Serotonin Facilitates a Persistent Calcium Current in Motoneurons of Rats With and Without Chronic Spinal Cord Injury

Li, Xiaole; Murray, Katherine C.; Harvey, Philip J.; Ballou, Edmund W.; Bennett, D. J.

doi:10.1152/jn.00995.2006

Cited by 128 publications

(98 citation statements)

References 32 publications

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“…5-HT facilitates persistent inward current in spinal cord and vibrissa motoneurons (Cramer et al 2007;Li et al 2007) and it facilitates I NaP in mesencephalic and spinal motoneurons (Harvey et al 2006;Tanaka and Chandler 2006). In line with these reports we found that the induction of intrinsic spiking in spinal neurons by 5-HT goes in parallel with an increase in I NaP .…”

Section: -Ht Induces Intrinsic Spiking By Up-regulating I Nap Througsupporting

confidence: 88%

Modulation of Intrinsic Spiking in Spinal Cord Neurons

Czarnecki

Magloire

Streit

2009

Journal of Neurophysiology

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Czarnecki A, Magloire V, Streit J. Modulation of intrinsic spiking in spinal cord neurons. J Neurophysiol 102: 2441-2452, 2009. First published August 12, 2009 doi:10.1152/jn.00244.2009. The vertebrate spinal cord is equipped with a number of neuronal networks that underlie repetitive patterns of behavior as locomotion. Activity in such networks is mediated not only by intrinsic cellular properties but also by synaptic coupling. In this study, we focused on the modulation of the intrinsic activity by 5-hydroxytryptamine (5-HT, serotonin) and the cholinergic agonist muscarine in spinal cord cultures (embryonic age 14 rats). We investigated theses cultures (slices and dissociated cells) at the network level using multielectrode arrays (MEAs) and at the cellular level using whole cell patch clamp. All cultures showed bursting network activity and intrinsic activity when ␥-aminobutyric acid, glycine, and glutamate transmission was blocked. Using MEAs, we observed an increase of the intrinsic activity in the ventral part of the slices with 5-HT and muscarine. In single-cell recordings we found that 43 and 35% of the cells that were silent in the absence of fast synaptic activity were transformed into intrinsically spiking cells by 5-HT and muscarine, respectively. We tested the hypothesis that these neuromodulators act via modulation of the persistent sodium currents (I NaP ) in these neurons. We found that 5-HT increased threefold the amplitude of I NaP , specifically in the nonintrinsically spiking cells, and thus switched these cells into intrinsically spiking cells via activation of 5-HT 2 receptor and the phospholipase C pathway. In contrast, the effect of muscarine on nonintrinsically spiking neurons seems to be independent of I NaP . We conclude from these findings that serotoninergic and cholinergic modulation can turn silent into spontaneously spiking neurons and thus initiate new sources of activity for rhythm generation in spinal networks.

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Section: -Ht Induces Intrinsic Spiking By Up-regulating I Nap Througsupporting

confidence: 88%

Modulation of Intrinsic Spiking in Spinal Cord Neurons

Czarnecki

Magloire

Streit

2009

Journal of Neurophysiology

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“…In addition, it also possible that there is more NaP in cells with less preserved descending input as a result of an adaptation to the lack of this synaptic or neuromodulatory input. For example, recent studies have shown that PICs in chronic SCI models become supersensitive to serotonin (Harvey et al 2006a;Li et al 2007) and norepinephrine (Rank et al 2007). In more complete injuries, it is possible that cells with an increase in the loss of descending input compensate more with a higher degree of supersensitivity adaptation.…”

Section: Discussionmentioning

confidence: 99%

Riluzole decreases flexion withdrawal reflex but not voluntary ankle torque in human chronic spinal cord injury

Theiss

Hornby

Rymer

et al. 2011

Journal of Neurophysiology

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Theiss RD, Hornby TG, Rymer WZ, Schmit BD. Riluzole decreases flexion withdrawal reflex but not voluntary ankle torque in human chronic spinal cord injury. J Neurophysiol 105: 2781-2790, 2011. First published March 23, 2011 doi:10.1152/jn.00570.2010The objectives of this study were to probe the contribution of spinal neuron persistent sodium conductances to reflex hyperexcitability in human chronic spinal cord injury. The intrinsic excitability of spinal neurons provides a novel target for medical intervention. Studies in animal models have shown that persistent inward currents, such as persistent sodium currents, profoundly influence neuronal excitability, and recovery of persistent inward currents in spinal neurons of animals with spinal cord injury routinely coincides with the appearance of spastic reflexes. Pharmacologically, this neuronal excitability can be decreased by agents that reduce persistent inward currents, such as the selective persistent sodium current inhibitor riluzole. We were able to recruit seven subjects with chronic incomplete spinal cord injury who were not concurrently taking antispasticity medications into the study. Reflex responses (flexion withdrawal and H-reflexes) and volitional strength (isometric maximum voluntary contractions) were tested at the ankle before and after placebo-controlled, double-blinded oral administration of riluzole (50 mg). Riluzole significantly decreased the peak ankle dorsiflexion torque component of the flexion withdrawal reflex. Peak maximum voluntary torque in both dorsiflexion and plantarflexion directions was not significantly changed. Average dorsiflexion torque sustained during the 5-s isometric maximum voluntary contraction, however, increased significantly. There was no effect, however, on the monosynaptic plantar and dorsiflexor H-reflex responses. Overall, these results demonstrate a contribution of persistent sodium conductances to polysynaptic reflex excitability in human chronic spinal cord injury without a significant role in maximum strength production. These results suggest that intrinsic spinal cellular excitability could be a target for managing chronic spinal cord injury hyperreflexia impairments without causing a significant loss in volitional strength.

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“…In most studies, neuromodulators are shown to facilitate PICs (Hounsgaard et al, 1988b;Li et al, 2007). In the in vitro sacrocaudal spinal cord preparation of adult rat, monoamine receptor antagonists inhibit sodium PICs (Harvey et al, 2006a,b), indicating the presence of an endogenous source of monoamines.…”

Section: Discussionmentioning

confidence: 99%

Identified Ankle Extensor and Flexor Motoneurons Display Different Firing Profiles in the Neonatal Rat

Cotel

Antri²,

Barthe³

et al. 2009

J. Neurosci.

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The present study was designed to compare the firing profiles exhibited by lumbar flexor or extensor motoneurons in response to injection of depolarizing/repolarizing currents. Motoneurons were recorded intracellularly in the in vitro brainstem-spinal cord of newborn rats (P4 -P7). They were synaptically isolated and identified by antidromic stimulations of the central stump of flexor or extensor muscle nerves: tibialis anterior (ankle flexor) and gastrocnemius medialis or lateralis (ankle extensors). Two protocols were applied to establish the four firing profiles previously described (type I-IV) (Bennett et al., 2001): (1) symmetric depolarizing/repolarizing ramps of current and (2) progressive steps of depolarizing currents followed by equivalent steps of repolarizing current. According to such profiles, this study clearly shows that flexor and extensor motoneurons are different. The whole population of flexor motoneurons solely exhibited the type II profile, characterized by a frequency-current (F-I) relationship with a clockwise hysteresis. In contrast, in addition to this type II profile, the other three profiles of repetitive firing (type I, III and IV) were observed in extensor motoneurons; a linear F-I relationship (type I profile), a self-sustained discharge pattern together with a linear F-I relationship (type III profile) and a self-sustained firing pattern together with an F-I relationship showing a counter-clockwise hysteresis (type IV profile). Thus, during the early postnatal development, a significant part of the population of extensor motoneurons, but not flexors, are able to produce selfsustained discharges known to involve the activation of persistent inward currents.

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Serotonin Facilitates a Persistent Calcium Current in Motoneurons of Rats With and Without Chronic Spinal Cord Injury

Abstract: facilitates a persistent calcium current in motoneurons of rats with and without chronic spinal cord injury.

Cited by 128 publications

References 32 publications

Modulation of Intrinsic Spiking in Spinal Cord Neurons

Modulation of Intrinsic Spiking in Spinal Cord Neurons

Riluzole decreases flexion withdrawal reflex but not voluntary ankle torque in human chronic spinal cord injury

Identified Ankle Extensor and Flexor Motoneurons Display Different Firing Profiles in the Neonatal Rat

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