Central control of the circulation by the rostral ventrolateral reticular nucleus: anatomical substrates.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D J Reis
Publications and source records attributed to D J Reis.
A glutamate mechanism in the intermediolateral nucleus mediates sympathoexcitatory responses to stimulation of the rostral ventrolateral medulla.
Explore the source record for details and available documents.
Animals↗
Clonidine-displacing substance is present in peripheral tissues of the rat.
Clonidine-displacing substance (CDS) is biologically active in the brain, as well as the gastric fundus, platelets and vas deferens. We sought to determine whether CDS is contained within peripheral tissues in the rat. Using competitive radioimmunoassay with a clonidine-specific antiserum and 3H-p-aminoclonidine rat adrenal gland and gastric fundus were shown to contain significantly greater amounts of CDS-like radioimmunoactivity than the brain; intermediate-to-low activity was present in the heart, small intestine, serum, kidney and liver. Lung and skeletal muscle exhibited near-background levels. CDS may not be unique to the brain, but also may be synthesized and stored in peripheral organs.
Animals↗
Content and in vitro release of endogenous amino acids in the area of the nucleus of the solitary tract of the rat.
We sought to identify amino acid neurotransmitter candidates within the nucleus of the solitary tract in rats. Twenty endogenous amino acids were quantified by reverse-phase HPLC with fluorescence detection (30-fmol limit). Micropunches (1 mm) of the intermediate area of the solitary nucleus were prepared, and the amino acid content determined. Of all the components measured, the putative transmitters Glu, Gly, gamma-aminobutyric acid, taurine, Asp, and Ala appeared in greatest concentrations. Bilateral micropunches superfused in vitro with buffered medium containing 56 mM potassium released Glu, gamma-aminobutyric acid, and Gly in a significant manner (p less than 0.05) compared with basal levels. With Glu, 78% was calcium-dependent and, therefore, presumably from nerve endings; 99% of gamma-aminobutyric acid and 42% of Gly were dependent on calcium. After removal of the nodose ganglion, a bilateral decrease in the calcium-dependent release of Glu and gamma-aminobutyric acid, but not Gly, was observed; decreases were significant ipsilateral to the site of ablation. We conclude that (a) Glu is a transmitter of primary afferents in the nucleus of the solitary tract; (b) glutamatergic afferents may interact with gamma-aminobutyric acid system(s) in this region; (c) Gly also may participate in the mediation and/or modulation of cardiovascular or other visceral reflexes; and (d) amino acid neurotransmission may play an integral role in the neurogenic control of arterial pressure.
Amino Acids↗
Neurons of rostral ventrolateral medulla mediate somatic pressor reflex.
The somatic pressor reflex (SPR) elicited in anesthetized paralyzed rats by electrical stimulation of the sciatic or sural cutaneous afferent nerves produced an increase in arterial pressure ranging from 5 to 40 mmHg. Stimulation of femoral or tibial afferent nerves from muscle produced a depressor response. The SPR was not affected by midpontine transection but was eliminated either by hemisection of the lumbar spinal cord contralateral, but not ipsilateral, to the stimulated nerve or by electrolytic or kainic acid lesion of the contralateral, but not ipsilateral, rostral ventrolateral medulla (RVL). Stimulation of the brachial plexus elicited an SPR that was not eliminated by contralateral lumbar hemisection but was abolished by RVL lesion. RVL lesions consistently overlapped areas containing phenylethanolamine N-methyltransferase-labeled C1 adrenergic neurons. Kainic acid injections into the lateral reticular nucleus (LRN) did not affect the SPR. Neither contralateral nor ipsilateral electrolytic lesions of other autonomic areas including parabrachial nucleus, the nucleus tractus solitarii, the A5 region, or the inferior cerebellar peduncle (output pathway of the LRN) affected the reflex. In axonal transport studies using horseradish peroxidase, afferent terminals of the sciatic nerve were shown to overlap spinoreticular neurons in the dorsal horn retrogradely labeled from tracer injections in the RVL. We conclude that the SPR can be elicited in rats, that it is mediated by spinoreticular afferents traveling in the contralateral spinal cord, and that the C1 adrenergic area of the RVL is a critical region for the integration of the somatic pressor reflex.
Afferent Pathways↗
Reticulospinal vasomotor neurons in the RVL mediate the somatosympathetic reflex.
Sympathoexcitatory neurons in the C1 area of the rostral ventrolateral medulla (RVL) that project to the spinal intermediolateral nucleus play an important role in the maintenance of basal sympathetic tone and in the reflex adjustments of sympathetic activity to internal and external stimuli. We sought to determine whether the sympathetic response to somatic afferent activation, the somatosympathetic reflex, also arises from the excitation of reticulospinal vasomotor neurons in the RVL. In urethan-anesthetized, paralyzed, ventilated rats, single sciatic nerve stimuli evoked an early (latency: 26 ms) and a late (latency: 117 ms) excitation of antidromically identified, RVL-spinal, sympathoexcitatory neurons that paralleled and preceded the biphasic increases in splanchnic nerve activity (peak latencies: 87 and 176 ms). The differences between the respective latencies of the RVL unit responses and those recorded in the splanchnic nerve were comparable to the conduction time in the sympathoexcitatory pathway from the RVL to the splanchnic nerve. Both the threshold intensity and the response amplitude vs. stimulus intensity relationship for the sympathetic response were comparable to those for the A-delta-fiber component of the dorsal root response to sciatic stimulation. We conclude that the rat somatosympathetic reflex consists of an early excitatory component due to the early activation of RVL-spinal sympathoexcitatory neurons with rapidly conducting axons and a later peak that may arise from the late activation of these same neurons as well as the early activation of RVL vasomotor neurons with more slowly conducting spinal axons.
Action Potentials↗
Clonidine-specific antisera recognize an endogenous clonidine-displacing substance in brain.
An endogenous substance in brain, clonidine-displacing substance, binds to the same receptor populations as clonidine and is biologically active. Since receptor binding sites can be modeled by using specific antiligand antibodies, we tested the hypothesis that polyclonal antibodies raised in rat and rabbit against the clonidine analog p-aminoclonidine coupled to hemocyanin would recognize compounds structurally related to clonidine, including clonidine-displacing substance. Binding to anti-p-aminoclonidine antibodies was examined by using a competitive radioimmunoassay with tritiated p-aminoclonidine as the radioligand. Central vasodepressor agents that, like clonidine, are known to bind with high affinity to both imidazole sites and alpha 2-adrenergic receptors in brain inhibited radioligand binding to anti-p-aminoclonidine antibodies. All of these agents contain imidazol(in)e and phenyl ring moieties as part of their chemical structures (e.g., oxymetazoline); a number of other compounds without one or both of these rings failed to cross-react with the antisera. Clonidine-displacing substance, partially purified from bovine brain, also inhibited specific radioligand binding to anti-p-aminoclonidine antibodies. The inhibition was dose dependent and high affinity (IC50, 4 Units). The endogenous substance had no effect on the apparent affinity of the antibodies for the radioligand, but blocked a specific number of binding sites. Immunoprecipitation experiments showed that authentic clonidine-displacing substance, that which displaces tritiated p-aminoclonidine binding to membrane receptors, is recognized by anti-p-aminoclonidine antibodies. We conclude that a unique subset of structural determinants required for ligand interaction with both imidazole and alpha 2-adrenergic receptors is critical for binding to anti-p-aminoclonidine antibodies, and that since clonidine-displacing substance is recognized by highly clonidine-specific antisera, it may also contain these determinants within its structure, namely the imidazol(in)e and phenyl ring systems.
Animals↗
Ultrastructural basis for interactions between central opioids and catecholamines. I. Rostral ventrolateral medulla.
Opioids and some alpha 2-adrenergic agonists are both known for their potent hypotensive actions following local application to the rostral ventrolateral medulla (RVL), in particular the region containing the C1 adrenergic neurons. We sought to determine whether coexistence and/or synaptic interactions might account for the commonality of cardiovascular responses to opioids and catecholamines in the RVL. Dual light and electron microscopic (EM) immunoperoxidase labeling of a rat monoclonal antibody against the opioid peptide Leucine5 (Leu5)-enkephalin and immunoautoradiographic localization of a rabbit antiserum against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) were examined in single sections through the RVL of adult colchicine-pretreated rats. Cross-reactivity of the enkephalin antibody was most intense with Leu5-enkephalin. Methionine5-enkephalin as well as dynorphin A, but not beta-endorphin, were also recognized by the antisera. By light microscopy, the Leu5-enkephalin-like immunoreactivity (LE-LI) was identified by peroxidase reaction product in perikarya and processes. Most of the perikarya containing LE-LI were located dorsolaterally or ventromedially to those showing immunoautoradiographic labeling for TH. However, a few perikarya appeared to contain both LE-LI and TH-immunoreactivity (TH-I) which were difficult to differentiate by light microscopy. By EM, perikarya and dendrites immunoreactive for LE, TH, and both LE and TH were readily distinguishable. Perikarya and dendrites immunoautoradiographically labeled for TH alone were more numerous than those containing LE-LI or TH-I and LE-LI. Axon terminals also were immunolabeled either for one or both reaction products. However, the TH-labeled neurons constituted one of the primary (42% from a total of 118) targets of terminals containing LE-LI. Additionally, some of these terminals containing LE-LI shared a common target with TH-labeled terminals. These common target neurons contained either TH-I or TH-I and LE-LI. In most cases, the identified junctions were symmetric and the terminals with LE-LI (0.4-1.2 microns in diameter) contained either (1) a few small clear vesicles (scv's) and numerous intensely immunoreactive large (100-150 nm) dense-core vesicles (dcv's); or (2) many scv's and from 0-6 dcv's of a somewhat smaller (80-120 nm) diameter. The latter type of terminal was more consistently dually labeled for TH. The remaining terminals containing LE-LI formed synaptic junctions with unlabeled perikarya or dendrites (32%), were in apposition to other unlabeled as well as TH or LE- and TH-containing terminals (4%) or were without recognizable specializations within the plane of section (22%).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
A muscle-derived factor(s) induces expression of a catecholamine phenotype in neurons of cultured rat cerebral cortex.
We sought to determine the source of the signal(s) that promotes expression of the catecholamine (CA) enzyme tyrosine hydroxylase (TH) in cultured neurons of embryonic rat cerebral cortex, a tissue which is not thought to contain CA cells in vivo. Cortical neurons were cultured with their non-neuronal constituents and 48 hr later immunostained for TH. Fibroblasts or glia had no effects, however, blood vessels increased the numbers of TH neurons nearly 4-fold. Coculture with either perinatal aorta, skeletal or cardiac muscle, clonal muscle cell lines 1440 (smooth) and L6 (skeletal), conditioned media from L6 cells, or a soluble extract of L6 cells increased the number of TH neurons up to 20-fold. The induction of TH by muscle extract was (1) dose dependent; (2) paralleled by a proportional increase in the steady-state levels of TH mRNA; (3) greatly reduced by the RNA synthesis inhibitor alpha-amanitin or the protein synthesis inhibitor cycloheximide; and (4) unassociated with change in the survival of neurons in culture. The response was not replicated by treatment with other established neurotrophic substances, including NGF, EGF, FGF, PDGF, neuroleukin, insulin, pyruvate, KCI, adenosine, or inosine. We conclude that muscle contains a potentially novel substance, muscle-derived differentiation factor (MDF) that promotes differentiation but not survival of neurons of cerebral cortex by de novo synthesis of TH mRNA and TH protein. Thus, neurons of the CNS, as in periphery, may undergo phenotypic interconversion in response to biologically derived molecules in their environment.
Animals↗
The C1 area of the rostral ventrolateral medulla oblongata. A critical brainstem region for control of resting and reflex integration of arterial pressure.
A population of neurons localized to a small region of the brain stem reticular formation, the rostral ventrolateral reticular nucleus (RVL), is the principal area of the brainstem regulating resting, reflex, and probably behaviorally coupled control of arterial pressure. The critical area of the RVL reticular nucleus engaged in cardiovascular control surrounds a cluster of adrenergic neurons of the C1 group, and is therefore designated the C1 area. C1 area neurons have a direct and extremely potent synaptic relationship with preganglionic sympathetic neurons of the intermediolateral (IML) nucleus of the spinal cord. Neurons in the C1 area are tonically active and fire in relationship to the cardiac cycle, a rhythm imposed by baroreceptors. They thereby provide the background of excitation to preganglionic neurons to maintain normal resting arterial pressure. Which transmitter released by C1 area neurons produces sympathetic excitation is uncertain, but it may be glutamate. C1 area neurons are critical to the integration of a wide range of cardiovascular reflexes, including the arterial pressure responses to arterial baroreceptor, chemoreceptor, and other cardiopulmonary receptor stimulation, to pain and possibly to exercise, to brain stem ischemia and distortion, and probably to the arterial pressure elevations associated with emotional behavior. The cardiovascular neurons of the C1 area are responsive to the actions of a number of neurotransmitters, many of which are confined to local circuit neurons in the region, including gamma-aminobutyric acid (GABA), catecholamines, acetylcholine, and several opiates. They also appear to be the site of action upon arterial pressure of a number of drugs--including clonidine and possibly the beta-blockers. Neurons of the C1 area of the RVL reticular nucleus, therefore, appear to function as one of the most critical output systems of the brain for regulating arterial pressure in health and sickness.
Animals↗
Evidence for the 5-HT hypothesis of suicide. A review of post-mortem studies.
Although suicide was traditionally considered an extreme response to stress, with the most frequent stress being depressive illness, severity of depression does not distinguish those who commit suicide from non-suicide attempters. A biological role involving the serotonergic system, possibly associated with a genetic risk factor, has been postulated. Low levels of 5-HT and 5-HIAA have been found in post-mortem examinations of brain-stem tissues of suicide victims (levels in cortical tissue were generally normal). An increased number of 5-HT2 receptors was found in the pre-frontal cortex of suicide victims, such upregulation having been demonstrated in induced 5-HT deficiency states; 5-HT1A receptors were also increased. Receptor populations may be altered by chronic psychotropic medication; e.g. 5-HT2 downregulation occurs following administration of antidepressants. There is some indication that the adrenergic system may be involved as well, but this will require further study. Antidepressant drugs may be effective in preventing suicide in patients with non-depressive syndromes who exhibit suicidal behaviour.
Brain↗
Cholinergic regulation of arterial pressure by the C1 area of the rostral ventrolateral medulla.
In anesthetized, paralyzed rats intravenous administration of the acetylcholinesterase inhibitor physostigmine (PHY) (100 micrograms/kg) evoked a dose-related rise in arterial pressure (AP) and heart rate (HR) and an associated increase in sympathetic nerve activity (SNA). The responses to PHY were blocked by electrolytic lesions of, or microinjection of kainic acid into, a specific site in the rostral ventrolateral medulla containing a cluster of neurons immunoreactive for the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase and corresponding to the C1 area of the nucleus reticularis rostroventrolateralis (RVL). The C1 area and its surround contain a heretofore unrecognized network of varicose neuronal processes and perikarya labeled immunocytochemically with a monoclonal antibody to the ACh-synthesizing enzyme, choline acetyltransferase (CAT). PHY increased, by over 3-fold, the spontaneous activity of reticulospinal cardiovascular neurons in the C1 area which excite preganglionic sympathetic neurons in the intermediolateral spinal column. The effects of PHY on AP, SNA, and the discharge of reticulospinal neurons were blocked by systemic administration of the muscarinic antagonist scopolamine. Microinjections within the C1 area of the RVL of scopolamine, the M2-selective muscarinic receptor antagonist AF-DX 116, or the high-affinity choline uptake inhibitor hemicholinium-3 blocked the pressor effects of PHY. The nicotinic antagonist hexamethonium and the M1-selective muscarinic receptor antagonist pirenzepine were without effect. We conclude that (1) the increases in AP, HR, and SNA elicited by the systemic administration of PHY result from the augmented action of ACh released from cholinergic terminals within the C1 area of the RVL; (2) the locally released ACh acts through muscarinic receptors of the M2 subtype within the C1 area to produce excitation of intrinsic reticulospinal sympathoexcitatory neurons, thereby increasing the activity of sympathetic preganglionic neurons and consequently elevating AP and HR; and (3) while the specific function of the cholinergic innervation of the C1 area in cardiovascular regulation is unknown, it may contribute to the tonic regulation of AP.
Animals↗
Catecholaminergic neurons in the ventrolateral medulla and nucleus of the solitary tract in the human.
Catecholaminergic neurons in the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS) are important because of their presumed roles in autonomic regulation, including the tonic and reflex control of arterial pressure, neuroendocrine functions, and the chemosensitivity associated with the ventral medullary surface. However, little is known about the connections of these neurons in the human brain. As a first step in analyzing the functional biochemical anatomy of catecholamine neurons in the human, we used antisera against tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) to localize medullary catecholamine-containing neurons and processes in the VLM and the NTS. Cells staining for TH were located throughout the VLM. Most cells staining for TH and PNMT, which are therefore adrenergic, occurred in an area of the VLM probably corresponding to the rostroventrolateral reticular nucleus. Axons of TH-immunoreactive neurons in the VLM projected (1) dorsally, in a series of parallel transtegmental trajectories, toward the dorsomedial reticular formation, the NTS, and vagal motor nucleus, (2) longitudinally, through the central tegmental field, as fascicles running parallel to the neuraxis, (3) ventrolaterally toward the ventral surface (VS) of the rostral VLM where they appeared to terminate, and (4) medially into the raphe, where they arborized. Similar systems of fibers were labeled for PNMT; the longitudinal bundles of PNMT-labeled axons were limited to the principal tegmental bundle and concentrated dorsally. Fibers containing PNMT were also identified in the medullary raphe, on the medullary ventral surface, and contacting intraparenchymal blood vessels. In the NTS, neurons exhibited immunoreactivity to both TH and PNMT: Four principal subgroups of TH-immunoreactive neurons were seen: a ventral, an intermediate, a medial, and a dorsal group. Perikarya containing PNMT were restricted to the dorsolateral aspect of the NTS. Processes containing TH and PNMT immunoreactivity were identified in the medial and dorsolateral NTS; others appeared to project between the NTS and the VLM and within the solitary tract. The presence of catecholaminergic fibers of the VLM interconnecting with the NTS, raphe, intraparenchymal microvessels, VS, and possibly the spinal cord suggests that the autonomic and chemoreceptor functions attributed to these neurons also may apply to the human.
Adult↗
Neuronal and endothelial sites of acetylcholine synthesis and release associated with microvessels in rat cerebral cortex: ultrastructural and neurochemical studies.
We sought to establish what proportion of the cholinergic innervation of the cerebral cortex (CX) is associated with intraparenchymal blood vessels by using immunocytochemical and neurochemical techniques, and whether [3H]acetylcholine ([3H]ACh) is synthesized and released by elements associated with cortical microvessels (MV). MVs and, for comparison, tissue homogenates were prepared using sucrose gradient/differential ultracentrifugation methods. Efficacy of the separation technique was indicated by the activity of gamma-glutamyltranspeptidase (up to 29.2-fold enrichment), an endothelial cell marker enzyme, in the MV fraction and microscopy. The size of isolated microvessels ranged from 5 to 40 micron (o.d.) with 67.7% of the vessels less than 10 micron and 32.2% between 11 and 40 micron (690 vessels measured from 4 animals). By electron microscopy immunoreactive choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh, was localized to: (a) axons and axon terminals opposed to the basal laminae of capillaries and small arterioles, and (b) capillary endothelial cells. ChAT-labeled elements associated with MVs were most prominent in layers I, III and V of the CX consistent with the local pattern of cholinergic innervation. The absolute amount of ACh synthesized (pmol Ach/100 mg wet wt.) by elements associated with cortical MVs was relatively small (2.3% total cortical homogenate activity). Inhibition of MV ChAT activity to 5% of control by the specific ChAT inhibitor, 4-naphthylvinylpyridine, and HPLC analysis of the product, indicated that authentic ACh was measured. Other tissues similarly synthesized small amounts of ACh relative to the CX, caudate nucleus (CN, 2.4%), cerebellum (CRB, 1.4%) and liver (LIV, 3.9%). Consistent with the known extent of the cholinergic innervation of the tissues examined, the rank order of ChAT associated for both MVs and homogenate were: CN greater than CX much greater than CRB greater than LIV. However, based on the specific activities of ChAT, cortical MVs have the remarkable capacity to synthesize ACh at rates 95% greater than cortical (S1 fraction) homogenate (59.0 +/- 3.5 nmol/mg protein/40 min; n = 7), which is enriched in nerve terminals. Except for LV (+11%), other tissues also had remarkably high ChAT activity in MV (% above corresponding homogenate; P less than 0.05, n = 5): CN (+269) and CRB (+313). Release of [3H]ACh from MVs and, for comparison, nerve terminals were graded to K+ depolarization stimulus (5-55 mM), maximal with 55 mM K+ and Ca2+ dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
Acetylcholine↗
Quantitative distribution of muscarinic receptors and choline acetyltransferase in rat medulla: examination of transmitter-receptor mismatch.
Recent reports have identified discrepancies between the anatomical distribution of transmitters and their receptors, a phenomenon known as transmitter-receptor mismatch. However, quantitative determinations of transmitter activity and receptor density in individual brain regions have not been conducted in parallel. We therefore sought to determine quantitatively the relationship between muscarinic acetylcholine receptor density and the density of cholinergic innervation as reflected by activity of the biosynthetic enzyme for acetylcholine, choline acetyltransferase (ChAT). To assure sampling of equivalent regions using the two methods, an 'electronic micropunch' technique was developed to allow measurement of [3H]quinuclidinyl benzilate ([3H]QNB) binding within the corresponding cylinders of tissue obtained by the micropunch cannula. Nineteen regions of the rat medulla (1 mm diameter, 1 mm height) were studied. The micropunch region containing the gracile nucleus, the area postrema and the choroid plexus of the fourth ventricle contained the highest ChAT activity, but exhibited little [3H]QNB binding to muscarinic receptors. However, among the remaining 18 regions a strong correlation was obtained between uncorrected muscarinic receptor density and ChAT activity within each micropunched region (r = 0.89, n = 18). Correction for autoradiographic efficiency weakened the overall relationship between receptor density and ChAT activity (r = 0.58, n = 18). This was due to a relatively high density of receptors associated with fiber tract regions containing low ChAT activity. The presence of receptors within white matter is ordinarily obscured by high tritium quenching. This is consistent with the hypothesis that a portion of muscarinic receptors are located extrasynaptically and may be present within axons.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Phenylethanolamine N-methyltransferase-containing terminals synapse directly on sympathetic preganglionic neurons in the rat.
The ultrastructural morphology as well as neuronal and glial associations of phenylethanolamine N-methyltransferase (PNMT)-containing terminals in the intermediolateral cell column (IML) of the thoracic spinal cord were examined in the rat utilizing the peroxidase-antiperoxidase (PAP) method. The PNMT-immunoreactive terminals were 0.5-1.4 micron in diameter and contained a few mitochondria, a large population of small clear vesicles and from 1 to 6 large dense-core vesicles. The terminals formed synapses primarily with dendrites. The type of axodendritic association (i.e. symmetric or asymmetric) varied with the size of the dendrite, such that the majority of synapses on large dendrites were symmetric and those on smaller dendrites and dendritic spines were asymmetric. Moreover, most of the synaptic associations of PNMT-containing terminals were with the smaller dendritic processes. Many of the PNMT-labeled terminals, as well as their postsynaptic targets, were closely invested with, or apposed to fibrous astrocytic processes. In a subsequent set of experiments, we combined immunoautoradiographic labeling for PNMT with horseradish peroxidase (HRP) retrograde identification of sympathetic preganglionic neurons (SPNs) in the IML to determine whether or not SPNs receive direct synaptic input from the adrenergic terminals. In these sections, PNMT-containing terminals directly synapsed on the HRP-containing (i.e. retrogradely labeled SPNs) perikarya and dendrites. The axosomatic synapses observed between PNMT-labeled terminals and SPN perikarya were exclusively symmetric; whereas the type of axodendritic association varied depending upon the size of the dendrite such that the majority were asymmetric. The findings provide ultrastructural evidence that in the rat IML, adrenergic (i.e. PNMT-containing) terminals (1) may be either excitatory (asymmetric) or inhibitory (symmetric) depending on their site of termination and (2) can influence sympathetic nerve discharge through a direct effect on the SPN cell membrane.
Animals↗
Ultrastructural characterization of substance P-like immunoreactive neurons in the rostral ventrolateral medulla in relation to neurons containing catecholamine-synthesizing enzymes.
Substance P (SP) and catecholamines, particularly adrenaline, have been implicated in cardiovascular responses mediated by neurons in the rostral ventrolateral medulla (RVL). Immunoperoxidase labeling of an antiserum against SP and/or immunoautoradiographic localization of catecholamine (tyrosine hydroxylase-TH)- or adrenaline (phenylethanolamine N-methyltransferase-PNMT)-synthesizing enzymes were examined histologically to determine the cellular basis for a functional interaction involving either synaptic or intracellular relations between these putative transmitters in the adult rat RVL. Peroxidase labeling for SP was localized in perikarya, dendrites, and axon terminals. Most of these perikarya were located medial and ventral to those labeled with TH or PNMT within the same section. However, as others have previously demonstrated by light microscopy, colocalization of SP-like immunoreactivity (SPLI) and PNMT was seen in a few perikarya of colchicine treated animals. Both single- and dual-labeled perikarya contained abundant dense core vesicles. The terminals with SPLI were 0.4-1.4 micron in diameter and contained a few mitochondria, a large population of small, clear vesicles, and from three to 11 large dense core vesicles. In some cases the terminals were seen in continuity with more proximal processes of neurons in the RVL. These terminals formed synapses with a few perikarya and many dendrites, some of which also contained SPLI. In the material dually labeled for TH and SP, terminals with SPLI (n = 32) formed synaptic junctions primarily with TH-labeled dendrites (69%); the remainder were with TH-labeled perikarya (6%) or with unlabeled dendrites (25%). The axosomatic junctions were exclusively symmetric, whereas the majority of axodendritic junctions were primarily asymmetric on small dendrites (0.8-1.0 micron in diameter) or dendritic spines. In sections dually labeled for PNMT and SP, the terminals containing SPLI (n = 37) formed synaptic associations with PNMT-labeled perikarya (11%), PNMT-immunoreactive dendrites (59%), or with perikarya and dendrites lacking PNMT immunoreactivity (30%). The axosomatic junctions were all symmetric and most often associated with the spinous portion of the soma. The axodendritic junctions were primarily asymmetric and were found both on the spinous portion of the PNMT-labeled dendrites. In addition, both TH- and PNMT-labeled somata and dendrites received symmetric and asymmetric contacts from terminals lacking SPLI.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
A high density of muscarinic receptors in the rostral ventrolateral medulla of the rat is revealed by correction for autoradiographic efficiency.
Previous reports of a low density of muscarinic receptors in the vicinity of the rostral ventrolateral reticular nucleus (RVL) conflict with the presence of a muscarinic cholinergic mechanism regulating arterial pressure, and may reflect low autoradiographic efficiency due to quenching of tritium emissions by white matter. Regional autoradiographic efficiency was determined using brains uniformly labeled with O-[3H]methylglucose. Within the RVL, autoradiographic efficiency was only 50 +/- 2% relative to gray matter. The uncorrected density of muscarinic receptors (M2) labeled by [3H]quinuclidinyl benzilate in the RVL appeared to be low relative to cranial nerve nuclei, but the corrected muscarinic receptor density approximated that within the nucleus tractus solitarii. We conclude that a high density of M2 muscarinic acetylcholine receptors is present in the RVL.
Animals↗