Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2009 Apr 29;29(17):5681-9.
doi: 10.1523/JNEUROSCI.6058-08.2009.

Propriospinal bypass of the serotonergic system that can facilitate stepping

Yury Gerasimenko  1 , Pavel Musienko, Irina Bogacheva, Tatiana Moshonkina, Alexandr Savochin, Igor Lavrov, Roland R Roy, V Reggie Edgerton
Affiliations
Comparative Study

Propriospinal bypass of the serotonergic system that can facilitate stepping

Yury Gerasimenko et al. J Neurosci. .

Abstract

The neurotransmitter systems mediating spinal locomotion in response to epidural spinal cord stimulation (ES) have not been identified. Here, we examine the role of the serotonergic system in regulating locomotor behavior of decerebrated cats during ES at L4-L5. ES elicited coordinated, weight-bearing, hindlimb stepping with plantar foot placement on a moving treadmill belt. Ketanserin [a 5-hydroxytryptamine (serotonin) (5-HT)(2/7) receptor antagonist] depressed this locomotor activity: only weak rhythmic movements without plantar foot placement and depressed EMG activity were observed. Cyproheptadine, a nonselective 5-HT blocker, prevented facilitation of stepping by epidural stimulation. These data demonstrate an important role of the serotonergic system in facilitating locomotion in the presence of epidural stimulation. In the presence of ketanserin, passive movements of one forelimb in a step-like manner immediately induced stepping of both hindlimbs with EMG patterns similar to those observed with ES without ketanserin. Thus, a non-5-HT-dependent spinal circuitry projecting from the cervical to the lumbar region of the spinal cord can facilitate stepping. The specific neurotransmitters responsible for this forelimb-facilitated stepping of the hindlimbs are unknown. These data suggest that a 5-HT(2/7) receptor-dependent pathway that processes hindlimb locomotor-like proprioception to facilitate hindlimb stepping can be complemented with proprioceptive afferents from the forelimbs via a non-5-HT(2/7) receptor neurotransmitter system. Thus, different neurotransmitter receptor systems can be used to mediate the same type of sensory event, i.e., locomotor-like proprioception to facilitate the same motor task, i.e., hindlimb stepping.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Effects of ketanserin (K) on the stepping pattern induced by ES in decerebrated cats. EMG recordings from the left VL (LVL), left St (LSt), left LG (LLG), left TA (LTA), right LG (RLG), and right TA (RTA) muscles during stepping at a belt speed of 0.3–0.4 m/s induced by ES alone (A) or by ES plus K administration (ES+K) (B). Note that the administration of K markedly reduces the EMG bursting in all muscles. C, Videographic recordings of one step cycle on the treadmill at a belt speed of 0.3–0.4 m/s during ES and ES+K are shown. Note the robust step kinematics induced by ES, whereas little movement of the limb is observed after K administration. D, Change of mean amplitude of the EMG bursts and the mean EMG burst duration in VL, St, LG, and TA of the left hindlimb during ES after administration of K relative to that seen for ES alone are shown. *p < 0.05, significant difference between ES alone and ES+K.
Figure 2.
Figure 2.
EMG activity recorded in the hindlimb muscles of a decerebrated cat during stepping with ES (at 5 Hz) and after the cessation of ES. Stepping data are recorded during ES alone (A), ES in the presence of K (B), and ES in the presence of K plus passive forelimb (FL) movements (C). Note that the administration of K decreases the EMG bursting activity during and after the cessation of ES compared with the ES alone condition (compare B with A). Passive FL movements under the ES+K condition restored the EMG activity to that observed with ES alone (compare C with A). Abbreviations, same as in Figure 1.
Figure 3.
Figure 3.
Effects of cyproheptadine on the EMG activity induced by ES. EMG activity in the LVL and RLG during ES alone (A), ES in the presence of cyproheptadine (B), and ES in the presence of cyproheptadine plus forelimb movements (C) are shown. Note the inhibition of EMG activity by cyproheptadine administration and the recovery of activity with FL movement. Abbreviations, same as in Figures 1 and 2.
Figure 4.
Figure 4.
Presence of an SLP and LLC in the VL EMG burst induced by ES (5 Hz) during stepping in a decerebrated cat. The shaded region in the top trace is expanded in the bottom trace. The vertical arrows in the bottom trace indicate the time frames for the SLP (1–25 ms) and the LLC (26–196 ms) responses. Artifacts of ES are shown on the second line.
Figure 5.
Figure 5.
Superposition of four responses within a single VL EMG burst during ES alone, ES+K, and ES+K+FL are shown in A. The mean integral (expressed as a percentage of pre-K administration) of the SLP and LLC within the VL, St, LG, and TA EMG bursts during stepping with ES+K, ES+K+FL as well as during ES ∼2–2.5 h after K administration (ES recovery) are shown in B. Note the significantly smaller responses under ES+K, the partial recovery with FL movements, and the restoration of the responses to or above pre-K values after recovery. Significant difference between ES+K and ES+K+FL at *p < 0.05. In all cases, ES recovery is significantly different from ES+K. In C, the percentage change in the integral of the SLP and LLC for each of four animals. All data are collected from muscles on the same side. Each symbol represents the same animal for each of the four muscles. Abbreviations, same as in Figures 1 and 2.
Figure 6.
Figure 6.
Effect of quality of forelimb movements in a decerebrate cat on stepping performance of the hindlimbs during ES in the presence of K. EMG recordings in the LBB, LTB, LVL, and RLG during ES-induced stepping in the presence of K plus air stepping (A) or weight-bearing stepping on a treadmill (B). The mean cycle period, mean EMG burst duration, and mean integrated area of the rectified EMG burst of the LVL and RLG during air stepping or weight-bearing stepping induced by ES and in presence of K are shown in C. Note the more robust EMG bursts in both the forelimb and hindlimb muscles during weight-bearing than during air stepping. Significantly different at *p < 0.05. Abbreviations, same as in Figures 1 and 2.
Figure 7.
Figure 7.
Averaged (n = 10) SLPs from the LLG and LTA in response to ES (0.3 Hz) during standing in two decerebrated cats (A, B) are shown. The gray traces show the potentials before and the black traces after ketanserin administration. Note the lower (∼50%) amplitudes after rather than before ketanserin administration. Abbreviations, same as in Figures 1 and 2.
Figure 8.
Figure 8.
Hypothetical blocks at the motoneurons and/or at the interneurons are illustrated. Robust hindlimb locomotion (Locom) occurs during ES and when step-like sensory information is projected from the hindlimbs (HL) when they are placed on a moving treadmill belt. Ketanserin blocks this effect (−) (A). When one forelimb is moved in a step-like manner in the presence of a ketanserin block, the hindlimbs begin stepping almost immediately (+) (B). These results together demonstrate that those pathways through which the hindlimb sensory information and ES activate stepping are mediated via 5-HT2/7 receptors (X's), but sensory information from the forelimb can activate pathways that do not depend on 5-HT2/7 receptors (O's). A block at the level of interneurons may occur by activating different populations of interneurons or via the same population of interneurons having both 5-HT2/7 and non-5-HT2/7 receptors (B). Based on our current understanding of motor unit recruitment, the ketanserin block at the level of the motoneuron would probably occur as a result of the same motoneurons having both 5-HT2/7 and non-5-HT2/7 receptors. −, Suppression of hindlimb locomotion; +, facilitation of hindlimb locomotion; MN, motoneuron; IN, interneuron.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akay T, McVea DA, Tachibana A, Pearson KG. Coordination of fore and hind leg stepping in cats on a transversely-split treadmill. Exp Brain Res. 2006;175:211–222. - PubMed
    1. Antri M, Orsal D, Barthe JY. Locomotor recovery in the chronic spinal rat: effects of long-term treatment with a 5-HT2 agonist. Eur J Neurosci. 2002;16:467–476. - PubMed
    1. Ballion B, Morin D, Viala D. Forelimb locomotor generators and quadrupedal locomotion in the neonatal rat. Eur J Neurosci. 2001;14:1727–1738. - PubMed
    1. Barbeau H, Rossignol S. The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat. Brain Res. 1990;514:55–67. - PubMed
    1. Barbeau H, Rossignol S. Initiation and modulation of locomotor pattern in the adult chronic spinal cat by noradrenergic, serotonergic and dopaminergic drugs. Brain Res. 1991;546:250–260. - PubMed

Publication types