Neuroactive substances in the dorsal vagal complex of the medulla oblongata: nucleus of the tractus solitarius,area postrema,and dorsal motor nucleus of the vagus

The distributions of classical and putative neurotransmitters within somata and fibres of the dorsal vagal complex are reviewed. The occurrence within the dorsal medulla oblongata of receptors specific for some of these substances is examined, and possible functional correlations of the specific neurochemicals with respect to their distribution within the dorsal vagal complex are discussed.Many of the known transmitters and putative transmitters are represented in the dorsal vagal complex, particularly within various subnuclei of the nucleus of the solitary tract, the main vagal afferent nucleus. In a few cases, some of these have been examined in detail, particularly with respect to their possible mediation of cardiovascular or gastrointestinal functions. For example, the catecholamines, substance P and angiotensin II in the nucleus of the solitary tract have all been strongly implicated as playing a role in the central control of cardiovascular function. Other neurotransmitters or putative transmitters may be involved as well, but probably to a lesser extent. Similarly, the roles in the dorsal vagal complex of dopamine, the endorphins and cholecystokinin in control of the gut have been studied in some detail.Future investigations of the distributions of and electrophysiological parameters of neurotransmitters at the cellular level should provide much needed clues to advance our knowledge of the correlations between anatomical distributions of specific neurochemicals and physiological functions mediated by them.     

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.     

Somatostatin-immunoreactive nerve cell bodies and fibers in the medulla oblongata et spinalis.

Complete serial sectioning of the medulla oblongata in monkey, cat, guinea pig, and japanese dancing mouse and incubation for somatostatin-immunoreaction was carried out. Numerous regions of the medulla oblongata such as the nucleus reticularis gigantocellularis, nucleus cuneatus et gracillis, nucleus raphe magnus, nucleus tractus solitarius, nucleus vestibularis, and parts of the oliva contain dense networks of somatostatin-immunoreactive nerve fibers. Cell bodies were seen in the nucleus reticularis medullae oblongatae. In the spinal cord the sections from each segment were analyzed, showing the highest concentrations of somatostatinergic fibers in the substantia gelantinosa of the columna dorsalis. Cell bodies were seen in the zona intermedia centralis, especially in the upper cervical segments. Many positive fibers were also seen in the entire zona intermedia and the columna ventralis. Especially prominent was the immunoreactivity in the zona intermediolateralis of the thoracic segments and the columna ventralis of the lower lumbar and sacral segments.     

Projection of cervical dorsal root fibers to the medulla oblongata in the brush-tailed possum, Trichosurus vulpecula

This study describes the projection of cervical spinal afferent nerve fibers to the medulla in the brush-tailed possum, a marsupial mammal. After single dorsal roots (between C2 and T1) were cut in a series of animals, the Fink-Heimer method was used to demonstrate the projection fields of fibers entering the CNS via specific dorsal roots. In the high cervical spinal cord, afferent fibers from each dorsal root form a discrete layer in the dorsal funiculus. The flattened laminae from upper cervical levels are lateral and those from lower cervical levels are medial within the dorsal columns. All afferent fibers at this level are separated from gray matter by the corticospinal fibers in the dorsal funiculus. All cervical roots project throughout most of the length of the well-developed main cuneate nucleus in a loosely segmentotopic fashion. Fibers from rostral roots enter more lateral parts of the nucleus, and fibers from lower levels pass to more medial areas; but terminal projection fields are typically large and overlap extensively. At more rostral medullary levels, fibers from all cervical dorsal roots also reach the external cuneate nucleus. The spatial arrangement here is more complex and more extensively overlapped than in the cuneate nucleus. Rostral cervical root fibers reach ventral and ventrolateral areas of the external cuneate nucleus and continue to its rostral pole; more caudal root fibers project to more dorsal and medial regions within the nucleus. These results demonstrate that projection patterns of spinal afferents in this marsupial are similar to those seen in the few placental species for which detailed data concerning this system are available.     

Development of catecholaminergic neurons in the human medulla oblongata

Distribution and maturation of catecholaminergic (CA) neurons have been studied by tyrosine hydroxylase immunohistochemistry in the medulla oblongata of human fetuses aged 14.5-25 weeks of gestation. Already at 14.5 weeks, CA neurons were observed in two longitudinally oriented cell clusters, one located ventrolaterally in the area of the lateral reticular and ambiguous nuclei, the other one dorsomedially forming 4 groups related to the dorsal vagal nucleus, the commissural nucleus of the vagus, the nucleus of the tractus solitarius and the area postrema. CA neurons in the area postrema were often found close to blood vessels. Scattered intermediate CA neurons were seen between these two larger clusters. CA neurons still appeared immature exhibiting bipolar morphology with only one or two short stout processes, which hardly branched. At 21 weeks, CA neurons occupied essentially the same location, but had a more mature morphology. Though still bipolar in shape, they had thinner and much longer processes which frequently branched. Both in the ventrolateral and the dorsomedial cell clusters, these processes were frequently lying close to blood vessels. At 25 weeks, CA cells had matured into multipolar neurons with long thin processes forming fine fiber networks in the ventrolateral medulla as well as around and within the dorsal vagal and solitarius nuclei. Only at this stage, a distinct CA fiber tract was seen located in the region of the tractus solitarius. Our results indicate that CA neurons in the human medulla, which are presumably involved in the control of ventilation and blood pressure, though generated rather early during development, mature relatively late.     

Immunohistochemical mapping of adrenomedullin in the human medulla oblongata

We studied by immunocytochemistry the expression of adrenomedullin (AM) in the human medulla oblongata, sampled from 13 adult subjects (mean age: 38 years), whose medical history was negative for neurological and neurovascular pathologies. Immunoreactive neurons were found in the medulla oblongata with statistically significant differences among the various nuclei (one-way ANOVA, P < 0.001). The hypoglossal nucleus showed higher AM expression than that of the spinal tract of the trigeminal nerve (P < 0.05), solitary tract nucleus (P < 0.05), nucleus intercalatus (P < 0.05), and area postrema (P < 0.05). The arcuate nucleus and inferior olivary nuclear complex showed lower AM expression than the hypoglossal nucleus (P < 0.001), vestibular nuclei (P < 0.01), cuneate and gracile nuclei (P < 0.05), lateral column of the reticular formation (P < 0.05), and nucleus ambiguous (P < 0.05). Furthermore the nuclei were grouped with reference to their function, into somatic sensitive nuclei, somatic motor nuclei, visceral nuclei, reticular formation, and nuclei involved in cerebellar functions. The ANOVA revealed statistically significant differences (P < 0.001) in mean AM scores among the different groups. Nuclei involved in cerebellar function showed the lowest mean AM score (P < 0.05). The difference in AM score between somatic motor nuclei and visceral nuclei was also statistically significant (P < 0.05). Widespread AM immunoreactivity in the nuclei of the medulla oblongata may account for the role of the peptide in neuronal function and regulation of regional blood flow. Differences in the expression of AM in the nuclei studied indicate the different involvement of AM in neurotransmission and neuromodulation.     

Glycine immunoreactive neurons in the medulla oblongata in cats

Using a highly specific antiserum to Glycine and a very sensitive immunohistochemical technique with streptavidin-HRP, we visualized for the first time a considerable number of glycine immunoreactive cell bodies and fibers in the cat medulla oblongata. These results suggest that glycine may play an essential role in nearly all the physiological functions involving the medulla oblongata, including the muscular atonia occurring during paradoxical sleep.     

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.