Robert M. Bowker

Quantitative re-evaluation of descending serotonergic and non-serotonergic projections from the medulla of the rodent: evidence for extensive co-existence of serotonin and peptides in the same spinally projecting neurons, but not from the nucleus raphe magnus.

A quantitative analysis of serotonin (5-HT) and spinally-projecting neurons was re-evaluated in the rodent. The findings indicate that most (nearly 90%) of the medullary 5-HT neurons projected to the lumbar spinal cord, and most (up to 85%) of the spinally projecting neurons within the distribution of the serotonergic neurons contained 5-HT immunoreactivity. However, in nucleus raphe magnus (NRM) only about two-thirds of the projection cells were 5-HT immunoreactive. These data support two general conclusions: (1) the raphe-spinal system consists primarily of an extensive 5-HT pathway with neuronal subsets containing the co-localized peptides. Only the NRM contains a major non-5-HT projection. (2) As most of the medullary 5-HT neurons project to the caudal spinal segments of the rodent, collateralization of individual 5-HT neurons is extensive and widespread, existing to different spinal cord levels, as well as to other medullary nuclei, e.g., cranial nerve and inferior olivary nuclei. These findings argue that although differences are present within the 5-HT distributions, the raphe-spinal system as a whole should be considered to be a relatively homogeneous pathway containing 5-HT as the common element rather than as separate populations containing major projections of 5-HT alone, 5-HT co-localized with peptides and peptides without 5-HT.

Peptidergic neurons in the nucleus raphe magnus and the nucleus gigantocellularis: Their distributions, interrelationships, and projections to the spinal cord

Publisher Summary This chapter discusses the identification, distribution, and connectivity of several species of peptidergic neurons within the nucleus raphe magnus (NRM) and the nucleus gigantocellularis (NGC). The anatomical organization of the neurotransmitters in these two nuclei is described. The neurotransmitters are not homogeneously distributed throughout these two cell groups and are segregated into subpopulations. While the neurotransmitter identities of several of these inputs are known, including the catecholamines, enkephalin (ENK) and neurotensin, many inputs to these cell groups are not yet identified. Future work designed to unravel the anatomical complexities of these nuclei to understand the circuitry involved in the descending control of nociception must focus on a small number of the neurotransmitter elements within the NRM/ NGC region and must analyze all potential transmitter interactions in terms of their coded afferents and efferent projections, the intrinsic neurons and the receptor organization. Only then can these two critical links in the rostral medulla in the descending control of nociception is understood.

Serotonergic and peptidergic inputs to the primate ventral spinal cord as visualized with multiple chromagens on the same tissue section

Primate spinal cord tissue sections were sequentially incubated in serotonin (5-HT), substance P (SP) and methionine-enkephalin antisera and reacted immunocytochemically. The findings indicate that virtually all SP-like immunoreactivity coexists with 5-HT in the ventral horn, while an additional group of 5-HT terminals do not contain SP immunoreactivity.

Variability in the characteristics of pontogeniculooccipital spikes during paradoxical sleep

An important criterion for identifying paradoxical sleep is the presence of a peculiar waveform recorded in the pons, lateral geniculate body, and visual cortex during that sleep state. These waveforms, termed PGO waves, have long been viewed as having large and constant amplitudes, an initial negative deflection in the visual cortex, and not being dependent on the levels of background illumination. Waveforms recorded during wakefulness have different characteristics, and these have been used to differentiate the waking state from paradoxical sleep. The present study demonstrated that most PGO waves have highly variable amplitudes during paradoxical sleep and that only a small fraction conform to the stereotypic wave characteristics of constant and large amplitudes and the presence of initial negative deflections. These findings argue against the criteria commonly used to differentiate PGO waves during paradoxical sleep from the eye movement potentials recorded in wakefulness.

Serotonergic and non-serotonergic raphe neurons projecting to the feline lumbar and cervical spinal cord: A quantitative horseradish peroxidase-immunocytochemical study

A quantitative study of raphe-spinal neurons and serotonergic neurons in 3 medullary raphe nuclei in the cat indicates that more than 80% of the raphe-spinal neurons that project to the spinal cord are serotonergic raphe-spinal neurons in each of the nuclei. More than 85% of the descending raphe-spinal neurons in the two caudal nuclei, nucleus raphe pallidus and nucleus raphe obscurus, are serotonergic, whereas 75% of the raphe-spinal neurons in the more rostrally placed nucleus raphe magnus contain serotonin (5-HT). These results are discussed in relation to descending systems containing both neuropeptides and 5-HT and collateralizing to several spinal segments.

Distribution of μ-opioid receptors in the nucleus raphe magnus and nucleus gigantocellularis: A quantitative autoradiographic study

The present study has described and quantitated the distribution of mu-opioid receptors in the nucleus raphe magnus (NRM) and nucleus gigantocellularis (NGC), using in vitro autoradiography. Moderately dense binding of a mu-enkephalin analog, DAGO, was observed in the NRM and adjacent parts of the NGC. DAGO binding density was greatest in the anterior NRM, possibly due to a greater involvement in the descending, opiate-mediated modulation of nociception. These findings agree with proposed roles for this region in the central regulation of pain.

Descending modulation of dorsal horn biogenic amines as determined by in vivo dialysis

Bipolar concentric stimulating electrodes were placed medially within the nucleus raphe magnus and laterally within the nucleus gigantocellularis. The levels of norepinephrine (NE), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) within the dorsal horn of the spinal cord were measured before and after electrical stimulation of these brainstem nuclei using in vivo dialysis coupled with high pressure liquid chromatography and electrochemical detection. Stimulation medially significantly increased the levels of all three amines. While simulation laterally also increased NE, both 5-HT and 5-HIAA were significantly reduced. The relevance of these findings to descending modulation of ascending nociceptive neural activity within the dorsal horn is discussed.

Differential labeling of the vestibular complex following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus

Following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus (LC), bilateral retrograde labeling was evident in all 4 vestibular nuclei. In both species, the major contributions of LC afferents arose from the ipsilateral rather than the contralateral vestibular nuclei. Quantitative analysis in the rat has indicated that approximately 90% of the total vestibular-LC projections originated from the ipsilateral vestibular nuclear complex, with 10% from the contralateral. The frequency distribution was in the order of lateral greater than medial greater than superior greater than inferior vestibular nuclei.

Evoked changes in 5-hydroxytryptamine and norepinephrine release: in vivo dialysis of the rat dorsal horn.

Basal 5-hydroxytryptamine (5HT) and norepinephrine (NE) concentrations were measured in samples collected by in vivo dialysis of the rat dorsal horn. Infusion of KCl, glutamate, and NE by means of the dialysis probe increased NE, but decreased 5HT extracellular concentrations. In contrast, electrical stimulation of the nucleus raphe magnus increased the recovery of both NE and 5HT. These findings suggest differential regulation of noradrenergic and serotonergic nerve terminals modulating nociceptive neurotransmission within the dorsal horn.

The relationship between descending serotonin projections and ascending projections in the nucleus raphe magnus: a double labeling study

The nucleus raphe magnus and rostral parts of the nucleus raphe obscurus were found to have extensive efferent projections: a major ascending non-serotonergic (5-HT) projection through the median forebrain bundle, and a descending system consisting of both 5-HT and non-5-HT neurons. Differences in the localizations of their cells of origin suggest that they form two distinct efferent systems from the caudal medullary raphe nuclei.