Beginning at the end: Repetitive firing properties in the final common pathway

Brownstone, Robert M.

doi:10.1016/j.pneurobio.2006.04.002

Cited by 84 publications

(59 citation statements)

References 178 publications

(216 reference statements)

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“…For example, in cross-reinnervation studies, the contractile and biochemical properties of muscle fibers change to match the firing patterns of the reinnervating MN [i.e., slow MNs convert type II to type I muscle fibers (Buller et al, 1960;Luff, 1975;Bagust et al, 1981)]. Thus the increase in type I fibers in this study may be attributable to the fact that the ES-cell-derived MNs were tonically active at low firing rates, either because of synaptic connectivity between interneurons and MNs within the graft site (Miles et al, 2004), or because of their intrinsic properties, which are similar to those of slow MNs (Brownstone, 2006;Soundararajan et al, 2006). Alternatively, preliminary evidence suggests that activity may be movement related, perhaps caused by mechanical stimulation by surrounding tissue (supplemental Fig.…”

Section: Discussionmentioning

confidence: 82%

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Yohn¹,

Miles²,

Rafuse³

et al. 2008

J. Neurosci.

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Prolonged muscle denervation resulting from motor neuron (MN) damage leads to atrophy and degeneration of neuromuscular junctions (NMJs), which can impart irreversible damage. In this study, we ask whether transplanted embryonic stem (ES) cells differentiated into MNs can form functional synapses with host muscle, and if so what effects do they have on the muscle. After transplantation into transected tibial nerves of adult mice, ES-cell-derived MNs formed functional synapses with denervated host muscle, which resulted in the ability to produce average tetanic forces of 44% of nonlesioned controls. ES-cell-derived motor units (MUs) had mean force values and ranges similar to control muscles. The number of type I fibers and fatigue resistance of the MUs were increased, and denervationassociated muscle atrophy was significantly reduced. These results demonstrate the capacity for ES-cell-derived MNs not only to incorporate into the adult host tissue, but also to exert changes in the target tissue. By providing the signals normally active during embryonic development and placing the cells in an environment with their target tissue, ES cells differentiate into MNs that give rise to functional MU output which resembles the MU output of endogenous MNs. This suggests that these signals combined with those present in the graft environment, lead to the activation of a program intended to produce a normal range of MU forces.

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Section: Discussionmentioning

confidence: 82%

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Yohn¹,

Miles²,

Rafuse³

et al. 2008

J. Neurosci.

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“…Thus, it is important to measure the firing rate of the control unit during periods of linear input-output which likely occurs during moderate rates of discharge (5–20 Hz) and durations of spike trains (10–20 s), to avoid firing rate saturation and adaptation, respectively (Sawczuk et al, 1997; Brownstone, 2006). These values are based on firing rate properties of sacral rat motoneurons that are similar to firing properties of human motor units in the lower limb (Li et al, 2004a).…”

Section: Changes In Motoneuron Properties After Scimentioning

confidence: 99%

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

D’Amico

Condliffe

Martins

et al. 2014

Front. Integr. Neurosci.

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The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI.

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“…6) suggests that these phenomena share common mechanisms. The mechanism of firing rate adaptation is as yet unknown, but is likely to involve a gradual decrease in inward current (e.g., increased inactivation of transient or persistent sodium channels) and/or increase in outward current (e.g., increased calcium-dependent potassium current that contributes to the AHP) (Brownstone 2006;Miles et al 2005;Powers et al 1999;Schwindt and Crill 1982). PICs mediated by sodium ions exhibit preferential inactivation in high-rheobase motoneurons (Lee and Heckman 2001).…”

Section: Expression Of Pics In Eus Motoneuronsmentioning

confidence: 99%

External Urethral Sphincter Motoneuron Properties in Adult Female Rats Studied In Vitro

Carp

Tennissen

Liebschutz

et al. 2010

Journal of Neurophysiology

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Carp JS, Tennissen AM, Liebschutz JE, Chen XY, Wolpaw JR. External urethral sphincter motoneuron properties in adult female rats studied in vitro. J Neurophysiol 104: 1286 -1300, 2010. First published June 23, 2010 doi:10.1152/jn.00224.2010. The external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate ϭ 12-27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulatorindependent mechanisms. I N T R O D U C T I O NThe external urethral sphincter (EUS) muscle performs the critical function of restricting urinary flow through the urethra during continence and permitting flow during micturition. Much prior research has focused on how the brain controls spinal cord networks that operate this muscle and coordinate its function with the other muscles important in bladder control and on how peripheral input contributes to the control of lower urinary tract function (de Groat 2006).A full understanding of how descending and sensory inputs contribute to control of urethral function requires knowledge of how the EUS motoneuron integrates and transforms supraspinal motor commands, sensory inputs, and spinal interneuronal activity into sphincter muscle activity. The intrinsic properties of EUS motoneurons are similar in many ways to the much more extensively studied hindlimb motoneurons, but with specific differences tha...

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Beginning at the end: Repetitive firing properties in the final common pathway

Cited by 84 publications

References 178 publications

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

External Urethral Sphincter Motoneuron Properties in Adult Female Rats Studied In Vitro

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