Dexfenfluramine and neurotoxicity.
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Animals↗
Biomedical subjects
M Kalia
Publications and source records attributed to M Kalia.
Early ontogeny of the vagus nerve: an analysis of the medulla oblongata and cervical spinal cord of the postnatal rat.
Retrograde transport of cholera toxin conjugated with horseradish peroxidase in the postnatal rat has revealed remarkable features of dendritic fields of vagal motor neurons in the medulla oblongata and cervical spinal cord during the period of early development (0-10 days). At birth, vagal motor neurons in the dorsal motor nucleus of the vagus, nucleus ambiguus, nucleus retroambigualis, nucleus dorsomedials and the spinal nucleus of the accessory nerve are small with relatively few, unbranched processes. The span of the dendritic tree is much smaller than that found in adult animals. By the postnatal Day 2 there are marked changes in the soma as well as in the dendritic tree of these neurons. There is dispersion of the cell bodies within the neuropil as well as an expansion of the total area of the brain stem occupied by these motor neurons and their dendritic processes which show extensive growth and branching. By postnatal Day 3 the most extensive proliferation of these neurons is seen and appears to represent the peak of dendritic growth of vagal motor neurons such that the area occupied by the dendritic tree of a single neuron is three times that seen in an adult rat. This proliferation gradually decreased during the subsequent seven days of early development (i.e. Days 4-10) so that by Day 10 the dendritic span of vagal motor neurons was reduced to about twice the adult size. This growth progressively decreased from Days 10 to 30 at which time adult levels were reached. Ultrastructural examination of these horseradish peroxidase labeled dendrites showed a positive correlation between the number of dendritic processes and the number of axo-dendritic synapses. This was accompanied by an increase in the number of identifiable synaptic junctions. These morphological complexities observed during the period of early development of vagal motor neurons indicate that the vagus nerve undergoes dramatic changes during the period of early development including the establishment of numerous synaptic contacts between vagal afferents and efferents in the brainstem. A number of these changes occur in developing dendritic fields of vagal motor neurons during the first three days of neonatal life. It is reasonable to assume that developmental abnormalities during this "critical period" could produce significant functional changes in the pattern of respiration as well as in the control of airway smooth muscle.
Aging↗
Reversible, short-lasting, and dose-dependent effect of (+)-fenfluramine on neocortical serotonergic axons.
Dextrofenfluramine [+)-fenfluramine) is the dextro-optical isomer of the racemic compound (+/-)-fenfluramine. This compound stimulates the release of serotonin (5-HT) and blocks its re-uptake in serotonergic nerve terminals. (+)-Fenfluramine and its nor metabolite which have been localized in significant amounts in the rat brain are useful anorectic agents in animals. In humans, (+)-fenfluramine is used as an anti-obesity agent when administered orally in doses of 0.25 mg/kg/twice a day. Studies in some animal species (such as the rat and monkey, but not mice) using high doses of (+)-fenfluramine (administered subcutaneously) have shown long-term neurochemical and immunocytochemical effects in selected brain regions. In the present study we used the rat to determine the mechanism underlying the anorectic effect of orally administered (+)-fenfluramine. The rat was selected because long-term effects of (+)-fenfluramine have been previously described in this species. In addition, a variety of other aspects of orally administered (+)-fenfluramine have been addressed in this study. For example, how long does the depletion of 5-HT in the nerve terminals last following cessation of the drug treatment? i.e. is the effect reversible? Is this depletion of 5-HT and the resultant abnormal morphology of 5-HT-immunoreactive nerve terminals seen at high doses dose-dependent? Since some of these questions relate to morphological evaluation of this drug in brain 5-HT systems, we have examined this system as part of our ongoing effort to examine brain monoaminergic systems under perturbed conditions. We have used a morphological (immunocytochemical) approach to answer these questions. The primary function of this study was to evaluate the effects of short-term exposure (4 days) to varying doses of orally administered (+)-fenfluramine on 5-HT-immunoreactive nerve terminals in the frontal cortex of the rat. The frontal cortex was selected because it contains a homogeneous population of nerve fibers and terminals unlike other cortical regions, the hippocampus, striatum and the hypothalamus where a mixed population of coarse and fine fibers has been described. Since the previously reported effect of fenfluramine on 5-HT nerve terminals was the appearance of coarse fibers, the region of cortex selected for this study showed no coarse fibers in the pair-fed control. This essential feature of control regions has not been used in previous studies on this subject. The present study demonstrates that (+)-fenfluramine produces a dose-dependent reduction in 5-HT immunoreactivity of 5-HT nerve terminals in the neocortex of adult rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Centrally administered endothelin-1 produces apnoea in the alpha-chloralose-anaesthetized male rat.
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Animals↗
Comparative evaluation of oral prostaglandin E2 & intravenous oxytocin for induction of labour.
Oral prostaglandin E2 tablets (group I) and iv Oxytocin (group II) were evaluated in 120 randomly selected women subjected to induction of labour. In group I, 60 women received oral prostaglandin E2 tablets in incremental doses from 0.5-1.5 mg hourly, depending upon the parity and Bishop score of the patient. Group II women received oxytocin iv in 5 per cent dextrose, starting at a rate of 2 mU/min and gradually increasing to a maximum of 64 mU/min. Overall success rate in group I (prostaglandin E2) and group II (intravenous oxytocin) was 85 and 93.3 per cent respectively (P greater than 0.05). In the favourable group (Bishop score 6-13) the induction delivery interval (IDI) for group I and group II was 8.86 h and 7.95 h respectively (P greater than 0.05), while in the unfavourable group (Bishop score less than or equal to 5), the IDI for the respective groups were 13.42 h and 10.11 h (P less than 0.05). Side effects with prostaglandin E2 were mostly mild gastrointestinal ones. A significantly higher incidence of foetal distress was observed with intravenous oxytocin (15%) as compared to prostaglandin E2 (3.33%). Oral prostaglandin E2 was thus found to be a better alternative to intravenous oxytocin in multiparous women with favourable Bishop score (greater than 6) and in those in whom fluid retention is to be avoided (e.g., conditions like toxemias, renal disease).
Administration, Oral↗
Rapidly adapting pulmonary receptor afferents: I. Arborization in the nucleus of the tractus solitarius.
The organization of axon collaterals, preterminal processes, and presumptive synaptic boutons of single physiologically identified rapidly adapting receptor (RAR) pulmonary afferent fibers was examined following the intraaxonal application of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). The RAR axons were injected 200-300 microns lateral to the nucleus of the tractus solitarius (nTS) at a number of different rostrocaudal levels in seven individual experiments. The trajectories of the stained axons were reconstructed from individual 50-microns-thick serial sections. The rostrocaudal extent, as well as the distribution of the trajectory of each RAR afferent, was reconstructed from every section by using a camera lucida attachment. In this first of two papers, we describe the pattern of organization of bouton terminals of RAR afferents related to cytoarchitectonically distinct subnuclei of the nTS. In the companion paper, morphological details of the fine structure of these synaptic boutons and axonal branches are described in different subnuclei in order to illustrate morphological differences in these functionally distinct regions. A number of significant findings have resulted from this light microscopic study. The central process of a single RAR afferent fiber arborized in the medulla oblongata over a considerable distance in the rostrocaudal plane (2.5 mm rostral to 1.4 mm caudal to the obex). A single RAR afferent fiber terminated in numerous bouton terminals (range 500-1,050), and these terminals arose from over 400 segments of branches of the parent injected axon. A small number of en passant bouton terminals were found. There appeared to be a remarkable degree of consistency in the subnuclei of the nTS where these terminals arborized. The dorsal and dorsolateral subnuclei of the nTS received 144-647 bouton terminals. The second-largest concentration of bouton terminals of RAR afferents was found in the intermediate (nI) subnucleus of the nTS. No labeled bouton terminal was found in the ventral and ventrolateral subnuclei of the nTS. This finding is in sharp contrast to the terminations of SAR afferents which terminated predominantly in the ventral and ventrolateral nuclei of the nTS, the interstitial nucleus of the nTS, and the nI. The parent RAR axon could be traced as far rostrally as 2.5 mm, even though the region of terminal arborization could not be followed beyond 0.8 mm. The destination of this rostrally projecting RAR afferent could not be determined in this study.(ABSTRACT TRUNCATED AT 400 WORDS)
Action Potentials↗
Rapidly adapting pulmonary receptor afferents: II. Fine structure and synaptic organization of central terminal processes in the nucleus of the tractus solitarius.
The nucleus of the tractus solitarius (nTS) is a site for termination of primary afferents originating from a variety of different visceral sensory endings (Kalia and Mesulam: J. Comp. Neurol. 193:523-553, '80). The light and electron microscopic evaluation of bouton terminals of slowly adapting lung stretch (SAR) afferent fibers originating from the tracheobronchial tree has been described previously (Kalia and Richter: J. Comp. Neurol. 241:503-520, 521-535, '85). The companion article (Kalia and Richter: J. Comp. Neurol. 273:000-000, '88) describes details of the light microscopic organization of a second group of pulmonary afferents, the rapidly adapting receptors (RARs), that are known to signal transient volume changes in airways (Sellick and Widdicombe: J. Physiol. (Lond.) 203: 359-381, '69; Q.J. Exp. Physiol. 55:153-163, '70). Terminals from RAR afferents are concentrated within two specific subnuclear groups of the nTS (dnTS and nI) and are distributed over 4 mm of the medulla oblongata rostrocaudally. Within the nTS, axon collaterals of RAR afferents remain myelinated up to a diameter of 0.4-1.0 microns. Preterminal processes are always unmyelinated and range in diameter from 0.15 to 0.3 microns. Bouton terminals (1.0-2.0 microns) are of both the en passant and end terminal varieties. The synaptic profiles formed by 143 bouton terminals of RAR afferents, were examined in uninterrupted sequential sections and are described in this paper. All the bouton terminals examined under the electron microscope were found to contain clear, round synaptic vesicles. Boutons made synaptic contact with different profiles in each of the two subnuclei (dnTS and nI) examined. Contacts were usually asymmetrical (type I) containing clear, round synaptic vesicles 35-50 nm in diameter. In the dorsal subnucleus of the nTS (dnTS), the synaptic arrangement of RAR boutons did not appear to be complex. The RAR bouton terminal was usually located in juxtaposition to unlabeled axon terminals of similar morphological characteristics. Typically, the RAR bouton terminal made synaptic contact with a medium-sized spiny dendrite. No axosomatic contacts involving RAR afferents were observed in this subnucleus. In the intermediate subnucleus of the nTS (nI), the most common synaptic arrangement of RAR bouton terminals was in the form of a "glomerulus," which was formed by five to seven different types of neuronal profiles surrounding the labeled RAR bouton terminal.(ABSTRACT TRUNCATED AT 400 WORDS)
Afferent Pathways↗
Neuropeptide Y-immunoreactive perikarya and nerve terminals in the rat medulla oblongata: relationship to cytoarchitecture and catecholaminergic cell groups.
The aim of this study was to examine details of the distribution of neuropeptide Y (NPY)-immunoreactive perikarya and nerve terminals in the medulla oblongata in relation to cytoarchitectonically and functionally distinct catecholaminergic regions. The immunoperoxidase method was combined with Nissl staining to determine nuclear boundaries of transmitter-identified nerve cell bodies and to examine the relationship between populations of NPY-immunoreactive neurons and catecholaminergic cell groups (A1, A2, C1, C2, and C3) in serial sections. Previous studies using immunofluorescence have described the existence of NPY catecholaminergic immunoreactive nerve cell bodies in the brainstem. No information is currently available with regard to details of the distribution of these peptidergic neurons and nerve terminals in the functional subnuclear units of the medulla oblongata. In this study we have delineated the anatomical association of NPY immunoreactivity with cardiovascular function. Neuropeptide Y-immunoreactive neurons were found located in close association with noradrenergic neurons of the A1 cell group in the caudal ventrolateral medulla oblongata, where they were usually found located dorsal to the lateral reticular nucleus (LRt). A second population of NPY-immunoreactive neurons was found located medial to the A1 cell group in the ventral subdivision of the reticular nucleus of the medulla (MdV). Neuropeptide Y-immunoreactive neurons in the rostral medulla were found located in regions corresponding to the principal distribution of adrenergic neurons in the C1, C2, and C3 cell groups. In the dorsomedial medulla (A2 region) NPY-immunoreactive neurons were localized in the area postrema (ap) and in a number of subnuclei of the nucleus of the tractus solitarius (nTS), i.e., the dorsal parasolitary region (dPSR), the dorsal strip (ds), the periventricular region (PVR), and the ventral parasolitary region (vPSR). The location of NPY-immunoreactive perikarya and nerve terminals in the dorsal subnuclei of the nTS, i.e., the dPSR and ds, is of particular significance, since this distribution corresponds with the location of small adrenergic neurons as well as with the site of termination of aortic and carotid sinus nerve afferent fibers. NPY-immunoreactive neurons in the dorsomedial medulla are ideally situated for receiving monosynaptic input from baroreceptor afferents and could play a key role in the central integration of cardiovascular reflexes.
Adrenergic Fibers↗
Evidence for discrete alterations in central cardiovascular catecholamine and neuropeptide Y immunoreactive neurons in aged male rats and in genetically hypertensive male rats of the Lyon strain.
A computer-assisted morphometrical and microdensitometrical analysis has been performed on cardiovascular noradrenaline (NA), adrenaline (A) and neuropeptide (Y (NPY) neurons in adult and 24-month-old male rats and on hypotensive (LL), normotensive (LN) and hypertensive (LH) male rats of the Lyon strain using the indirect immunoperoxidase procedures. It was found that in NPY/phenylethanolamine-N-methyltransferase (PNMT) costoring neurons of the CI area of the rostral medulla oblongata NPY-like immunoreactivity showed a more marked reduction than the PNMT immunoreactivity. Furthermore, within the parvocellular part of the paraventricular hypothalamic nucleus. NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis. Thus, in the NPY/PNMT costoring neurons of the A C1 group of the ventrolateral medulla projecting, for example, to the hypothalamus, the peptide transmission line may have a special vulnerability to the aging processes which may contribute to the development of hypertension in old people in view of a vasodepressor role of many central NPY/PNMT neurons. An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed. In a comparison between LL and LH rats the A2 cell group of the LH strain showed a trend for an increase in the mean tyrosine hydroxylase (TH) immunoreactive cell body area and the C3 group showed a significant increase in the number of PNMT immunoreactive profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Central glucocorticoid receptor immunoreactive neurons: new insights into the endocrine regulation of the brain.
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Adrenalectomy↗
Central catecholamine-neuropeptide Y interactions at the pre- and postsynaptic level in cardiovascular centers.
Central catecholamine (CA)-neuropeptide Y (NPY) interactions and their regulation by glucocorticoids have been analyzed in vivo and in vitro, especially in the dorsal cardiovascular center of the medulla oblongata, including the nucleus tractus solitarius (nTS), using immunocytochemical, receptor autoradiographical, biochemical, and physiological techniques. Intraventricular (i.v.t.) injections of NPY in a low (7.5 pmol) or a high (1.25 nmol) dose increased adrenaline levels 4 h later in the caudal part of the dorsomedial medulla. Furthermore, NPY immunoreactivity (IR) tended to decrease in the rostral part of the dorsomedial medulla 5 min after injection of clonidine (1 microgram) in the alpha-chloralose anaesthetized rat. Thus, presynaptic interaction between NPY and adrenaline (A) mechanisms may exist in the dorsal cardiovascular center taking place at the network local circuit level or the membrane level of the NPY/A costoring synapses of the dorsomedial medulla. In vitro NPY (10 nM) reduced the affinity of the alpha 2-adrenergic agonist binding sites in the nTS, and clonidine (10 nM) reduced the 125I-NPY binding in the dorsomedial medulla. These results indicate the existence of postsynaptic receptor-receptor interactions between alpha 2-adrenergic and NPY receptors in the dorsal cardiovascular center. This interaction may in part take place at the level of the Ni protein, since NPY (300 nM) inhibited cyclic AMP (cAMP) accumulation in slices of the dorsomedial medulla. However, the interactions also probably take place at the proteins carrying the recognition sites, since NPY and adrenaline together given i.v.t. significantly antagonized the hypotensive effects of one another. Thus, the reduced affinity of the alpha 2-adrenergic receptor induced by NPY may reflect a reduced efficiency of this receptor and not an increased coupling of Ni protein to the adenylate cyclase. Thus, the postsynaptic interaction between the two receptors represents inter alia a sensitivity regulation of the two receptors. Evidence is also presented for the existence of a glucocorticoid regulation of NPY IR neurons, especially of those innervating the locus coeruleus, since after 2 weeks adrenalectomy reduced NPY IR in this area. Furthermore, glucocorticoid receptor IR was demonstrated in the nuclei of NPY nerve cell bodies of the nTS. Thus, glucocorticoids exert direct actions on cardiovascular NPY/CA costoring neurons, actions that may contribute to their hypertensive effects in humans.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Ganglioside-induced regeneration and reestablishment of axonal continuity in spinal cord-transected rats.
In this study we examined the effect of chronic GM-1 ganglioside treatment on the reestablishment of axonal continuity and functional recovery in spinal cord-transected rats. Previous studies have shown that chronic treatment with GM-1 ganglioside is effective in producing regeneration of lesioned mesostriatal dopaminergic neurons in the central nervous system [1, 2]. In addition, GM-1 ganglioside advances peripheral nerve regeneration following nerve crush injury [12]. Axonal continuity was determined by the ability of the spinal cord to transport horseradish peroxidase across the region of transection. Comparisons between ganglioside-treated and saline-treated controls showed that ganglioside treatment resulted in the reestablishment of axonal continuity between the spinal cord distal to the level of the transection and the brainstem. Saline-treated controls showed little evidence of axonal continuity between these two regions. Thus gangliosides induce reestablishment of axonal continuity and thereby could advance functional recovery in rats following spinal cord transection.
Animals↗
Studies on peptide comodulator transmission. New perspective on the treatment of disorders of the central nervous system.
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Animals↗
Morphology of physiologically identified slowly adapting lung stretch receptor afferents stained with intra-axonal horseradish peroxidase in the nucleus of the tractus solitarius of the cat. I. A light microscopic analysis.
The present series of experiments was designed to study the organization of preterminal processes and synaptic boutons of single physiologically identified slowly adapting receptor (SAR) pulmonary stretch afferent fibers. Intra-axonally injected horseradish peroxidase-wheat germ agglutinin (HRP-WGA) conjugate was used as the label. In the first paper, we describe the pattern of arborization of axon collaterals from single physiologically identified SAR afferent fibers evident in the various subnuclei of the nucleus of the tractus solitarius (nTS). In the second paper, details are presented regarding the ultrastructure of these synaptic boutons and axon collaterals. A number of significant findings resulted from this study: (1) A single lung stretch SAR afferent fiber arborized over a considerable distance rostrocaudally in the brain stem (1,700-2,100 microns). (2) A single lung stretch SAR afferent fiber terminated as hundreds of bouton terminals (650-1,180). (3) There was a remarkable consistency in the subnuclei of the nTS that received these terminal arborizations of SAR afferents. (4) The ventral (vnTS), intermediate (nI), ventrolateral (vlnTS), and interstitial (ni) subnuclei of the nTS were the only regions of the nTS receiving bouton terminals of SAR afferent fibers. (5) Under the light microscope the pattern of termination of SAR afferents was similar in all the axons studied in this series. (6) The injected parent axon in each case could be followed in the TS at all levels and remained consistent with regard to position and orientation and could be traced rostrally to levels as far as 3.5 mm rostral to the obex whereas the region of terminal arborization was located around 1.7-2.1 mm rostral to the obex. This pattern indicates that a single lung stretch SAR afferent fiber descends caudally upon entering the nTS. In the cat vagal afferent fibers are known to enter the medulla at levels between 0.5 mm and 3.2 mm rostral to the obex (Kalia and Mesulam, '80a). The results of the light microscopic analysis presented in this article indicate that lung stretch (SAR) afferents from the lungs and tracheobronchial tree have distinctly localized patterns of distribution in the nTS. In addition, these findings support the concept that representation of pulmonary afferents in the medulla is constituted by a differentiated distribution of nerve terminals in the various subnuclei of the nTS. Modality-specific localization (SAR afferents in this case) appears to be predominant in the nTS. The widespread rostrocaudal distribution of the terminal field of a single lung stretch SAR afferent is remarkable.(ABSTRACT TRUNCATED AT 400 WORDS)
Adaptation, Physiological↗
Morphology of physiologically identified slowly adapting lung stretch receptor afferents stained with intra-axonal horseradish peroxidase in the nucleus of the tractus solitarius of the cat. II. An ultrastructural analysis.
The nucleus of the tractus solitarius is a site for termination of primary afferents originating from a variety of visceral receptors. The localization of bouton terminals of slowly adapting lung stretch (SAR) afferent fibers originating from the tracheobronchial tree have been described in the companion paper (Kalia and Richter, '85). The most conspicuous finding regarding the location of SAR terminals is that they are concentrated within specific subnuclear groups of the nucleus of the tractus solitarius (nTS) and are distributed widely in the rostrocaudal plane of the medulla oblongata. These light microscopic features have provided us with valuable information with regard to the organization of visceral afferents in the central nervous system. The synaptic profiles formed by the 476 bouton terminals of these HRP-labeled afferents have been described in this paper in serial thin sections. All of the bouton terminals examined under the electron microscope were found to contain round synaptic vesicles. Synaptic boutons (1.0-3.0 microns in diameter) were usually of the en passant variety and made contact with different structures depending upon the subnucleus which was examined. In the ventral (v) and the ventrolateral (vl) subnuclei of the nTS, asymmetrical (type I) synaptic contacts containing round, clear synaptic vesicles of 35-50 microns in diameter were found and these contacts were made with (1) the soma of cell bodies located in that subnucleus; (2) spiny dendrites in that nucleus; (3) vesicle-containing axon terminals that were presynaptic to the HRP-labeled bouton terminal; and (4) vesicle-containing dendrites in which the HRP profile was presynaptically located. The terminal axon remained myelinated till the last 1 micron before the bouton terminal was formed. There was no distinct, unmyelinated portion of the terminal axon. The synaptic bouton received axon-axonal synapses from unlabeled bouton terminals containing round, clear vesicles. This is the first report of the localization of these afferent fibers as well as of the regional variations in the ultrastructure of boutons of physiologically identified terminals. It appears likely that the lung stretch afferent fibers, by having axon-axonal as well as axon-somatic contact in the ventral, ventrolateral, and intermediate subnuclei of the nTS, can interact in a variety of different ways in this region. The significance of these features in relation to the precise influence of respiratory afferents on central respiratory mechanisms needs to be evaluated further.
Afferent Pathways↗
Rat medulla oblongata. I. Cytoarchitectonic considerations.
The goal of this study was to define the detailed cytoarchitecture of the medulla oblongata of the rat in order to accurately localize immunocytochemically distinct populations of neurons in this region. The cytoarchitectonic features of this region of the rat brain stem were examined in 40 micron thick serial sections of celloidin embedded brains blocked in the Horsley-Clarke stereotaxic plane. These sections were stained with cresyl violet and examined at a number of different magnifications with a variety of different intensities of staining to demonstrate particular features of the cells in this region. High magnification photomicrographs of this material revealed characteristic features of the various populations of cells. The results illustrate that the cytoarchitecture of the medulla oblongata of the rat changes remarkably within very short distances in the rostrocaudal direction. These changes indicate the need to study the anatomy and immunocytochemistry of this region in detailed serial sections. The ventral reticular formation of the rat medulla is cytoarchitectonically complex. Nuclear groups such as the lateral reticular nucleus (LRt) contain a number of cytoarchitectonically distinct subnuclei, as does the dorsally located nucleus of the tractus solitarious (nTS) (Kalia and Sullivan, '82). These nuclei occupy a considerable length of the medulla and terminate abruptly at the pontomedullary boundary. A number of other cytoarchitectonic features of the medulla were examined and the detailed characteristics were defined.
Animals↗
Rat medulla oblongata. II. Dopaminergic, noradrenergic (A1 and A2) and adrenergic neurons, nerve fibers, and presumptive terminal processes.
The aim of this study was to determine the anatomical relationships between catecholaminergic neurons and cytoarchitectonically defined nuclei in the caudal medulla oblongata. Previous studies have demonstrated the existence of noradrenergic cell bodies (designated as the A1 and A2 cell groups) in the caudal medulla oblongata of the rat (Dahlström and Fuxe, '64), including the nTS. There is no information currently available with regard to details of the distribution of these noradrenergic neurons in the functionally distinct subnuclei of the medulla oblongata. In this study the location of catecholamine-synthesizing enzymes was examined in the serial sections of the caudal medulla oblongata of the rat: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyl transferase (PNMT). The immunoperoxidase method of Sternberger ('79) was used to demonstrate the location of immunoreactive neurons, nerve fibers, and presumptive terminal processes. This was followed by Nissl staining of the same sections to localize accurately the immunoreactivity. Noradrenergic neurons (TH- and DBH-positive and PNMT-negative) were localized in a number of subnuclei of the nucleus of the tractus solitarius (nTS), the area postrema (ap), and in the dorsal motor nucleus of the vagus (dmnX). The distribution of these noradrenergic cells was different at different rostrocaudal levels. In addition, adrenergic neurons (TH-, DBH-, and PMNT-positive) were identified dorsal to the tractus solitarius (TS), in the dorsal strip region (ds), the periventricular region (PVR), the dorsal parasolitarius region (dPSR), and the dmnX (rostral to obex). In addition, dopaminergic neurons (TH-positive and DBH- and PNMT-negative) were found in the ap and dmnX. The A1 cell group in the ventrolateral medulla consisted almost exclusively of noradrenergic neurons (TH- and DBH-positive and PNMT-negative). These results indicate that in the rat the A2 cell group is a mixed population of catecholaminergic neurons that are localized in well-defined regions of the dorsal medulla oblongata. The distribution of these neurons is very specific both in terms of rostrocaudal levels and cytoarchitectonic subdivisions of regions of the medulla known to be involved in central autonomic control. This supports the hypothesis that monoaminergic neurons in the dorsal medulla play important roles in the central regulation of visceral function.
Adrenergic Fibers↗
Rat medulla oblongata. III. Adrenergic (C1 and C2) neurons, nerve fibers and presumptive terminal processes.
The goal of this study was to define the cytoarchitectonic relationships between the catecholaminergic cell groups (the C1 and C2) in the rostral medulla oblongata of the rat. Immunocytochemistry was combined with Nissl staining to determine the nuclear boundaries in this region of the brain stem. In addition, the morphological characteristics of neurons in the C1 and C2 cell groups were determined and the relationship between these populations of neurons and their caudaul counterparts (A1 and A2 cell groups) was established (Kalia et al., '85a). The results indicate that the C1 and C2 cell groups are distributed over a wide region of the rostral medulla. The location of these adrenergic neurons is related to a number of nuclear groups in this region. This finding was remarkably consistent in all the animals studied in this series. In addition, adrenergic nerve fibers were found to be distributed over a large region of the medullary reticular formation. There was homogeneity in the morphology of the C1 and C2 cell groups. These rostrally located adrenergic neurons did not share morphological features in common with the recently described (Kalia et al., '85a) caudally located adrenergic neurons in the dorsal region of the nucleus of the tractus solitarius. These striking anatomical features of the adrenergic C1 and C2 cell groups support the proposal that adrenergic neurons in the rostral medulla oblongata play an important role in the integration of visceral functions (Fuxe et al., '80).
Adrenergic Fibers↗