Effects of NMDA and its antagonists on ventral horn cholinergic neurons in organotypic roller tube spinal cord cultures

1997 ◽  
Vol 104 (1) ◽  
pp. 31-51 ◽  
Author(s):  
J. R. Delfs ◽  
D. M. Saroff ◽  
Y. Nishida ◽  
J. Friend ◽  
C. Geula

2008 ◽  
Vol 53 (No. 8) ◽  
pp. 434-444 ◽  
Author(s):  
J. Calka ◽  
M. Zalecki ◽  
K. Wasowicz ◽  
M.B. Arciszewski ◽  
M. Lakomy

Present knowledge concerning the organization of cholinergic structures of the spinal cord has been derived primarily from studies on small laboratory animals, while there is a complete lack of information concerning its structure in the pig. In the present study we employed choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry to identify the cholinergic neuronal population in the thoracolumbar and sacral spinal cord of the pig. The distribution of ChAT-, VAChT- and AChE-positive cells was found to be similar. Distinct groups of cholinergic neurons were observed in the gray matter of the ventral horn, intermediolateral nucleus, intermediomedial nucleus as well as individual stained cells were found in the area around the central canal and in the base of the dorsal horn. Double staining confirmed complete colocalization of ChAT with AChE in the ventral horn and intermediolateral nucleus although in the intermediomedial nucleus only 64% of the AChE-positive neurons expressed ChAT-immunoreactivity, indicating unique, region restricted, diversity of ChAT and AChE staining. Our results revealed details concerning spatial distribution and morphological features of the cholinergic neurons in the thoracolumbar and sacral spinal cord of the pig. We also found that the pattern of distribution of cholinergic neurons in the porcine spinal cord shows great similarity to the organization of the cholinergic system in other mammalian species studied.



1996 ◽  
Vol 84 (6) ◽  
pp. 992-998 ◽  
Author(s):  
Thomas H. Milhorat ◽  
Harrison T. M. Mu ◽  
Carole C. LaMotte ◽  
Ade T. Milhorat

✓ The distribution of substance P, a putative neurotransmitter and pain-related peptide, was studied using the peroxidase—antiperoxidase immunohistochemical method in the spinal cords obtained from autopsy of 10 patients with syringomyelia and 10 age- and sex-matched, neurologically normal individuals. Substance P immunoreactivity was present in axons and in terminal-like processes in close apposition to neurons in the first, second, and third laminae of the dorsal horn. Smaller amounts of peroxidase-positive staining were found in the fifth lamina of the dorsal horn, the intermediolateral nucleus, the intermediomedial nucleus, and the ventral horn. In nine of 10 patients with syringomyelia, there was a substantial increase in substance P immunoreactivity in the first, second, third, and fifth laminae below the level of the lesion. A marked reduction or absence of staining was present in segments of the spinal cord occupied by the syrinx. Central cavities produced bilateral abnormalities, whereas eccentric cavities produced changes that were ipsilateral to the lesion. No alterations in staining were found in the spinal cord of an asymptomatic patient with a small central syrinx. The authors conclude that syringomyelia can be associated with abnormalities in spinal cord levels of substance P, which may affect the modulation and perception of pain.



2018 ◽  
Vol 120 (3) ◽  
pp. 998-1009 ◽  
Author(s):  
David Acton ◽  
Matthew J. Broadhead ◽  
Gareth B. Miles

Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behavior. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysis of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signaling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways. Here, we demonstrate that adenosine produced upon astrocytic stimulation modulates locomotor-related activity by counteracting the excitatory effects of D1LR signaling and does not act by previously described dopamine-independent pathways. In spinal cord preparations from postnatal mice, a D1LR agonist, SKF 38393, increased the frequency of locomotor-related bursting induced by 5-hydroxytryptamine and N-methyl-d-aspartate. Bath-applied adenosine reduced burst frequency only in the presence of SKF 38393, as did adenosine produced after activation of protease-activated receptor-1 to stimulate astrocytes. Furthermore, the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine enhanced burst frequency only in the presence of SKF 38393, indicating that endogenous adenosine produced by astrocytes during network activity also acts by modulating D1LR signaling. Finally, modulation of bursting by adenosine released upon stimulation of astrocytes was blocked by protein kinase inhibitor-(14–22) amide, a protein kinase A (PKA) inhibitor, consistent with A1R-mediated antagonism of the D1LR/adenylyl cyclase/PKA pathway. Together, these findings support a novel, astrocytic mechanism of metamodulation within the mammalian spinal cord, highlighting the complexity of the molecular interactions that specify motor output. NEW & NOTEWORTHY Astrocytes within the spinal cord produce adenosine during ongoing locomotor-related activity or when experimentally stimulated. Here, we show that adenosine derived from astrocytes acts at A1 receptors to inhibit a pathway by which D1-like receptors enhance the frequency of locomotor-related bursting. These data support a novel form of metamodulation within the mammalian spinal cord, enhancing our understanding of neuron-astrocyte interactions and their importance in shaping network activity.



1989 ◽  
Vol 9 ◽  
pp. 141
Author(s):  
Muneyasu Shirouzu ◽  
Takehiko Anraku ◽  
Yoshifumi Iwashita ◽  
Masami Yoshida


1996 ◽  
Vol 714 (1-2) ◽  
pp. 177-184 ◽  
Author(s):  
Wilhelm Nacimiento ◽  
Bernd Schlözer ◽  
Gary A. Brook ◽  
Lajos Tóth ◽  
Rudolf Töpper ◽  
...  




1993 ◽  
Vol 69 (4) ◽  
pp. 1338-1349 ◽  
Author(s):  
L. Ziskind-Conhaim ◽  
B. S. Seebach ◽  
B. X. Gao

1. Motoneuron responses to serotonin (5-hydroxytryptamine, 5-HT), and the growth pattern of 5-HT projections into the ventral horn were studied in the isolated spinal cord of embryonic and neonatal rats. 2. 5-HT projections first appeared in lumbar spinal cord at days 16-17 of gestation (E16-E17) and were localized in the lateral and ventral funiculi. By E18, the projections had grown into the ventral horn, and at 1-2 days after birth they were in close apposition to motoneuron somata. 3. At E16-E17, slow-rising depolarizing potentials of 1-4 mV were recorded intracellularly in lumbar motoneurons in response to bath application of 5-HT. These potentials were not apparent after E18; at that time 5-HT generated long-lasting depolarizations with an average amplitude of 6 mV, and an increase of 11% in membrane resistance. Starting at E18, 5-HT also induced high-frequency fast-rising potentials that were blocked by antagonists of glutamate, gamma-aminobutyric acid, and glycine. 4. Motoneuron responses to 5-HT increased significantly after birth, when 5-HT produced an average depolarization of 19 mV and repetitive firing of action potentials. 5. Tetrodotoxin and high Mg2+ did not reduce the amplitude of the long-lasting depolarizations, which suggested that they were produced by direct action of 5-HT on motoneuron membrane. 6. At all developmental ages, 5-HT reduced the amplitude of dorsal root-evoked potentials. The suppressed responses were neither due to 5-HT-induced depolarization nor the result of a decrease in motoneuron excitability. 7. The pharmacological profile of 5-HT-induced potentials was studied with the use of various agonists and antagonists of 5-HT. The findings indicated that the actions of 5-HT on spinal neurons were mediated via multiple 5-HT receptor subtypes. 8. Our results suggested that 5-HT excited spinal neurons before 5-HT projections grew into the ventral horn. The characteristics of 5-HT-induced potentials changed, however, at the time when the density of 5-HT projections increased in the motor nuclei.



2006 ◽  
Vol 96 (5) ◽  
pp. 2670-2677 ◽  
Author(s):  
Morten Smith ◽  
Jean-François Perrier

Interneurons in the ventral horn of the spinal cord play a central role in motor control. In adult vertebrates, their intrinsic properties are poorly described because of the lack of in vitro preparations from the spinal cord of mature mammals. Taking advantage of the high resistance to anoxia in the adult turtle, we used a slice preparation from the spinal cord. We used the whole cell blind patch-clamp technique to record from ventral horn interneurons. We characterized their firing patterns in response to depolarizing current pulses and found that all the interneurons fired repetitively. They displayed bursting, adapting, delayed, accelerating, or oscillating firing patterns. By combining electrophysiological and pharmacological tests, we showed that interneurons expressed slow inward rectification, plateau potential, voltage-sensitive transient outward rectification, and low-threshold spikes. These results demonstrate a diversity of intrinsic properties that may enable a rich repertoire of activity patterns in the network of ventral horn interneurons.



2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Rong Hu ◽  
Haipeng Xu ◽  
Yaheng Jiang ◽  
Yi Chen ◽  
Kelin He ◽  
...  

Peripheral nerve networks (PNNs) play a vital role in the neural recovery after spinal cord injury (SCI). Electroacupuncture (EA), as an alternative medicine, has been widely used in SCI and was proven to be effective on neural functional recovery. In this study, the interaction between PNNs and semaphrin3A (Sema3A) in the recovery of the motor function after SCI was observed, and the effect of EA on them was evaluated. After the establishment of the SCI animal model, we found that motor neurons in the ventral horn of the injured spinal cord segment decreased, Nissl bodies were blurry, and PNNs and Sema3A as well as its receptor neuropilin1 (NRP1) aggregated around the central tube of the gray matter of the spinal cord. When we knocked down the expression of Sema3A at the damage site, NRP1 also downregulated, importantly, PNNs concentration decreased, and tenascin-R (TN-R) and aggrecan were also reduced, while the Basso-Beattie-Bresnahan (BBB) motor function score dramatically increased. In addition, when conducting EA stimulation on Jiaji (EX-B2) acupoints, the highly upregulated Sema3A and NRP1 were reversed post-SCI, which can lessen the accumulation of PNNs around the central tube of the spinal cord gray matter, and simultaneously promote the recovery of motor function in rats. These results suggest that EA may further affect the plasticity of PNNs by regulating the Sema3A signal and promoting the recovery of the motor function post-SCI.



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