Estimates of persistent inward currents are reduced in upper limb motor units of older adults

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.

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Differences in estimated persistent inward currents between ankle flexors and extensors in humans

Journal of Neurophysiology ◽

10.1152/jn.00746.2019 ◽

2020 ◽

Vol 124 (2) ◽

pp. 525-535

Author(s):

Edward H. Kim ◽

Jessica M. Wilson ◽

Christopher K. Thompson ◽

Charles J. Heckman

Keyword(s):

Upper Limb ◽

Lower Limb ◽

Tibialis Anterior ◽

Motor Units ◽

Separation Algorithm ◽

Persistent Inward Currents ◽

Future Studies ◽

Inward Currents ◽

Density Surface ◽

Convolutive Blind Source Separation

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.

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Estimation of the Contribution of Intrinsic Currents to Motoneuron Firing Based on Paired Motoneuron Discharge Records in the Decerebrate Cat

Journal of Neurophysiology ◽

10.1152/jn.90296.2008 ◽

2008 ◽

Vol 100 (1) ◽

pp. 292-303 ◽

Cited By ~ 30

Author(s):

Randall K. Powers ◽

Paul Nardelli ◽

T. C. Cope

Keyword(s):

Firing Rate ◽

Motor Units ◽

Unit Discharge ◽

Decerebrate Cat ◽

Persistent Inward Currents ◽

Quantitative Estimates ◽

Number Of Factors ◽

Inward Currents ◽

The Difference ◽

Synaptic Drive

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.

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Persistent Inward Currents Increase With The Level Of Voluntary Drive In Plantar Flexor Low-Threshold Motor Units

10.1101/2020.12.11.420570 ◽

2020 ◽

Author(s):

Lucas B. R Orssatto ◽

Karen Mackay ◽

Anthony J Shield ◽

Raphael L. Sakugawa ◽

Anthony J. Blazevich ◽

...

Keyword(s):

Motor Unit ◽

Repeated Measures ◽

Discharge Rate ◽

Motor Units ◽

Plantar Flexors ◽

Force Output ◽

Persistent Inward Currents ◽

Gastrocnemius Medialis ◽

Inward Currents ◽

Maximal Discharge

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.

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Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

eLife ◽

10.7554/elife.71385 ◽

2021 ◽

Vol 10 ◽

Author(s):

Simon A Sharples ◽

Gareth B Miles

Keyword(s):

Postnatal Development ◽

Motor Units ◽

Intrinsic Properties ◽

Size Principle ◽

Differential Activation ◽

Persistent Inward Currents ◽

Poor Predictor ◽

Whole Cell Patch Clamp ◽

Inward Currents ◽

Patch Clamp Electrophysiology

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.

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INTRINSIC MOTOR NEURONE EXCITABILITY IS REDUCED IN SOLEUS AND TIBIALIS ANTERIOR OF OLDER ADULTS

10.1101/2021.06.23.449552 ◽

2021 ◽

Author(s):

Lucas B R Orssatto ◽

David N Borg ◽

Anthony J Blazevich ◽

Raphael L Sakugawa ◽

Anthony J Shield ◽

...

Keyword(s):

Older Adults ◽

Young Adults ◽

Motor Unit ◽

Tibialis Anterior ◽

Motor Units ◽

Motor Neurone ◽

Age Related ◽

Inward Currents ◽

Motor Neurones ◽

Intrinsic Motor

Age-related deterioration within both motor neurones and monoaminergic systems should theoretically reduce neuromodulation by weakening motor neuronal persistent inward current (PIC) strength. However, this assumption remains untested. Surface electromyographic signals were collected using two 32-channel electrode matrices placed on soleus and tibialis anterior of 25 older adults (70±4years) and 17 young adults (29±5 years) to investigate motor unit discharge behaviours. Participants performed triangular-shaped plantar and dorsiflexion contractions to 20% of maximum torque at a rise-decline rate of 2%/s of each participant's maximal torque. Pairwise and composite paired-motor unit analyses were adopted to calculate delta frequency (ΔF) and estimate PIC amplitudes. ΔF has been used to differentiate between the effects of synaptic excitation and intrinsic motor neuronal properties and is assumed to be proportional to PIC amplitude. The results show that soleus and tibialis anterior motor units in older adults had lower ΔFs when calculated with the pairwise (-0.99 and -1.29 pps, respectively) or composite (-1.65 and -2.26 pps, respectively) methods. Older adults' motor units discharged at lower rates (-2.14 and -2.03 pps, respectively) and were recruited at lower torque levels (-1.50 and -2.06% of maximum, respectively) than young adults. These results demonstrate reduced intrinsic motor neurone excitability during low-force contractions in older adults, likely mediated by decreases in the strength of persistent inward currents. Our findings might be explained by deterioration in the motor neurones or monoaminergic systems, and could contribute to the decline in motor function during ageing; these assumptions should be explicitly tested in future investigations.

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

Journal of Neurophysiology ◽

10.1152/jn.00194.2020 ◽

2020 ◽

Vol 124 (1) ◽

pp. 63-85 ◽

Cited By ~ 3

Author(s):

Babak Afsharipour ◽

Nagib Manzur ◽

Jennifer Duchcherer ◽

Keith F. Fenrich ◽

Christopher K. Thompson ◽

...

Keyword(s):

Firing Rate ◽

Motor Units ◽

New Method ◽

Persistent Inward Currents ◽

Sustained Activity ◽

Inward Currents ◽

Synaptic Drive

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.

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Inhibition linearizes firing rate responses in human motor units: implications for the role of persistent inward currents

The Journal of Physiology ◽

10.1113/jp272823 ◽

2016 ◽

Vol 595 (1) ◽

pp. 179-191 ◽

Cited By ~ 15

Author(s):

Ann L. Revill ◽

Andrew J. Fuglevand

Keyword(s):

Firing Rate ◽

Motor Units ◽

Persistent Inward Currents ◽

Inward Currents ◽

Human Motor ◽

Human Motor Units

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Estimates of persistent inward currents in tibialis anterior motor units during standing ramped contraction tasks in humans

Journal of Neurophysiology ◽

10.1152/jn.00144.2021 ◽

2021 ◽

Author(s):

Obaid U Khurram ◽

Francesco Negro ◽

CJ Heckman ◽

Christopher K. Thompson

Keyword(s):

Motor Unit ◽

Visual Feedback ◽

Discharge Rate ◽

Motor Units ◽

Firing Patterns ◽

Persistent Inward Currents ◽

Analysis Technique ◽

Motor Unit Firing ◽

Inward Currents ◽

Unit Analysis

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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Motor Unit Rotation in a Variety of Human Muscles

Journal of Neurophysiology ◽

10.1152/jn.00278.2009 ◽

2009 ◽

Vol 102 (4) ◽

pp. 2265-2272 ◽

Cited By ~ 31

Author(s):

Parveen Bawa ◽

Chantelle Murnaghan

Keyword(s):

Motor Unit ◽

Motor Units ◽

Motor Command ◽

Emg Activity ◽

Persistent Inward Currents ◽

Small Hand ◽

Abductor Digiti Minimi ◽

Inward Currents ◽

Low Threshold ◽

The Subject

The phenomena of substitution and rotation among motor units of a muscle were examined in seven different muscles. Intramuscular motor unit activity and surface electromyographic (EMG) activity were recorded from one of the following muscles: abductor digiti minimi, first dorsal interosseous, extensor digitorum communis, flexor and extensor carpi radialis, tibialis anterior, and soleus. The subject was asked to discharge a discernible unit at a comfortable constant or rhythmically (pseudosinusoidally) modulated rate with audio and visual feedback. Results are reported from a total of 42 sets of motor units from all seven muscles. We observed that when a subject fired a motor unit for a long period, an additional motor unit frequently started to discharge after a few minutes. When the subject was asked to keep activity down to one unit, very often it was Unit 1 that dropped and Unit 2 continued to fire. Whereas Unit 2 had fired for a few minutes, Unit 1 resumed firing without any conscious effort by the subject. If the subject was then asked to retain just one unit, it was Unit 2 that dropped. Rhythmic modulation of firing rate of a tonically firing unit showed that whereas the threshold of this unit increased, the threshold of a phasically discharging unit decreased substantially. The increase in threshold of a tonically discharging unit is suggested to arise from inactivation of Na+ and Ca2+ channels and the decrease in threshold of higher-threshold units is suggested to arise from an increase in persistent inward currents that may occur during prolonged contractions. Whether a unit stops or starts to fire is suggested to depend on a balance between the strength of the central motor command, persistent inward currents, and inactivation of voltage-gated channels. Such rotations among low-threshold motoneurons would ensure low-level sustained contractions to be viable not only in small hand muscles but also in larger limb muscles.

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