Modulation of motoneuron firing by recurrent inhibition in the adult rat in vivo

Obeidat, Ahmed Z.; Nardelli, Paul; Powers, Randall K.; Cope, Timothy C.

doi:10.1152/jn.00358.2014

Cited by 10 publications

(12 citation statements)

References 88 publications

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“…; Liu & Bean, ; Obeidat et al . ). Because STX application does not alter the single isolated action potential, the results presented herein are not likely to be a confounding effect of STX acting directly upon Na + channels.…”

Section: Discussionmentioning

confidence: 97%

A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons

Romer

Deardorff

Fyffe

2019

The Journal of Physiology

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Key points Kv2 currents maintain and regulate motoneuron (MN) repetitive firing properties. Kv2.1 channel clustering properties are dynamic and respond to both high and low activity conditions. The enzyme calcineurin regulates Kv2.1 ion channel declustering. In patholophysiological conditions of high activity, Kv2.1 channels homeostatically reduce MN repetitive firing. Modulation of Kv2.1 channel kinetics and clustering allows these channels to act in a variable way across a spectrum of MN activity states. Abstract Kv2.1 channels are widely expressed in the central nervous system, including in spinal motoneurons (MNs) where they aggregate as distinct membrane clusters associated with highly regulated signalling ensembles at specific postsynaptic sites. Multiple roles for Kv2 channels have been proposed but the physiological role of Kv2.1 ion channels in mammalian spinal MNs is unknown. To determine the contribution of Kv2.1 channels to rat α‐motoneuron activity, the Kv2 inhibitor stromatoxin was used to block Kv2 currents in whole‐cell current clamp electrophysiological recordings in rat lumbar MNs. The results indicate that Kv2 currents permit shorter interspike intervals and higher repetitive firing rates, possibly by relieving Na+ channel inactivation, and thus contribute to maintenance of repetitive firing properties. We also demonstrate that Kv2.1 clustering properties in motoneurons are dynamic and respond to both high and low activity conditions. Furthermore, we show that the enzyme calcineurin regulates Kv2.1 ion channel clustering status. Finally, in a high activity state, Kv2.1 channels homeostatically reduce motoneuron repetitive firing. These results suggest that the activity‐dependent regulation of Kv2.1 channel kinetics allows these channels to modulate repetitive firing properties across a spectrum of motoneuron activity states.

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Section: Discussionmentioning

confidence: 97%

A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons

Romer

Deardorff

Fyffe

2019

The Journal of Physiology

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“…Similarly, it has been shown that Renshaw IPSP durations are shorter in firing MNs than those recorded at rest (Obeidat et al . ). This is exactly what was observed in the present study: the higher the discharge rate of the SMU, the shorter the RI duration.…”

Section: Discussionmentioning

confidence: 97%

Motor units as tools to evaluate profile of human Renshaw inhibition

Özyurt

Piotrkiewicz

Topkara

et al. 2019

The Journal of Physiology

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Key points To uncover the synaptic profile of Renshaw inhibition on motoneurons, we stimulated thick motor axons and recorded from voluntarily‐activated motor units. Stimuli generated a direct motor response on the whole muscle and an inhibitory response in active motor units. We have estimated the profile of Renshaw inhibition indirectly using the response of motor unit discharge rates to the stimulus. We have put forward a method of extrapolation that may be used to determine genuine synaptic potentials as they develop on motoneurons. These optimized techniques can be used in research and in clinics to fully appreciate Renshaw cell function in various neurological disorders. Abstract Although Renshaw inhibition (RI) has been extensively studied for decades, its precise role in motor control is yet to be discovered. One of the main handicaps is a lack of reliable methods for studying RI in conscious human subjects. We stimulated the lowest electrical threshold motor axons (thickest axons) in the tibial nerve and analysed the stimulus‐correlated changes in discharge of voluntarily recruited low‐threshold single motor units (SMUs) from the soleus muscle. In total, 54 distinct SMUs from 12 subjects were analysed. Stimuli that generated only the direct motor response (M‐only) on surface electromyography induced an inhibitory response in the low‐threshold SMUs. Because the properties of RI had to be estimated indirectly using the background discharge rate of SMUs, its profile varied with the discharge rate of the SMU. The duration of RI was found to be inversely proportional to the discharge rate of SMUs. Using this important finding, we have developed a method of extrapolation for estimating RI as it develops on motoneurons in the spinal cord. The frequency methods indicated that the duration of RI was between 30 and 40 ms depending on the background firing rate of the units, and the extrapolation indicated that RI on silent motoneurons was ∼55 ms. The present study establishes a novel methodology for studying RI in human subjects and hence may serve as a tool for improving our understanding of the involvement of RI in human motor control.

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“…Experiments proceeded with one of the terminal studies described below. Optimal parameters for nerve stimulation were set with the following considerations: (a) stimulus frequency (100 Hz) approximates the upper limit of the MN firing rate in anesthetized rats Turkin et al, 2010;Obeidat et al 2014); and (b) stimulus strength (4X MG contraction threshold) maximally activates large diameter axons, including motor axons and Group I/II afferents (Bichler et al 2007b;Bullinger et al 2011b).…”

Section: In Vivo Sciatic Stimulationmentioning

confidence: 99%

Activity-dependent redistribution of Kv2.1 ion channels on rat spinal motoneurons

2016

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Homeostatic plasticity occurs through diverse cellular and synaptic mechanisms, and extensive investigations over the preceding decade have established Kv2.1 ion channels as key homeostatic regulatory elements in several central neuronal systems. As in these cellular systems, Kv2.1 channels in spinal motoneurons (MNs) localize within large somatic membrane clusters. However, their role in regulating motoneuron activity is not fully established in vivo. We have previously demonstrated marked Kv2.1 channel redistribution in MNs following in vitro glutamate application and in vivo peripheral nerve injury (Romer et al., 2014, Brain Research, 1547:1–15). Here, we extend these findings through the novel use of a fully intact, in vivo rat preparation to show that Kv2.1 ion channels in lumbar MNs rapidly and reversibly redistribute throughout the somatic membrane following 10 min of electrophysiological sensory and/or motor nerve stimulation. These data establish that Kv2.1 channels are remarkably responsive in vivo to electrically evoked and synaptically driven action potentials in MNs, and strongly implicate motoneuron Kv2.1 channels in the rapid homeostatic response to altered neuronal activity.

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Modulation of motoneuron firing by recurrent inhibition in the adult rat in vivo

Cited by 10 publications

References 88 publications

A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons

A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons

Motor units as tools to evaluate profile of human Renshaw inhibition

Activity-dependent redistribution of Kv2.1 ion channels on rat spinal motoneurons

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