scholarly journals Spinal V3 interneurons and left-right coordination in mammalian locomotion

2019 ◽  
Author(s):  
Simon M. Danner ◽  
Han Zhang ◽  
Natalia A. Shevtsova ◽  
Joanna Borowska ◽  
Ilya A. Rybak ◽  
...  

AbstractCommissural interneurons (CINs) mediate interactions between rhythm-generating locomotor circuits located on each side of the spinal cord and are necessary for left-right limb coordination during locomotion. While glutamatergic V3 CINs have been implicated in left-right coordination, their functional connectivity remains elusive. Here, we addressed this issue by combining experimental and modeling approaches. We employed Sim1Cre/+; Ai32 mice, in which light-activated Channelrhodopsin-2 was selectively expressed in V3 interneurons. Fictive locomotor activity was evoked by NMDA and 5-HT in the isolated neonatal lumbar spinal cord. Flexor and extensor activities were recorded from left and right L2 and L5 ventral roots, respectively. Bilateral photoactivation of V3 interneurons increased the duration of extensor bursts resulting in a slowed down on-going rhythm. At high light intensities, extensor activity could become sustained. When light stimulation was shifted toward one side of the cord, the duration of extensor bursts still increased on both sides, but these changes were more pronounced on the contralateral side than on the ipsilateral side. Additional bursts appeared on the ipsilateral side not seen on the contralateral side. Further increase of the stimulation could suppress the contralateral oscillations by switching to a sustained extensor activity, while the ipsilateral rhythmic activity remained. To delineate the function of V3 interneurons and their connectivity, we developed a computational model of the spinal circuits consisting of two (left and right) rhythm generators (RGs) interacting via V0V, V0D and V3 CINs. Both types of V0 CINs provided mutual inhibition between the left and right flexor RG centers and promoted left-right alternation. V3 CINs mediated mutual excitation between the left and right extensor RG centers. These interactions allowed the model to reproduce our current experimental data, while being consistent with previous data concerning the role of V0V and V0D CINs in securing left-right alternation and the changes in left-right coordination following their selective removal. We suggest that V3 CINs provide mutual excitation between the spinal neurons involved in the control of left and right extensor activity, which may promote left-right synchronization during locomotion.


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.



1984 ◽  
Vol 52 (3) ◽  
pp. 449-458 ◽  
Author(s):  
A. R. Light ◽  
R. G. Durkovic

Single-unit recordings from 312 units of lamina I-VII of the lumbar spinal cord of unanesthetized, decerebrate, T8 spinal cats were used to determine the somatotopic and laminar organization of spinal neurons responding to cutaneous stimulation of the hindlimb. Properties of cells confined to different Rexed laminae (I-VII) were shown to differ in several respects, including responses to variations in stimulus intensity, receptive-field areas, spontaneous frequencies, and central delays. Spinal cord neurons with similarly localized cutaneous receptive fields were found to be organized in sagittally oriented rectangular columns. These columns were 7 to at least 20 mm long (rostral-caudal axis), 0.5-1.0 mm wide, and could encompass laminae I-VII in depth. Touch, pressure, and pinch were effective excitatory inputs into each column subserving a given receptive-field location. A map of the somatotopic organization of units in the horizontal plane is presented, which in general confirms previous reports and in particular deals with the organization of units with receptive fields on the plantar cushion and individual toes.



Neurosurgery ◽  
1979 ◽  
Vol 4 (2) ◽  
pp. 152-156 ◽  
Author(s):  
J. E. Smith ◽  
P. V. Hall ◽  
M. R. Galvin ◽  
A. R. Jones ◽  
R. L. Campbell

Abstract Twelve female mongrel dogs were made paraplegic by midthoracic spinal cord transection. Beginning at 9 weeks posttransection, either glycine (50 mg/kg) or saline was injected intramuscularly each day and the signs of spinal spasticity were assessed clinically. After treating the dogs for 3 weeks, we removed the lumbar enlargement of each dog and microdissected it into gray and white areas which we assayed for glycine, glutamate, and aspartate content. Some of the clinical signs of spasticity improved in the animals injected with glycine compared to the saline-injected controls. The content of glycine was significantly elevated in the central gray matter and ventral medial white matter of the glycinetreated dogs. The levels of glutamate were also significantly elevated in the central, lateral ventral, and medial ventral gray matter and in the dorsal lateral and ventral medial white matter of the glycine-treated dogs. The possible role of these segmental putative neurotransmitters in spinal spasticity is discussed.



2018 ◽  
Vol 1695 ◽  
pp. 78-83 ◽  
Author(s):  
Olga Kononenko ◽  
Irina Mityakina ◽  
Vladimir Galatenko ◽  
Hiroyuki Watanabe ◽  
Igor Bazov ◽  
...  


2002 ◽  
Vol 87 (2) ◽  
pp. 1094-1105 ◽  
Author(s):  
Rezan Demir ◽  
Bao-Xi Gao ◽  
Meyer B. Jackson ◽  
Lea Ziskind-Conhaim

Neural networks capable of generating coordinated rhythmic activity form at early stages of development in the spinal cord. In this study, voltage-imaging techniques were used to examine the spatiotemporal pattern of rhythmic activity in transverse slices of lumbar spinal cord from embryonic and neonatal rats. Real-time images were recorded in slices stained with the voltage-sensitive fluorescent dye RH414 using a 464-element photodiode array. Fluorescence signals showed spontaneous voltage oscillations with a frequency of 3 Hz. Simultaneous recordings of fluorescence and extracellular field potential demonstrated that the two signals oscillated with the same frequency and had a distinct phase relationship, indicating that the fluorescence changes represented changes in transmembrane potentials. The oscillations were reversibly blocked by cobalt (1 mM), indicating a dependence on Ca2+ influx through voltage-gated Ca2+ channels. Extracellular field potentials revealed oscillations with the same frequency in both stained and unstained slices. Oscillations were apparent throughout a slice, although their amplitudes varied in different regions. The largest amplitude oscillations were produced in the lateral regions. To examine the spatial organization of rhythm-generating networks, slices were cut into halves and quarters. Each fragment continued to oscillate with the same frequency as intact slices but with smaller amplitudes. This finding suggested that rhythm-generating networks were widely distributed and did not depend on long-range projections. In slices from neonatal rats, the oscillations exhibited a complex spatiotemporal pattern, with depolarizations alternating between mirror locations in the right and left sides of the cord. Furthermore, within each side depolarizations alternated between the lateral and medial regions. This medial-lateral pattern was preserved in hemisected slices, indicating that pathways intrinsic to each side coordinated this activity. A different pattern of oscillation was observed in slices from embryos with synchronous 3-Hz oscillations occurring in limited regions. Our study demonstrated that rhythm generators were distributed throughout transverse sections of the lumbar spinal cord and exhibited a complex spatiotemporal pattern of coordinated rhythmic activity.





1990 ◽  
Vol 64 (1) ◽  
pp. 299-311 ◽  
Author(s):  
V. Neugebauer ◽  
H. G. Schaible

1. In the spinalized cat, nociceptive spinal neurons with knee input show enhanced responses to mechanical stimulation of that joint once an inflammation has developed in the knee. Enhanced responses may result from increased afferent inflow as well as from modifications of the nociceptive processing within the spinal cord. To examine the significance of these components, we tested in 30 chloralose-anesthetized, spinalized cats whether, during development of arthritis, changes of responsiveness in spinal neurons are restricted to stimulation of the inflamed joint or whether responsiveness in these neurons is altered in general. While continuously recording from a neuron, we injected kaolin and carrageenan into one knee and tested the responses to mechanical stimuli applied to the joint and to regions adjacent to and remote from the knee during the developing arthritis. In addition, in six cats we monitored the neurons' responses to electrical stimulation of the sural nerves and the rostral lumbar spinal cord. 2. Of 32 neurons in laminae VI, VII, and VIII of the lumbar spinal cord, 15 ascending and eight nonascending cells were driven by mechanical stimulation of one or both knee joint(s). Nine of these were nociceptive specific (NS), responding exclusively or predominantly to noxious compression of the knee and other deep tissue, and 12 were wide-dynamic-range (WDR) cells with graded responses to gentle and noxious stimuli applied to the knee joint(s), deep tissue, and skin. Two neurons with high ongoing discharges had some excitatory joint input but showed marked inhibition by most stimuli used (INH neurons). The majority of the neurons had receptive fields on both legs. Nine of the 32 neurons had no input from the knee(s). 3. All 23 neurons with joint input became sensitive or more responsive to movements and gentle compression of the inflamed knee once the inflammation had developed. In general, these neurons also showed enhanced responses to compression of the adjacent muscles in thigh and lower leg. In 20 neurons, response properties were even altered for stimuli applied to regions remote from the inflamed joint, including the contralateral leg in 18 cases. We found expansion of initially restricted receptive fields (mainly in NS cells), enhancement of preexisting responses, and/or lowering of threshold to mechanical stimuli applied to these regions; few neurons developed inhibitory reactions.(ABSTRACT TRUNCATED AT 400 WORDS)



2001 ◽  
Vol 86 (5) ◽  
pp. 2276-2284 ◽  
Author(s):  
Takahiko Mitsui ◽  
Hidehiro Kakizaki ◽  
Shinobu Matsuura ◽  
Kaname Ameda ◽  
Mitsuhiro Yoshioka ◽  
...  

To evaluate the role of bladder afferent fibers in the hypogastric nerves (HGN) in modulation of the micturition reflex induced by chemical bladder irritation, voiding behavior, continuous cystometry, and spinal c-fos expression following intravesical acetic acid instillation were investigated in rats with or without HGN transection. Voiding behavior and continuous cystometry were examined in unanesthetized conscious rats. Following chemical bladder irritation, a significant increase in urinary frequency associated with a marked decrease in the voided volume per micturition, was noted in control rats with the intact HGN, but not in HGN-transected rats. Continuous infusion of acetic acid in control rats elicited irritative bladder responses characterized by a marked decrease in the intercontraction interval and a marked increase in maximal vesical pressure, both of which were absent in capsaicin-desensitized rats. HGN transection prevented the decrease in the intercontraction interval but not an increase in maximal vesical pressure following chemical bladder irritation. Compared with saline infusion, acetic acid infusion caused a significant increase in c-fos expression at L1 and L6 of the spinal cord, and HGN transection significantly reduced c-fos expression in the dorsal horn of the spinal cord at L1 but not at L6. These results suggest that capsaicin-sensitive bladder afferent fibers in the HGN, which travel through the rostral lumbar spinal cord, have a role in urinary frequency caused by chemical bladder irritation.



2017 ◽  
Vol 11 ◽  
Author(s):  
Carlos A. Cuellar ◽  
Aldo A. Mendez ◽  
Riazul Islam ◽  
Jonathan S. Calvert ◽  
Peter J. Grahn ◽  
...  


2007 ◽  
Vol 292 (3) ◽  
pp. R1368-R1375 ◽  
Author(s):  
Li-Ya Qiao ◽  
Melisa A. Gulick

Chronic inflammation of the urinary bladder generates hyperalgesia and allodynia. Growing evidence suggests a role of ERK in mediating somatic and visceral pain processing. In the present studies, we characterized and compared the activation of two ERK isoforms, ERK1/2 and ERK5, in micturition pathways, including the urinary bladder, lumbosacral dorsal root ganglia (DRG), and spinal cord in adult female and male rats before and after cyclophosphamide (CYP)-induced bladder inflammation. Results showed differential activation of ERK1/2 and ERK5 in these regions following cystitis. The level of phospho-ERK1/2 but not phospho-ERK5 was increased in the urinary bladder; the level of phospho-ERK5 but not phospho-ERK1/2 was increased in DRG; and the level of phospho-ERK1/2 but not phospho-ERK5 was increased in lumbar spinal cord following cystitis compared with control. Cystitis-induced upregulation of phospho-ERK1/2 and phospho-ERK5 was time dependent and showed similar patterns in female and male rats. The level of phospho-ERK1/2 in bladder was increased at 2 and 8 h after CYP injection; the level of phospho-ERK5 in DRG was increased at 8 and 48 h after CYP injection; and the level of phospho-ERK1/2 in lumbar spinal cord was increased at 48 h after CYP injection. The result that phospho-ERK5 was exclusively increased in DRG neurons, while phospho-ERK1/2 was increased in the spinal cord and the urinary bladder after cystitis, suggests a region-specific effect of neurotrophins on micturition pathways following bladder inflammation.



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