Simultaneous ultrastructural localization of tritiated serotonin and immunoreactive peptides.

Basbaum, Allan I.; Glazer, Ellyn J.; Lord, Barbara A.

doi:10.1177/30.8.7119422

Cited by 19 publications

(3 citation statements)

References 4 publications

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“…This is particularly true for the RMc neurons, which we previously demonstrated target the dorsal horn (Basbaum et al, 1978). Our results suggest, therefore, that RVM serotonergic neurons influence spinal cord nociceptive processing both directly, via a 5HT projection to the dorsal horn (Basbaum et al, 1982;VanderHorst and Ulfhake, 2006) and indirectly, via a polysynaptic pathway involving the spinally projecting, non-5HT cell populations. To what extent the latter control circuit arises from "on" and "off" cells cannot be determined from our analysis; however, Potrebic et al (1995) reported that 5HT neurons and "off" cells receive the highest density of 5HT appositions.…”

Section: Local Connections Made By Serotonergic Neurons In the Medullmentioning

confidence: 66%

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

Bráz

Basbaum

2008

J of Comparative Neurology

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Despite the evidence for a significant contribution of brainstem serotonergic (5HT) systems to the control of spinal cord "pain" transmission neurons, attention has turned recently to the influence of nonserotonergic neurons, including the facilitatory and inhibitory controls that originate from socalled "on" and "off" cells of the rostroventral medulla (RVM). Unclear, however, is the extent to which these latter circuits interact with or are influenced by the serotonergic cell groups. To address this question we selectively targeted expression of a transneuronal tracer, wheat germ agglutinin (WGA), in the 5HT neurons so as to study the interplay between the 5HT and non-5HT systems. In addition to confirming the direct medullary 5HT projection to the spinal cord we also observed large numbers of non-5HT neurons, in the medullary nucleus reticularis gigantocellularis and magnocellularis, that were WGA-immunoreactive, i.e., were transneuronally labeled from 5HT neurons. Fluoro-Gold injections into the spinal cord established that these reticular neurons are not only postsynaptic to the 5HT neurons of the medulla, but that most are also at the origin of descending, bulbospinal pathways. By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons. Finally, we found very few examples of WGA-immunoreactive noradrenergic neurons, which suggests that there is considerable independence of the monoaminergic bulbospinal pathways. Our results indicate that 5HT neurons influence "pain" processing at the spinal cord level both directly and indirectly via feedforward connections with multiple non-5HT descending control pathways. Indexing termsWGA; pain; serotonin; brainstem; analgesia; RVM Until recently, studies of the bulbospinal systems that originate from the rostral ventral medulla (RVM) emphasized their contribution to inhibitory control of "pain" transmission. HHS Public AccessAuthor manuscript J Comp Neurol. Author manuscript; available in PMC 2016 July 16. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptMost important, opioid injection into or electrical stimulation of the midbrain periaqueductal gray (PAG) activates these descending pathways and concurrently produces a profound antinociceptive action, including inhibition of the firing of dorsal horn nociresponsive neurons and behavioral analgesia (Basbaum and Fields, 1984). Although neurochemically distinct pathways arise from the RVM, considerable evidence pointed to the contribution of medullary serotonergic neurons. For example, morphine evokes the release of serotonin at the level of the spinal cord and RVM (Matos et al., 1992;Taylor and Basbaum, 2003) and serotonin depletion using pharmacological or ablative procedures blocks the analgesia induced by systemic administration of morphine (Vogt, 1974;Proudfit and Anderson, 1975;Yaksh et al., 1977).In agreement with these findings, Zhao et al. (2007a,b) reported that inflammatory pai...

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Section: Local Connections Made By Serotonergic Neurons In the Medullmentioning

confidence: 66%

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

Bráz

Basbaum

2008

J of Comparative Neurology

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“…These are reminiscent of the marginal and stalked cells found in the spinal cord to receive an abundant 5-HT axodendritic innervation (Miletic et al, 1984). Double-labeling studies using tritiated 5-HT autoradiography combined with ENK immunocytochemistry confirmed a 5-HT to ENK linkage onto precisely these kinds of cells in laminae I and I1 (Basbaum et al, 1982).…”

Section: Discussionmentioning

confidence: 77%

Immunocytochemistry of enkephalin and serotonin distribution in restricted zones of the rostral trigeminal spinal subnuclei: Comparisons with subnucleus caudalis

Matthews

Hernandez

Liles

1987

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The spinal trigeminal subnucleus caudalis processes nociceptive input from the head. However, physiological and behavioral studies in monkeys and humans indicate that painful stimuli from the central face and oral cavity also project through trigeminal nuclei rostral to the spinal subnucleus caudalis. Both enkephalin (ENK) and serotonin (5-HT) are present in rostral trigeminal nuclei and these regions receive inputs from the raphe complex. Thus, it appears that elements of pain-modulating circuitry proposed by Basbaum and Fields (Annu. Rev. Neurosci., 7:309-338, 1984) for the spinal and medullary dorsal horn may also exist in this region. In order to begin an exploration of this circuitry, the present study combines the techniques of retrograde transport of HRP from the ventral posteromedial thalamic nucleus (VPM) of the cat's thalamus to label trigeminothalamic relay cells. Secondarily, immunocytochemical techniques are employed to define the distribution patterns of ENK and 5-HT cells and terminals in relationship to both labeled and nonlabeled neurons in each of the subnuclei of the spinal trigeminal nucleus. Trigeminothalamic relay cells were observed in laminae I and II, the magnocellular region, and the interstitial nucleus (IN) of subnucleus caudalis (Vc). ENK was found in axodendritic and axosomatic terminals, together with a population of small fusiform neurons in all these same areas except the magnocellular region. ENK axosomatic contacts innervated approximately 30% of labeled relay cells, chiefly in lamina I and the IN, or small unlabeled neurons in the same area. Serotonin activity occurred principally in lamina I and the IN and was confined almost exclusively to axodendritic terminals. Examination of subnucleus interpolaris (Vi) revealed relay cells distributed throughout the length of the nucleus and increasing in numbers at rostral levels. A rostral extension of the IN was found just ventrolateral to the main body of Vi and contained numerous labeled cells. The distribution of ENK activity was restricted to the ventral part of Vi and the IN and occurred in axodendritic and axosomatic terminals. These latter elements innervated 30-40% of labeled relay cells in Vi, particularly those located in the IN. Cells containing ENK generally resembled the fusiform cells found in Vc and were distributed in ventral Vi and the IN. Some ENK cells were larger, displayed several dendrites, and occurred only in the ventral Vi. Serotonin within Vi and Vc was confined principally to axodendritic terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The nucleus raphe magnus and related reticular nuclei have been shown to have serotoninergic, enkephalinergic, and other peptidergic projections to those brainstem and spinal cord nuclei that relay nociceptive inputs from the periphery (Basbaum and Fields, 1984;Basbaum et al, 1978Basbaum et al, , 1982Dostrovsky et al, 1982Dostrovsky et al, , 1983Dubner and Bennett, 1983;Dubner et al, 1984;Menetrey and Basbaum, 1987;Millan, 1986;Willis, 1982Willis, , 1984Willis, , 1985a. The medullary (Vc) and spinal dorsal horns have received the most attention.…”

Section: Introductionmentioning

confidence: 99%

Synaptic substrates for enkephalinergic and serotoninergic interactions with dental primary afferent terminals in trigeminal subnucleus interpolaris: An immunocytochemical study using peroxidase and colloidal gold

Matthews

Hernandez

Hoffmann

et al. 1989

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Pain processing in the trigeminal complex has been thought to reside primarily in the spinal subnucleus caudalis (Vc). However, trigeminal tractotomies eliminating primary afferent input to Vc and severance of secondary trigemino-thalamic fibers from Vc do not disturb pain perception from the central face and oral cavity. Furthermore, large numbers of neurons that are highly responsive to noxious stimuli and suppressed by inputs from the periaqueductal gray and raphe complex have been identified in subnuclei interpolaris (Vi) and oralis (Vo). Therefore, the purpose of this study was to assess the distribution and spatial arrangements of nociceptive modulatory transmitters with nociceptive afferents and trigemino-thalamic relay cells in the rostral portion of the spinal trigeminal nuclear complex. The dental pulp contains predominantly nociceptors that project to all three subdivisions of the trigeminal spinal complex. These projections were visualized by anterograde transganglionic transport of horseradish peroxidase or by degeneration following administration of toxic ricin to the pulp chambers. The spatial arrangements of dental primary afferents with enkephalinergic (ENK) and serotoninergic (5HT) inputs was then assessed by employing avidin-biotin peroxidase and protein-A colloidal gold double-labeling immunocytochemistry. Trigemino-thalamic relay cells were also labeled by retrograde transport of HRP after stereotaxic injections into the ventrobasal thalamus. ENK and 5HT immunoreactivity was found in the ventrolateral quadrant and lateral margin of Vi, together with the adjacent interstitial nucleus (IN). This activity extended from the caudal pole of Vi and the periobex region, where it was most dense, rostrally to a position approximately 2.9 mm from the Obex. Neither ENK nor 5HT immunoreactivity was observed in Vo. Primary dental afferents projected into the ventromedial quadrant of rostral Vi and were found in the ventrolateral quadrant and dorsal aspect of the subnucleus farther caudally. They appeared as simple boutons with single contacts or as larger, sometimes scalloped terminals that formed multiple contacts. Postsynaptic elements were usually small dendritic profiles, although relay cell somata rarely received primary afferent inputs. Many primary afferents entered areas of synaptic clustering and contacted enkephalinergic dendrites, some of which were also postsynaptic to serotoninergic synapses. Alternatively, primary afferents contacted unlabeled processes that were also postsynaptic to the enkephalinergic element to form a triad arrangement. The least common occurrence was axo-axonic contacts in which enkephalinergic synapses were presynaptic to primary afferents. Both enkephalinergic and serotoninergic synaptic categories displayed round vesicles and generally formed asymmetric junctions.(ABSTRACT TRUNCATED AT 400 WORDS)

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Simultaneous ultrastructural localization of tritiated serotonin and immunoreactive peptides.

Cited by 19 publications

References 4 publications

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

Immunocytochemistry of enkephalin and serotonin distribution in restricted zones of the rostral trigeminal spinal subnuclei: Comparisons with subnucleus caudalis

Synaptic substrates for enkephalinergic and serotoninergic interactions with dental primary afferent terminals in trigeminal subnucleus interpolaris: An immunocytochemical study using peroxidase and colloidal gold

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