Apposition of enkephalin- and neurotensin-immunoreactive neurons by serotonin-immunoreactive varicosities in the rat spinal cord

Miller, Kenneth E.; Salvatierra, Alejandro

doi:10.1016/s0306-4522(97)00522-8

Cited by 21 publications

(15 citation statements)

References 71 publications

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“…Several arguments suggest that they may be inhibitory. First, 5-HT varicosities are apposed to enkephalin-and neurotensin-containing neurons in the dorsal horn (Miller and Salvatierra, 1998). Second, inhibitory interneurons might mediate serotonin-induced antinociception, through 5-HT2A receptors by potentiating the glycine-mediated Cl Ϫ currents in the superficial laminae neurons .…”

Section: Discussionmentioning

confidence: 99%

The 5‐HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons

Doly

Madeira

Fischer

et al. 2004

J of Comparative Neurology

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Serotonin (5-HT) plays a major role at the spinal level by modulating most spinal functions through several receptor subtypes including the 5-HT2A receptor. To gain further insight into the cellular role of this receptor, we performed an immunocytochemical study of 5-HT2A receptors in the rat spinal cord, at light and electron microscope levels. The results showed that 5-HT2A receptors were widely distributed in the spinal cord at all segmental levels. Immunolabeling was particularly dense in lamina IX and in the dorsal horn lamina IIi. Immunoreactive cell bodies were numerous in lamina IX, where many but not all motoneurons were labeled, as shown by double labeling with choline acetyltransferase antibodies. Stained cell bodies were also observed in the gray matter. The study at the ultrastructural level focused on the lumbar dorsal horn (laminae I-II) and ventral horn (lamina IX). At both levels, 5-HT2A immunoreactivity was mainly postsynaptic on dendrites and cell bodies. However, a little presynaptic labeling was also observed in axon and axon terminals, some of them containing large granular vesicles attesting to their peptidergic nature. The main result of our study was the "nonsynaptic" plasma membrane localization of 5-HT2A receptors covering a large surface of cell bodies and dendrites, suggesting a paracrine form of action of serotonin. These observations are consistent with a double role (pre- and postsynaptic) for serotonin on these receptors on various cellular targets.

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Section: Discussionmentioning

confidence: 99%

The 5‐HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons

Doly

Madeira

Fischer

et al. 2004

J of Comparative Neurology

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“…We measured the tissue volume processed for DBH-immunoreactivity using Openlab (Improvision Inc., Lexington, MA) software and calculated the DBH-fiber density. NA varicosities adjacent to cholinergic neurons were quantified as reported in Takeoka et al (2009) and similar to that used by (Miller and Salvatierra, 1998; Mullner et al, 2008). The quantification method is based on the assumption that NA is released both synaptically and non-synaptically and does not distinguish between these transmission modes.…”

Section: Methodsmentioning

confidence: 99%

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Takeoka

Kubasak

Zhong³

et al. 2010

Experimental Neurology

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Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons.

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“…Our results do not distinguish between serotonergic synaptic contacts and nonsynaptic associations that utilize volume transmission (Ridet et al, 1993; Bunin and Wightman, 1999; Zoli et al, 1999). Serotonergic varicosities adjacent to cholinergic neurons were quantified with a technique similar to that used by Miller and Salvatierra (1998) and Mullner et al (2008), whose studies are also based on the assumption that 5-HT utilizes nonsynaptic transmission. Since Kubasak et al (2008) did not find a training effect on the number of plantar steps during treadmill locomotion for either OEG- or media-injected rats, our analyses primarily focused on differences between the OEG and media transplantations.…”

Section: Methodsmentioning

confidence: 99%

Serotonergic innervation of the caudal spinal stump in rats after complete spinal transection: Effect of olfactory ensheathing glia

Takeoka

Kubasak

Zhong

et al. 2009

J of Comparative Neurology

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Spinal cord injury studies use the presence of serotonin (5-HT)-immunoreactive axons caudal to the injury site as evidence of axonal regeneration. As olfactory ensheathing glia (OEG) transplantation improves hindlimb locomotion in adult rats with complete spinal cord transection, we hypothesized that more 5-HT-positive axons would be found in the caudal stump of OEG-than media-injected rats. Previously we found 5-HT-immunolabeled axons that spanned the transection site only in OEGinjected rats but detected labeled axons just caudal to the lesion in both media-and OEG-injected rats. Now we report that many 5-HT-labeled axons are present throughout the caudal stump of both media-and OEG-injected rats. We found occasional 5-HT-positive interneurons that are one likely source of 5-HT-labeled axons. These results imply that the presence of 5-HT-labeled fibers in the caudal stump is not a reliable indicator of regeneration. We then asked if 5-HT-positive axons appose cholinergic neurons associated with motor functions: central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments of OEGthan media-injected rats. SMNs and partition cells are less frequently apposed. As nonsynaptic release of 5-HT is common in the spinal cord, an increase in 5-HT-positive varicosities along motorassociated cholinergic neurons may contribute to the locomotor improvement observed in OEGinjected spinal rats. Furthermore, serotonin located within the caudal stump may activate lumbosacral locomotor networks. J. Comp. Neurol. 515: 664-676, 2009. Indexing termsplasticity; locomotion; OEG; spinal cord injury; 5-HT; ChAT; cholinergic neurons Adult cats and neonatal rats with completely transected spinal cords (i.e., spinal animals) can be trained to generate fairly coordinated patterns of hindlimb stepping on the treadmill in the absence of supraspinal connections (Lovely et al., 1986;Barbeau et al., 1987;de Leon et al., 1998;Joynes et al., 1999;Jordan and Schmidt, 2002;Edgerton et al., 2004;Kubasak et al., 2005). In contrast, adult spinal rats do not demonstrate coordinated locomotor stepping without therapeutic interventions. Electrical and/or pharmacological interventions, including serotonin (5-HT) receptor agonists that likely activate central pattern generation in the lumbosacral cord, can facilitate bipedal stepping in adult spinal rats (Ichiyama et al., 2005;Lavrov et al., 2006;Gerasimenko et al., 2007). In addition to evidence from in vivo studies, in vitro neonatal models showed that 5-HT is involved in the alternating firing of the contralateral neural networks to *Correspondence to: Patricia E. Phelps, PhD, Dept. of Physiological Science, UCLA, Box 951606, Los Angeles, CA 90095-1606. pphelps@physci.ucla.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript elicit bilateral locomotor-like activity (Cazalets et al., ...

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Apposition of enkephalin- and neurotensin-immunoreactive neurons by serotonin-immunoreactive varicosities in the rat spinal cord

Cited by 21 publications

References 71 publications

The 5‐HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons

The 5‐HT2A receptor is widely distributed in the rat spinal cord and mainly localized at the plasma membrane of postsynaptic neurons

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: Effects of olfactory ensheathing glia

Serotonergic innervation of the caudal spinal stump in rats after complete spinal transection: Effect of olfactory ensheathing glia

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