scholarly journals Estimation of self-sustained activity produced by persistent inward currents using firing rate profiles of multiple motor units in humans

2020 ◽  
Vol 124 (1) ◽  
pp. 63-85 ◽  
Author(s):  
Babak Afsharipour ◽  
Nagib Manzur ◽  
Jennifer Duchcherer ◽  
Keith F. Fenrich ◽  
Christopher K. Thompson ◽  
...  

A new method of estimating synaptic drive to multiple, simultaneously recorded motor units provides evidence that the portion of the depolarizing drive from persistent inward currents that contributes to self-sustained firing is similar across motoneurons of different sizes.

2008 ◽  
Vol 100 (1) ◽  
pp. 292-303 ◽  
Author(s):  
Randall K. Powers ◽  
Paul Nardelli ◽  
T. C. Cope

Motoneuron activation is strongly influenced by persistent inward currents (PICs) flowing through voltage-sensitive channels. PIC characteristics and their contribution to the control of motoneuron firing rate have been extensively described in reduced animal preparations, but their contribution to rate modulation in human motoneurons is controversial. It has recently been proposed that the analysis of discharge records of a simultaneously recorded pair of motor units can be used to make quantitative estimates of the PIC contribution, based on the assumption that the firing rate of an early recruited (reporter) unit can be used as a measure of the synaptic drive to a later recruited (test) unit. If the test unit's discharge is augmented by PICs, less synaptic drive will be required to sustain discharge than required to initially recruit it, and the difference in reporter unit discharge (Δ F) at test recruitment and de-recruitment is a measure of the size of the PIC contribution. We applied this analysis to discharge records of pairs of motoneurons in the decerebrate cat preparation, in which motoneuron PICs have been well-characterized and are known to be prominent. Mean Δ F values were positive in 58/63 pairs, and were significantly greater than zero in 40/63 pairs, as would be expected based on PIC characteristics recorded in this preparation. However, several lines of evidence suggest that the Δ F value obtained in a particular motoneuron pair may depend on a number of factors other than the PIC contribution to firing rate.


2015 ◽  
Vol 114 (1) ◽  
pp. 184-198 ◽  
Author(s):  
Randall K. Powers ◽  
C. J. Heckman

Motoneuron activity is strongly influenced by the activation of persistent inward currents (PICs) mediated by voltage-gated sodium and calcium channels. However, the amount of PIC contribution to the activation of human motoneurons can only be estimated indirectly. Simultaneous recordings of pairs of motor units have been used to provide an estimate of the PIC contribution by using the firing rate of the lower threshold unit to provide an estimate of the common synaptic drive to both units, and the difference in firing rate (ΔF) of this lower threshold unit at recruitment and de-recruitment of the higher threshold unit to estimate the PIC contribution to activation of the higher threshold unit. It has recently been suggested that a number of factors other than PIC can contribute to ΔF values, including mechanisms underlying spike frequency adaptation and spike threshold accommodation. In the present study, we used a set of compartmental models representing a sample of 20 motoneurons with a range of thresholds to investigate how several different intrinsic motoneuron properties can potentially contribute to variations in ΔF values. We drove the models with linearly increasing and decreasing noisy conductance commands of different rate of rise and duration and determined the influence of different intrinsic mechanisms on discharge hysteresis (the difference in excitatory drive at recruitment and de-recruitment) and ΔF. Our results indicate that, although other factors can contribute, variations in discharge hysteresis and ΔF values primarily reflect the contribution of dendritic PICs to motoneuron activation.


2020 ◽  
Author(s):  
Lucas B. R Orssatto ◽  
Karen Mackay ◽  
Anthony J Shield ◽  
Raphael L. Sakugawa ◽  
Anthony J. Blazevich ◽  
...  

This study tested the hypothesis that estimates of persistent inward currents (PICs) in the human plantar flexors would increase with the level of voluntary drive. Twenty-one participants volunteered for this study (29.2±2.6 years). High-density surface electromyograms were collected from soleus and gastrocnemius medialis during ramp-shaped isometric contractions to 10%, 20%, and 30% (torque rise of 2%/s and 30-s duration) of each participant's maximal torque. Motor units identified in all the contraction intensities were included in the paired-motor unit analysis to calculate delta frequency (ΔF) and estimate the PICs. Increases in PICs were observed from 10% to 20% (Δ=0.6 pps; p<0.001) and 20% to 30% (Δ=0.5 pps; p<0.001) in soleus, and from 10% to 20% (Δ=1.2 pps; p<0.001) but not 20% to 30% (Δ=0.09 pps; p=0.724) in gastrocnemius medialis. Maximal discharge rate increased for soleus and gastrocnemius medialis from 10% to 20% (respectively, Δ=1.75 pps, p<0.001; and Δ=2.43 pps, p<0.001) and 20% to 30% (respectively, Δ=0.80 pps, p<0.017; and Δ=0.92 pps, p=002). The repeated-measures correlation identified associations between ΔF and increases in maximal discharge rate for both soleus (r=0.64; p<0.001) and gastrocnemius medialis (r=0.77; p<0.001). An increase in voluntary drive tends to increase PIC strength, which has key implications for the control of force but also for comparisons between muscles or between studies when relative force levels might be different. These data indicate that increases in voluntary descending drive amplify PICs in humans and provide an important spinal mechanism for motor unit firing, and thus force output modulation.


2013 ◽  
Vol 110 (12) ◽  
pp. 2863-2872 ◽  
Author(s):  
Jessica M. D'Amico ◽  
Ş. Utku Yavuz ◽  
Ahmet Saraçoğlu ◽  
Elif Sibel Atiş ◽  
Monica A. Gorassini ◽  
...  

In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities such as eating, nonnutritive chewing, clenching, and yawning.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Simon A Sharples ◽  
Gareth B Miles

The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes become staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.


2021 ◽  
Author(s):  
Altamash S Hassan ◽  
Melissa E Fajardo ◽  
Mark Cummings ◽  
Laura Miller McPherson ◽  
Francesco Negro ◽  
...  

Aging is a natural process that causes alterations in the neuromuscular system, which contribute to weakness and reduced quality of life. Reduced firing rates of individual motor units (MUs) likely contribute to weakness, but the mechanisms underlying reduced firing rates are not clear. Persistent inward currents (PICs) are crucial for the initiation, gain control, and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since the concentration of monoamines (i.e. serotonin and norepinephrine) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to young adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps brachii and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (i.e. ΔF) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ~1.6 pulses per second (pps) (P = 0.0292), and ΔF was reduced by ~1.9 pps (P < 0.0001), compared to young adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ~1pps per decade, but there was no relationship in young adults (P = 0.9637). These findings suggest that PICs are reduced in older adults, and, further, age is a significant predictor of estimates of PICs in older adults. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and weakness in older individuals.


2020 ◽  
Vol 124 (2) ◽  
pp. 525-535
Author(s):  
Edward H. Kim ◽  
Jessica M. Wilson ◽  
Christopher K. Thompson ◽  
Charles J. Heckman

With the use of high-density surface array electrodes and convolutive blind source separation algorithm, thousands of motor units were decomposed from the soleus and tibialis anterior muscles. Persistent inward currents were estimated under seated and standing conditions via delta-F (∆F) calculation, and the results showed that unlike the upper limb, the flexor has higher ∆F than the extensor in the lower limb. Future studies will focus on functional significance of the findings.


Author(s):  
Obaid U Khurram ◽  
Francesco Negro ◽  
CJ Heckman ◽  
Christopher K. Thompson

Persistent inward currents (PICs) play an essential role in setting motor neuron gain and shaping motor unit firing patterns. Estimates of PICs in humans can be made using the paired motor unit analysis technique, which quantifies the difference in discharge rate of a lower-threshold motor unit at the recruitment onset and offset of a higher-threshold motor unit (∆F). Because PICs are highly dependent on the level of neuromodulatory drive, ∆F represents an estimate of level of neuromodulation at the level of the spinal cord. Most of the estimates of ∆F are performed under constrained, isometric, seated conditions. In the present study, we used high-density surface EMG arrays to discriminate motor unit firing patterns during isometric seated conditions with torque or EMG visual feedback and during unconstrained standing anterior-to-posterior movements with RMS EMG visual feedback. We were able to apply the paired motor unit analysis technique to the decomposed motor units in each of the three conditions. We hypothesized that ∆F would be higher during unconstrained standing anterior-to-posterior movements compared to the seated conditions, reflecting an increase in the synaptic input to MNs drive while standing. In agreement with previous work, we found that there was no evidence of a difference in ∆F between the seated and standing postures, although slight differences in the initial and peak discharge rates were observed. Taken together, our results suggest that both the standing and seated postures are likely not sufficiently different--both being "upright" postures--to result in large changes in neuromodulatory drive.


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