Identification and function of brain stem neurons regulating rat ileal water absorption

The central nervous system (CNS) regions regulating ileal water and ion absorption are unknown. We determined 1) the CNS origin of brain stem neurons that directly innervate the rat ileum, and 2) that these neurons influence intestinal water absorption. Horseradish peroxidase (HRP) was injected into the muscle layer of the rat ileum. The brains were examined for HRP reaction product (HRPRP) 3, 5, or 7 days later. Only cell bodies of the dorsal motor nucleus of the vagus (DMNV) were labeled. Unilateral cervical vagotomy prevented deposition in the ipsilateral DMNV. To determine whether the DMNV regulates ileal water absorption, electrical and chemical stimulation (30 microA, 4 Hz, 0.2 ms, and 300 pmol L-glutamate every 5 min, respectively) were used. Both the DMNV and the adjacent nucleus tractus solitarius (NTS) were stimulated, causing a reduction in water absorption. Bilateral vagotomy prevented the effect of bilateral electrical stimulation, but unilateral vagotomy did not prevent the decrease due to ipsilateral stimulation. These studies show that 1) the DMNV innervates the ileum, and 2) alteration of vagal efferent activity by stimulation of the DMNV and NTS reduces ileal water absorption.

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cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00138.2014 ◽

2014 ◽

Vol 307 (6) ◽

pp. R711-R720 ◽

Cited By ~ 17

Author(s):

Camille B. Blake ◽

Bret N. Smith

Keyword(s):

Brain Stem ◽

Protein Trafficking ◽

Nucleus Tractus Solitarius ◽

Whole Body ◽

Motor Nucleus ◽

Synaptic Inhibition ◽

Diabetic Mice ◽

Dorsal Motor Nucleus ◽

Whole Body Metabolism ◽

Camp Levels

Pathologies in which insulin is dysregulated, including diabetes, can disrupt central vagal circuitry, leading to gastrointestinal and other autonomic dysfunction. Insulin affects whole body metabolism through central mechanisms and is transported into the brain stem dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarius (NTS), which mediate parasympathetic visceral regulation. The NTS receives viscerosensory vagal input and projects heavily to the DMV, which supplies parasympathetic vagal motor output. Normally, insulin inhibits synaptic excitation of DMV neurons, with no effect on synaptic inhibition. Modulation of synaptic inhibition in DMV, however, is often sensitive to cAMP-dependent mechanisms. We hypothesized that an effect of insulin on GABAergic synaptic transmission may be uncovered by elevating resting cAMP levels in GABAergic terminals. We used whole cell patch-clamp recordings in brain stem slices from control and diabetic mice to identify insulin effects on inhibitory neurotransmission in the DMV in the presence of forskolin to elevate cAMP levels. In the presence of forskolin, insulin decreased the frequency of inhibitory postsynaptic currents (IPSCs) and the paired-pulse ratio of evoked IPSCs in DMV neurons from control mice. This effect was blocked by brefeldin-A, a Golgi-disrupting agent, or indinavir, a GLUT4 blocker, indicating that protein trafficking and glucose transport were involved. In streptozotocin-treated, diabetic mice, insulin did not affect IPSCs in DMV neurons in the presence of forskolin. Results suggest an impairment of cAMP-induced insulin effects on GABA release in the DMV, which likely involves disrupted protein trafficking in diabetic mice. These findings provide insight into mechanisms underlying vagal dysregulation associated with diabetes.

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Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00199.2017 ◽

2018 ◽

Vol 314 (2) ◽

pp. R216-R227 ◽

Cited By ~ 7

Author(s):

C. Stryker ◽

D. W. Camperchioli ◽

C. A. Mayer ◽

W. J. Alilain ◽

R. J. Martin ◽

...

Keyword(s):

Extracellular Matrix ◽

Brain Stem ◽

Nucleus Tractus Solitarius ◽

Area Postrema ◽

Brain Maturation ◽

Motor Nucleus ◽

Perineuronal Net ◽

Cardiorespiratory Control ◽

Dorsal Motor Nucleus ◽

Control Regions

The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined 1) whether there is a critical postnatal period of ECM expression in brain stem cardiorespiratory control regions and 2) whether the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia [SH (11% O2, 24 h/day)] exposure is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal motor nucleus, cuneate nucleus, and area postrema were immunofluorescently processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key proteoglycan of the ECM and the perineuronal net. From postnatal day ( P) 5 ( P5), aggrecan and WFA expression increased postnatally in all regions. We observed an abrupt increase in aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, between P10 and P15 followed by a distinct and transient plateau between P15 and P20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (between P10 and P15). SH between P11 and P15 attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, dorsal motor nucleus of the vagus, and area postrema. An intracisternal microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate proteoglycans, rescued the HVR and the increased aggrecan expression. These data indicate that important stages of ECM formation take place in key brain stem respiratory neural control regions and appear to be associated with a heightened vulnerability to hypoxia.

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Postnatal developmental expressions of neurotransmitters and receptors in various brain stem nuclei of rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.01301.2004 ◽

2005 ◽

Vol 98 (4) ◽

pp. 1442-1457 ◽

Cited By ~ 74

Author(s):

Qiuli Liu ◽

Margaret T. T. Wong-Riley

Keyword(s):

Brain Stem ◽

Respiratory Control ◽

Nucleus Ambiguus ◽

Hypoglossal Nucleus ◽

Motor Nucleus ◽

Developmental Trend ◽

Receptor Subunit ◽

Cuneate Nucleus ◽

Glycine Receptors ◽

Dorsal Motor Nucleus

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3–4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-d-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3–4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Bötzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.

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Distribution of vagal cardioinhibitory neurons in the medulla of the cat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1980.238.1.r57 ◽

1980 ◽

Vol 238 (1) ◽

pp. R57-R64 ◽

Cited By ~ 4

Author(s):

J. Ciriello ◽

F. R. Calaresu

Keyword(s):

Nucleus Tractus Solitarius ◽

Border Region ◽

Nucleus Ambiguus ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

Antidromic Stimulation ◽

Low Threshold ◽

Vagal Bradycardia ◽

Medullary Nuclei ◽

Stimulation Of

Experiments were done in cats anesthetized with chloralose, paralyzed and artificially ventilated cats to obtain electrophysiological evidence on the medullary site of origin of vagal cardioinhibitory fibers. The regions of the nucleus ambiguus (AMB), dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarius (NTS), and external cuneate nucleus (ECN) were systematically explored for units responding both to antidromic stimulation of the cardiac branches of the vagus (CBV) and to orthodromic stimulation of the carotid sinus and aortic depressor nerves. Eighty-six single units conforming to these criteria were found in the medulla: 30 in the AMB, 26 in the DMV, 12 in the NTS, 8 in the NTS-DMV border region, and 10 in the ECN. Antidromically evoked spikes had durations of 0.5--2.5 ms and followed stimulation frequencies of 20--500 Hz. The axons of these units conducted at velocities of 3.3--20.8 m/s. The specificity of activation of medullary units by cardioinhibitory fibers was tested in 11 units, which were found to respond consistently with an antidromic spike to stimulation of CBV but not to stimulation of the thoracic vagus. In eight spinal animals low threshold (less than 15 microA) sites eliciting vagal bradycardia were found in the same medullary nuclei where cardioinhibitory units had been located. These results indicate that vagal cardioinhibitory axons, originate in at least three medullary nuclei, the AMB, DMV, and NTS. Unit activity from the ECN may have been recorded from carioinhibitory fibers because of the short duration of the spike potentials.

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Studies of the Central Neural Pathways to the Stomach and Zusanli (ST36)

The American Journal of Chinese Medicine ◽

10.1142/s0192415x01000241 ◽

2001 ◽

Vol 29 (02) ◽

pp. 211-220 ◽

Cited By ~ 27

Author(s):

Chang Hyun Lee ◽

Han Sol Jung ◽

Tae Young Lee ◽

Sang Ryoung Lee ◽

Sang Won Yuk ◽

...

Keyword(s):

Spinal Cord ◽

Vagus Nerve ◽

Nucleus Tractus Solitarius ◽

Area Postrema ◽

Reticular Nucleus ◽

Hypothalamic Nucleus ◽

Cell Group ◽

Motor Nucleus ◽

Amygdaloid Nucleus ◽

Dorsal Motor Nucleus

The purpose of this morphological study was to investigate the relation between the meridian, meridian points and viscera using neuroanatomical tracers. The common locations of the spinal cord and brain projecting to the stomach and Zusanli were observed following injection of CTB (cholera toxin B subunit) and pseudorabies viruses (PRV-Ba, Bartha strain and PRV-Ba-Gal, galactosidase insertion) into the stomach and Zusanli (ST36). After 4–5 days of survival following injection into twelve rats, they were perfused, and their spinal cords and brains were frozen sectioned (30 μm). These sections were stained by X-gal histochemical, CTB and PRV-Bia immunohistochemical staining methods, and examined with the light microscope. The results were as follows: Commonly labeled medulla oblongata regions were dorsal motor nucleus of vagus nerve (DMV), nucleus tractus solitarius (NTS) and area postrema (AP) following injection of CTB and PRV-Ba-Gal into stomach and Zusanli, respectively. In the spinal cord, commonly labeled neurons were found in thoracic, lumbar and sacral spinal segments. Densely labeled areas were found in lamina IV, V, VII (intermediolateral nucleus) and X of the spinal cord. In the brain, commonly labeled neurons were found in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse nucleus, A5 cell group, central gray matter, paraventricular hypothalamic nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed nucleus of stria terminals and amygdaloid nucleus. Thus central autonomic center project both to the stomach and Zusanli. These morphological results suggest that there is a commonality of CNS cell groups in brain controlling stomach (viscera) and Zusanli (limb).

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Strain differences in pH-sensitive K+ channel-expressing cells in chemosensory and nonchemosensory brain stem nuclei

Journal of Applied Physiology ◽

10.1152/japplphysiol.00439.2014 ◽

2014 ◽

Vol 117 (8) ◽

pp. 848-856 ◽

Cited By ~ 3

Author(s):

Paul F. Martino ◽

S. Olesiak ◽

D. Batuuka ◽

D. Riley ◽

S. Neumueller ◽

...

Keyword(s):

Brain Stem ◽

Nucleus Tractus Solitarius ◽

Ph Sensitive ◽

Nucleus Ambiguus ◽

Female Rats ◽

Brown Norway ◽

Motor Nucleus ◽

Male And Female ◽

Male And Female Rats ◽

Bötzinger Complex

The ventilatory CO2 chemoreflex is inherently low in inbred Brown Norway (BN) rats compared with other strains, including inbred Dahl salt-sensitive (SS) rats. Since the brain stem expression of various pH-sensitive ion channels may be determinants of the CO2 chemoreflex, we tested the hypothesis that there would be fewer pH-sensitive K+ channel-expressing cells in BN relative to SS rats within brain stem sites associated with respiratory chemoreception, such as the nucleus tractus solitarius (NTS), but not within the pre-Bötzinger complex region, nucleus ambiguus or the hypoglossal motor nucleus. Medullary sections (25 μm) from adult male and female BN and SS rats were stained with primary antibodies targeting TASK-1, Kv1.4, or Kir2.3 K+ channels, and the total (Nissl-stained) and K+ channel immunoreactive (-ir) cells counted. For both male and female rats, the numbers of K+ channel-ir cells within the NTS were reduced in the BN compared with SS rats ( P < 0.05), despite equal numbers of total NTS cells. In contrast, we found few differences in the numbers of K+ channel-ir cells among the strains within the nucleus ambiguus, hypoglossal motor nucleus, or pre-Bötzinger complex regions in both male and female rats. However, there were no predicted functional mutations in each of the K+ channels studied comparing genomic sequences among these strains. Thus we conclude that the relatively selective reductions in pH-sensitive K+ channel-expressing cells in the NTS of male and female BN rats may contribute to their severely blunted ventilatory CO2 chemoreflex.

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Distribution of α2-Adrenergic Receptor Binding in the Developing Human Brain Stem

Pediatric and Developmental Pathology ◽

10.1007/s100240010138 ◽

2001 ◽

Vol 4 (3) ◽

pp. 222-236 ◽

Cited By ~ 17

Author(s):

Jaleh Mansouri ◽

Ashok Panigrahy ◽

Susan F. Assmann ◽

Hannah C. Kinney

Keyword(s):

Brain Stem ◽

Reticular Formation ◽

Inferior Olive ◽

Human Life ◽

Motor Nucleus ◽

Solitary Tract ◽

Medullary Reticular Formation ◽

Cardiorespiratory Control ◽

Dorsal Motor Nucleus ◽

Early Human

Rapid and dramatic changes occur in cardiorespiratory function during early human life. Catecholamines within select brain stem nuclei are implicated in the control of autonomic and respiratory function, including in the nucleus of the solitary tract and the dorsal motor nucleus of X. Animal and adult human studies have shown high binding to α2-adrenergic receptors in these regions. To determine the developmental profile of brainstem α2-adrenergic binding across early human life, we studied brain stems from five fetuses at mid-gestation, three newborns (37–38 postconceptional weeks), and six infants (44–61 postconceptional weeks). We used quantitative tissue receptor autoradiography with [3H]para-aminoclonidine as the radioligand and phentolamine as the displacer. In the fetal group, binding was high (63–93 fmol/mg tissue) in the nucleus of the solitary tract, dorsal motor nucleus of X, locus coeruleus, and reticular formation; it was low (<32 fmol/mg tissue) in the principal inferior olive and basis pontis. Binding decreased in all regions with age: in infancy, the highest binding was in the intermediate range (32–62 fmol/mg tissue) and was localized to the nucleus of the solitary tract and dorsal motor nucleus of X. The most substantial decrease in binding (75%–85%) between the fetal and infant periods occurred in the pontine and medullary reticular formation and hypoglossal nucleus. Binding remained low in the principal inferior olive and basis pontis. The decreases in binding with age remained significant after quench correction. These data suggest that rapid and dramatic changes occur in early human life in the brain stem catecholaminergic system in regions related to cardiorespiratory control.

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PYY in brain stem nuclei induces vagal stimulation of gastric acid secretion in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.6.g943 ◽

1995 ◽

Vol 268 (6) ◽

pp. G943-G948 ◽

Cited By ~ 1

Author(s):

H. Yang ◽

Y. Tache

Keyword(s):

Acid Secretion ◽

Brain Stem ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Serotonin Receptor ◽

Peptide Yy ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

Raphe Pallidus ◽

Stimulation Of

The influence of peptide YY (PYY) microinjected into brain stem nuclei on gastric acid secretion (GAS) was investigated in urethan-anesthetized rats with gastric cannula. PYY (30-200 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) induces a dose-related and vagal-dependent stimulation of GAS (net increase from 13 +/- 4 to 59 +/- 12 mumol/90 min). PYY (200 ng) injected intravenously intracisternally into sites adjacent to the DMN had no effect. GAS induced by PYY into the DMN was potentiated by coinjection of thyrotropin-releasing hormone (TRH, 30 ng) or the serotonin receptor (5-HT2) agonist (+/-)-1-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (357 ng) and by microinjection of kainic acid (1 ng) into the raphe pallidus. Prepro-TRH-(160-169) (200 ng into the DMN) did not influence the stimulatory effect of PYY. PYY (200 ng) microinjected into the raphe pallidus, raphe obscurus, and nucleus ambiguous also increased GAS, although the response was of shorter duration than that in the DMN. These results indicate that PYY acts in brain stem nuclei involved in the vagal regulation of GAS and that PYY action in the DMN is potentiated by TRH or 5-HT2 receptor agonist acting at this site.

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Inhibitory effect of somatostatin on vagal motoneurons in the rat brain stem in vitro

AJP Cell Physiology ◽

10.1152/ajpcell.1989.256.1.c155 ◽

1989 ◽

Vol 256 (1) ◽

pp. C155-C159 ◽

Cited By ~ 19

Author(s):

J. Nabekura ◽

Y. Mizuno ◽

Y. Oomura

Keyword(s):

Brain Stem ◽

Rat Brain ◽

Reversal Potential ◽

Input Resistance ◽

Inhibitory Effect ◽

Hill Coefficient ◽

Resting Membrane Potential ◽

Motor Nucleus ◽

Dorsal Motor Nucleus

Effects of somatostatin-14 (SRIF) on membrane electrical properties were studied in rat brain stem slice preparations maintained in vitro. SRIF hyperpolarized the resting membrane potential and decreased the input resistance of more than two-thirds of the 85 vagal motoneurons tested in the dorsal motor nucleus of the vagus. These effects persisted under synaptic blockade caused by perfusion with a solution containing tetrodotoxin or a Ca2+-free/high-Mg2+ solution and were dependent on the extracellular SRIF concentration (5 X 10(-8) to 1 X 10(-8) M). The Hill coefficient was estimated to be 2. The reversal potential of SRIF-induced hyperpolarization was affected by changing external K+ concentration. The results suggest that, in addition to its well-known peripheral action, SRIF may inhibit secretomotor functions of visceral organs by reducing vagal output in the central nervous system.

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