Distribution of phenylethanolamine N-methyltransferase cell bodies, axons, and terminals in monkey brainstem: an immunohistochemical mapping study.

Adrenaline (epinephrine) is an important candidate transmitter in descending spinal control systems. To date intrinsic spinal adrenergic neurons have not been reported; thus adrenergic input is presumably derived from brainstem sites. In this regard, the localization of adrenergic neurons in the brainstem is an important consideration. Maps of adrenergic cell bodies and to a lesser extent axons and terminal fields have been made in various species, but not in monkeys. Thus, the present study concerns the organization of adrenergic systems in the brainstem of a monkey (Macaca fascicularis) immunohistochemically mapped by means of an antibody to the enzyme phenylethanolamine N-methyltransferase (PNMT). PNMT-immunostained cell bodies are distributed throughout the medulla in two principal locations. One concentration of labeled cells is in the dorsomedial medulla and includes the nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (X), and an area ventral to X in a region of the reticular formation (RF) known as the central nucleus dorsalis (CnD) of the medulla. A few scattered cells are observed in the periventricular gray just ventral to the IVth ventricle and on midline in the raphe. The second major concentration of PNMT-immunostained cells is located in the ventrolateral RF, lateral and dorsolateral to the inferior olive (IO), including some cells in the rostral part of the lateral reticular nucleus (LRN). Terminal fields are located in the NTS, X, area postrema (AP), and the floor of the IVth ventricle in the medulla and pons. A light terminal field is also observed in the raphe, particularly raphe pallidus (RP). A heavy terminal field is present in locus coeruleus (LC). Fibers labeled for PNMT form two major fiber tracts. One is in the dorsomedial RF extending as a well-organized bundle through the medulla, pons, and midbrain. A second tract is located on the ventrolateral edge of the medulla and caudal pons. Fibers in this tract appear to descend to the spinal cord. A comparison with maps of other catecholamine neurons in primates is discussed, confirming that the distribution of the adrenergic system in monkeys is similar to that described in the human.

Immunocytochemical identification of long ascending peptidergic neurons contributing to the spinoreticular tract in the rat.

In the present study, we examined the peptidergic content of lumbar spinoreticular tract neurons in the colchicine-treated rat. This was accomplished by combining the retrograde transport of the fluorescent dye True Blue with the immunocytochemical labeling of neurons containing cholecystokinin-8, dynorphin A1-8, somatostatin, substance P or vasoactive intestinal polypeptide. After True Blue injections into the caudal bulbar reticular formation, separate populations of retrogradely labeled cells were identified as containing cholecystokinin-like, dynorphin-like, substance P-like or vasoactive intestinal polypeptide-like immunoreactivity. Retrogradely labeled somatostatin-like neurons were not identified in any of the animals examined. Each population of double-labeled cells showed a different distribution in the lumbar spinal cord. The highest yield of double-labeling occurred for cholecystokinin, with 16% of all intrinsic cholecystokinin-like neurons containing True Blue. These double labeled neurons were found predominantly at the border between lamina VII and the central canal region. About 11% of intrinsic vasoactive intestinal polypeptide-like neurons in the lumbar spinal cord were retrogradely labeled from the bulbar reticular formation. These neurons were found mostly in the lateral spinal nucleus, with only a few double-labeled cells located deep in the gray matter. Dynorphin-like double-labeled neurons were localized predominantly near the central canal; a smaller population was also seen in the lateral spinal nucleus. It was found that double-labeled dynorphin-like neurons made up 8% of all intrinsic dynorphin-like neurons. Retrogradely-labeled substance P-like neurons were rare; the few double-labeled neurons were found in the lateral spinal nucleus and lateral lamina V. These findings suggest a significant role for spinal cord peptides in long ascending systems beyond their involvement in local circuit physiology.

The frontal eye field and prefrontal cortex project to the paramedian pontine reticular formation in the cat.

Transcannular microinjections of horseradish peroxidase were made into the paramedian pontine reticular formation (PPRF) in adult cats to identify regions of the cerebral cortex having direct influence on this important center for the production of saccadic eye movements. The majority of retrogradely labeled cortico-(ponto)reticular neurons were located in lamina V of the dorsomedial precruciate shoulder cortex and presylvian sulcal cortex, the medial and lateral frontal eye fields of the cat respectively. In most cases, labeled cells also extended into the gyrus proreus, the cat prefrontal cortex.

Comparison of neuropeptide Y immunoreactivity in hypothalamic and brainstem nuclei of young and mature spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The concentration of neuropeptide Y immunoreactivity (NPY-ir) was measured in 8 hypothalamic and 5 brainstem nuclei of 6- and 14-week-old spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Strain differences were observed in 3 hypothalamic nuclei and age-dependent changes occurred in 3 hypothalamic and 2 brainstem nuclei. In both the ventromedial hypothalamic nucleus and locus coeruleus the observed change in NPY-ir with age in SH rats was significantly different to the change observed in the WKY. These strain- and age-related differences in NPY-ir may be of relevance in the development of hypertension in the SH rat.

A long ascending pathway of enkephalin-like immunoreactive spinoreticular neurons in the rat.

In the present study, we examined whether some long ascending spinal cord neurons contain enkephalin by combining the retrograde transport of the fluorescent dye True Blue with enkephalin immunocytochemistry. Evidence is presented for the existence of enkephalin in a subpopulation of spinoreticular neurons in the rat located in the central canal region and adjacent gray matter.

Cerebellar vermis: essential for long-term habituation of the acoustic startle response.

The acoustic startle response in rats shows both short-term habituation, which recovers in seconds or minutes, and long-term habituation, which is effectively permanent. Lesions of the cerebellar vermis significantly attenuated long-term habituation without affecting the short-term process or altering initial response levels. In this response system the cerebellar vermis is part of an essential circuit for long-term habituation.

Muscarinic cholinergic receptors and the canine model of narcolepsy.

The role of the muscarinic cholinergic receptor in narcolepsy was examined using radioligand binding to various brain regions of normal and genetically narcoleptic Doberman pinschers. In this multi-litter study, a previous report of a proliferation of muscarinic cholinergic receptors in the brainstem was confirmed, and the concentration of the M2 receptor subtype, in particular, was elevated. This up-regulation of brainstem cholinergic receptors suggests a problem with release of acetylcholine, which, together with previous reports of an impairment of dopamine release, may be indicative of a fundamental membrane problem in narcolepsy.

The ultrastructural identification of reticulo-hypoglossal axon terminals anterogradely labeled with horseradish peroxidase.

Injections of horseradish peroxidase (HRP) or wheat-germ agglutinin-horseradish peroxidase (WGA-HRP) into the nucleus reticularis parvocellularis (RPc) produced anterograde labeling of axon terminals within the hypoglossal nucleus. Based on morphological parameters of vesicle population, membrane specializations, and postsynaptic articulations, two types of axon terminals derived from neurons in RPc end on hypoglossal neurons. More than half of the terminals contained spherical vesicles (S-type), established asymmetrical membrane specializations and contacted proximal and medium-sized dendrites. The remaining labeled terminals had flattened vesicles (F-type), symmetrical membrane densities and apposed medium and small dendrites. The morphological differences expressed in the two types of terminals may reflect physiological and/or pharmacological differences in the action of RPc neurons on motoneurons in the hypoglossal nucleus.

Octanoic acid-induced coma and reticular formation energy metabolism.

The medium chain fatty acid octanoic acid was injected i.p. into 20-22 g Swiss-Albino mice at a dose of 15 mumol/g. This dose produced a reproducible response consisting of a 3-4 min period of drowsiness, followed by coma. These mice as well as suitable controls were sacrificed by rapid submersion in liquid N2, or by microwave irradiation in a 7.3 kW microwave oven. Tissue from the reticular formation and the inferior colliculus was prepared for microanalysis of the energy metabolites glucose, glycogen, ATP and phosphocreatine. Results from this study showed a selective effect on energy metabolism in cells of the reticular formation. Both glucose and glycogen were elevated in the coma and precoma state. In addition, ATP and phosphocreatine were decreased in the reticular formation during coma. These results show a selective effect of octanoic acid on energy metabolism in the reticular formation both in the precoma stage, and during overt coma. The selective vulnerability of the reticular formation to metabolic insult may act in a beneficial manner to the animal by inducing coma. This lowers the overall demand for energy, thereby placing the animal in a milieu in which there is an increased chance for correction of the perturbation.

An electrochemical approach to sleep metabolism: a pO2 paradoxical sleep system.

Oxygen cathodes chronically implanted in the cat brain recorded changes of local oxygen concentration during paradoxical sleep. Phasic high amplitude pO2 changes were consistently observed in some regions and were characterized by a dramatic increase in the amplitude of the oscillations. The regions displaying these responses included part of the reticular formation, hypothalamus, amygdala and cerebellum which we refer to as the "pO2 paradoxical sleep system." This pO2 pattern was not observed in white matter, in the neocortex or in specific thalamic nuclei. It is postulated that the phasic response is due to a local increase of neuronal activity requiring increased oxygen availability and augmented protein synthesis during paradoxical sleep and may form part of a system related to "plastic" phenomena.

[Changes in the oxygen tension and bioelectrical activity of the brains of animals subjected to acute hypoxia]. / Izmeneniia napriazheniia kisloroda i bioélektricheskoi aktivnosti golovnogo mozga zhivotnykh pri vozdeistvii ostroi giposksii

Simultaneous recording of oxygen tension (pO2) and bioelectrical activity led from different cerebral structures was made in rabbits and rats with implanted electrodes under conditions of acute hypoxia. Marked activation of the EEG as electrophysiological correlate of behavioural response was observed in rabbits only at the beginning of "ascent" and "descent". The EEG, respiration, and cardiac activity changes associated with the drop of PO2 in the brain tissue (activation of these parameters at the low "altitude" /2000-6000 m/ and their suppression at the maximal "altitudes" /8500 m/) were of approximately of the same character in both species.

Some aspects of the organization of the thalamic reticular complex.

Anatomical methods which depend upon the anterograde axonal transport of isotopically labeled neuronal proteins or the retrograde axonal transport of the enzyme, horseradish peroxidase, have been used to elucidate the relationships between the reticular complex and the dorsal thalamus and cerebral cortex. Injections of tritiated amino acids in the dorsal thalamus or cerebral cortex in rats, cats and monkeys, show that as the bundles of thalamo-cortical and cortico-thalamic fibers joining a particular dorsal thalamic nucleus to its associated area of the cerebral cortex traverse the reticular complex, they each give rise to a dense zone of terminals occupying a sector of the reticular complex which is relatively constant for that dorsal thalamic nucleus and cortical area. However, because of the wide extent of the dendritic fields of the reticular cells and the degree of overlap between the sectors of the complex subtended by adjacent dorsal thalamic nuclei and adjacent cortical areas, it is likely that the reticular complex samples thalamo-cortical and cortico-thalamic activity in a somewhat unspecific manner. Fibers passing to the reticular complex from the intralaminar nuclei of the thalamus appear to be associated with the projection from the intralaminar nuclei to the striatum. Injections of tritiated amino acids in the reticular complex itself and injections of horseradish peroxidase in various other parts of the brain show that the only efferent pathway from the reticular complex terminates in the nuclei of the dorsal thalamus. The reticular complex does not appear to send fibers to other components of the ventral thalamus nor to the cerebral cortex.

Monoamine distribution in primate brain. I Catecholamine-containing perikarya in the brain stem of Macaca speciosa.

The distribution of catecholamine-containing cell bodies was examined in the brain stem of Macaca speciosa using the Falck-Hillarp histofluorescence technique. Extensive accumulations of such cells were seen in the ventral tegmental area, locus coeruleus, mesencephalic reticular formation and ventrolateral reticular formation of pons and medulla. This distribution was compared to that previously reported in rat, cat, squirrel monkey and human brain. Apparent species dissimilarities and similarities are reported.