Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches

Larry M. Jordan, J. R. McVagh, Brian R Noga, A. M. Cabaj, H. Majczyński, Urszula Sławińska, J. Provencher, H. Leblond, Serge Rossignol

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.

Original languageEnglish
Article number132
JournalFrontiers in Neural Circuits
Volume8
DOIs
StatePublished - Nov 6 2014

Fingerprint

Locomotion
Cholinergic Agents
Rehabilitation
Spinal Cord Injuries
Cholinergic Antagonists
Motor Neurons
Brain Stem
Muscarinic M3 Receptors
Muscarinic M2 Receptors
Cholinergic Agonists
Clonidine
Cats
Extremities

Keywords

  • Cholinergic mechanisms
  • Chronic spinal cat
  • Chronic spinal rat
  • Decerebrate cat
  • In vitro neonatal rat
  • Spinal rhythm generation

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience
  • Sensory Systems
  • Cognitive Neuroscience

Cite this

Jordan, L. M., McVagh, J. R., Noga, B. R., Cabaj, A. M., Majczyński, H., Sławińska, U., ... Rossignol, S. (2014). Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches. Frontiers in Neural Circuits, 8, [132]. https://doi.org/10.3389/fncir.2014.00132

Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches. / Jordan, Larry M.; McVagh, J. R.; Noga, Brian R; Cabaj, A. M.; Majczyński, H.; Sławińska, Urszula; Provencher, J.; Leblond, H.; Rossignol, Serge.

In: Frontiers in Neural Circuits, Vol. 8, 132, 06.11.2014.

Research output: Contribution to journalArticle

Jordan, LM, McVagh, JR, Noga, BR, Cabaj, AM, Majczyński, H, Sławińska, U, Provencher, J, Leblond, H & Rossignol, S 2014, 'Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches', Frontiers in Neural Circuits, vol. 8, 132. https://doi.org/10.3389/fncir.2014.00132
Jordan, Larry M. ; McVagh, J. R. ; Noga, Brian R ; Cabaj, A. M. ; Majczyński, H. ; Sławińska, Urszula ; Provencher, J. ; Leblond, H. ; Rossignol, Serge. / Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches. In: Frontiers in Neural Circuits. 2014 ; Vol. 8.
@article{8eb9796be65e4d2785c68e070c6a5816,
title = "Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches",
abstract = "Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.",
keywords = "Cholinergic mechanisms, Chronic spinal cat, Chronic spinal rat, Decerebrate cat, In vitro neonatal rat, Spinal rhythm generation",
author = "Jordan, {Larry M.} and McVagh, {J. R.} and Noga, {Brian R} and Cabaj, {A. M.} and H. Majczyński and Urszula Sławińska and J. Provencher and H. Leblond and Serge Rossignol",
year = "2014",
month = "11",
day = "6",
doi = "10.3389/fncir.2014.00132",
language = "English",
volume = "8",
journal = "Frontiers in Neural Circuits",
issn = "1662-5110",
publisher = "Frontiers Research Foundation",

}

TY - JOUR

T1 - Cholinergic mechanisms in spinal locomotion — Potential target for rehabilitation approaches

AU - Jordan, Larry M.

AU - McVagh, J. R.

AU - Noga, Brian R

AU - Cabaj, A. M.

AU - Majczyński, H.

AU - Sławińska, Urszula

AU - Provencher, J.

AU - Leblond, H.

AU - Rossignol, Serge

PY - 2014/11/6

Y1 - 2014/11/6

N2 - Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.

AB - Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.

KW - Cholinergic mechanisms

KW - Chronic spinal cat

KW - Chronic spinal rat

KW - Decerebrate cat

KW - In vitro neonatal rat

KW - Spinal rhythm generation

UR - http://www.scopus.com/inward/record.url?scp=84908621800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908621800&partnerID=8YFLogxK

U2 - 10.3389/fncir.2014.00132

DO - 10.3389/fncir.2014.00132

M3 - Article

VL - 8

JO - Frontiers in Neural Circuits

JF - Frontiers in Neural Circuits

SN - 1662-5110

M1 - 132

ER -