Subsequent NTS injections of naloxone restored baroreflexes to control levels. These results demonstrate that the NTS is a central site where exogenously administered opioids can modulate baroreceptor reflexes. NTS injections of naloxone had no effect on baroreflex function, suggesting that tonic activation of opioid receptors at this site plays little or no role in central baroreflex control.     

Electrophysiological study on the effects of leptin in rat dorsal motor nucleus of the vagus

Immunoreactivity of leptin receptor (Ob-R) has been detected in rat dorsal motor nucleus of the vagus (DMNV). Here, we confirmed the presence of Ob-R immunoreactivity on retrograde-labeled parasympathetic preganglionic neurons in the DMNV of neonatal rats. The present study investigated the effects of leptin on DMNV neurons, including parasympathetic preganglionic neurons, by using whole cell patch-clamp recording technique in brain stem slices of neonatal rats. Leptin (30-300 nM) induced membrane depolarization and hyperpolarization, respectively, in 14 and 15 out of 80 DMNV neurons tested. Both leptin-induced inward and outward currents persisted in the presence of TTX, indicating that leptin affected DNMV neurons postsynaptically. The current-voltage (I-V) curve of leptin-induced inward currents is characterized by negative slope conductance and has an average reversal potential of -90 +/- 3 mV. The reversal potential of the leptin-induced inward current was shifted to a more positive potential level in a high-potassium medium. These results indicate that a decrease in potassium conductance is likely the main ionic mechanism underlying the leptin-induced depolarization. On the other hand, the I-V curve of leptin-induced outward currents is characterized by positive slope conductance and has an average reversal potential of -88 +/- 3 mV, suggesting that an increase in potassium conductance may underlie leptin-induced hyperpolarization. Most of the leptin-responsive DMNV neurons were identified as being parasympathetic preganglionic neurons. These results suggest that the DMNV is one of the central target sites of leptin, and leptin can regulate parasympathetic outflow from the DMNV by directly acting on the parasympathetic preganglionic neurons of the DMNV.     

Outline of the arcuate nucleus in the human medulla oblongata.

The outline of the arcuate nucleus in the human medulla oblongata was studied in a series of serial sections of brain stems of newborn and young children. The nucleus lies on the ventral aspect of the pyramid. At higher levels the nucleus lies on the ventral and medial aspect of the pyramid. In the upper regions of the medulla the two nuclei fuse together, giving rise to a median dorsal extension, which in the uppermost part of the medulla extends to the floor of the fourth ventricle. The nucleus sends numerous branches to the corticospinal portion of the pyramidal tract, while the dorsal extension of the arcuate nucleus sends numerous transverse rays on either side which consist of nerve fibres and cells. These rays extend in the areas of the medulla occupied by the medial lemniscus, tectospinal portion, and medial longitudinal bundle. The significance of the findings is discussed.     

Effects of pancreatic polypeptide on pancreas-projecting rat dorsal motor nucleus of the vagus neurons

We investigated the pre- and postsynaptic effects of pancreatic polypeptide (PP) on identified pancreas-projecting neurons of the rat dorsal motor nucleus of the vagus in thin brain stem slices. Perfusion with PP induced a TTX- and apamin-sensitive, concentration-dependent outward (22% of neurons) or inward current (21% of neurons) that was accompanied by a decrease in input resistance; PP was also found to affect the amplitude of the action potential afterhyperpolarization. The remaining 57% of neurons were unaffected. PP induced a concentration-dependent inhibition in amplitude of excitatory (n = 22 of 30 neurons) and inhibitory (n = 13 of 17 neurons) postsynaptic currents evoked by electrical stimulation of the adjacent nucleus of the solitary tract, with an estimated EC(50) of 30 nM for both. The inhibition was accompanied by an alteration in the paired pulse ratio, suggesting a presynaptic site of action. PP also decreased the frequency, but not amplitude, of spontaneous excitatory (n = 6 of 11 neurons) and inhibitory currents (n = 7 of 9 neurons). In five neurons, chemical stimulation of the area postrema (AP) induced a TTX-sensitive inward (n = 3) or biphasic (outward and inward) current (n = 2). Superfusion with PP reversibly reduced the amplitude of these chemically stimulated currents. Regardless of the PP-induced effect, the vast majority of responsive neurons had a multipolar somata morphology with dendrites projecting to areas other than the fourth ventricle or the central canal. These results suggest that pancreas-projecting rat dorsal motor nucleus of the vagus neurons are heterogeneous with respect to their response to PP, which may underlie functional differences in the vagal modulation of pancreatic functions.     

蓝斑核、中缝大核和迷走神经背核在胃运动调节中的关系

目的：探讨蓝斑（LC）、中缝大核（NRM）和迷走神经背核（DMV）,及其相关递质和受体对胃运动的调节途径及机制,阐明它们在调节胃运动中的相互关系。方法：实验采用了核团定位电刺激、损毁和核团微量注射等实验方法,以记录胃内压,统计胃收缩幅度作为胃运动变化的指标。结果：①刺激LC显著降低胃收缩幅度（P〈0.01）,损毁DMV可以减弱此效应,而阻断DMV上的肾上腺素能α受体,可以反转此抑胃效应。②刺激NRM显著降低胃收缩幅度（P〈0.01）,损毁DMV后此效应被消除;阻断DMV上的5-HT2A受体使胃收缩幅度大幅度降低（P〈0.01）,此时再刺激NRM不能进一步的抑制胃运动;而损毁LC后刺激NRM,可消除NRM的抑胃效应,在LC注射5-HT2A受体阻断剂也可以消除该效应。结论：①LC可能通过DMV的5-HT2A受体和α受体对生理条件下正常胃的运动起着重要的双向调节作用;②NRM通过LC上的5-HT2A受体而发挥其对胃运动的抑制效应。