Ageing reduces persistent inward current contribution to motor neurone firing: Potential mechanisms and the role of exercise

Nervous system deterioration is a primary driver of age-related motor impairment. The motor neurones, which act as the interface between the central nervous system and the muscles, play a crucial role in amplifying excitatory synaptic input to produce the desired motor neuronal firing output. For this, they utilise their ability to generate persistent (long-lasting) depolarising currents that increase cell excitability, and both amplify and prolong the output activity of motor neurones for a given synaptic input. Modulation of these persistent inward currents (PICs) contributes to the motor neurones’ capacities to attain the required firing frequencies and rapidly modulate them to competently complete most tasks. Thus, PICs are crucial for adequate movement generation. Impairments in intrinsic motor neurone properties can impact motor unit firing capacity, with convincing evidence indicating that the PIC contribution to motor neurone firing is reduced in older adults. Indeed, this could be an important mechanism underpinning the age-related reductions in strength and physical function. Furthermore, resistance training has emerged as a promising intervention to counteract age-associated PIC impairments, with changes in PICs being correlated with improvements in muscular strength and physical function after training. In this review, we present the current knowledge of the PIC magnitude decline during ageing and discuss whether reduced serotonergic and noradrenergic input onto the motor neurones, voltage-gated calcium channel dysfunction or inhibitory input impairments are candidates that: (i) explain age-related reductions in the PIC contribution to motor neurone firing and (ii) underpin the enhanced PIC contribution to motor neurone firing following resistance training in older adults. (Figure presented.)

Facilitation–inhibition control of motor neuronal persistent inward currents in young and older adults

A well-coordinated facilitation–inhibition control of motor neuronal persistent inward currents (PICs) via diffuse neuromodulation and local inhibition is essential to ensure motor units discharge at required times and frequencies. Present best estimates indicate that PICs are reduced in older adults; however, it is not yet known whether PIC facilitation–inhibition control is also altered with ageing. We investigated the responses of PICs to (i) a remote handgrip contraction, which is believed to diffusely increase serotonergic input onto motor neurones, and (ii) tendon vibration of the antagonist muscle, which elicits reciprocal inhibition, in young and older adults. High-density surface electromyograms were collected from soleus and tibialis anterior of 18 young and 26 older adults during triangular-shaped plantar and dorsiflexion contractions to 20 % (handgrip experiments) and 30 % (vibration experiments) of maximum torque (rise-decline rate of 2 % / s). A paired-motor-unit analysis was used to calculate ∆F, which is assumed to be proportional to PIC strength. ΔF increased in both soleus (0.55 peaks per second (pps), 16.0 %) and tibialis anterior (0.42 pps, 11.4 %) after the handgrip contraction independent of age. Although antagonist tendon vibration reduced ΔF in soleus (0.28 pps, 12.6 %) independent of age, less reduction was observed in older (0.42 pps, 10.7 %) than young adults (0.72 pps, 17.8 %) in tibialis anterior. Our data indicate a preserved ability of older adults to amplify PICs following a remote handgrip contraction, during which increased serotonergic input onto the motor neurones is expected, in both lower leg muscles. However, PIC deactivation in response to reciprocal inhibition was impaired with ageing in tibialis anterior despite being preserved in soleus. (Figure presented.). Key points: Motor neuronal persistent inward currents (PICs) are facilitated via diffuse neuromodulation and deactivated by local inhibition to ensure motor units discharge at required times and frequencies, allowing normal motor behaviour. PIC amplitudes appear to be reduced with ageing; however, it is not known whether PIC facilitation–inhibition control is also altered. Remote handgrip contraction, which should diffusely increase serotonergic input onto motor neurones, facilitated PICs similarly in both soleus and tibialis anterior of young and older adults. Antagonist tendon vibration, which induces reciprocal inhibition, reduced PICs in soleus in both young and older adults but had less effect in tibialis anterior in older adults. Data from lower-threshold motor units during low-force contractions suggest that PIC facilitation is preserved with ageing in soleus and tibialis anterior. However, the effect of reciprocal inhibition on the contribution of PICs to motor neurone discharge seems reduced in tibialis anterior but preserved in soleus

Facilitation-inhibition control of motor neuronal persistent inward currents in young and older adults

Abstract: A well-coordinated facilitation–inhibition control of motor neuronal persistent inward currents (PICs) via diffuse neuromodulation and local inhibition is essential to ensure motor units discharge at required times and frequencies. Present best estimates indicate that PICs are reduced in older adults; however, it is not yet known whether PIC facilitation–inhibition control is also altered with ageing. We investigated the responses of PICs to (i) a remote handgrip contraction, which is believed to diffusely increase serotonergic input onto motor neurones, and (ii) tendon vibration of the antagonist muscle, which elicits reciprocal inhibition, in young and older adults. High-density surface electromyograms were collected from soleus and tibialis anterior of 18 young and 26 older adults during triangular-shaped plantar and dorsiflexion contractions to 20% (handgrip experiments) and 30% (vibration experiments) of maximum torque (rise-decline rate of 2%/s). A paired-motor-unit analysis was used to calculate ∆F, which is assumed to be proportional to PIC strength. ΔF increased in both soleus (0.55 peaks per second (pps), 16.0%) and tibialis anterior (0.42 pps, 11.4%) after the handgrip contraction independent of age. Although antagonist tendon vibration reduced ΔF in soleus (0.28 pps, 12.6%) independent of age, less reduction was observed in older (0.42 pps, 10.7%) than young adults (0.72 pps, 17.8%) in tibialis anterior. Our data indicate a preserved ability of older adults to amplify PICs following a remote handgrip contraction, during which increased serotonergic input onto the motor neurones is expected, in both lower leg muscles. However, PIC deactivation in response to reciprocal inhibition was impaired with ageing in tibialis anterior despite being preserved in soleus. (Figure presented.). Key points: Motor neuronal persistent inward currents (PICs) are facilitated via diffuse neuromodulation and deactivated by local inhibition to ensure motor units discharge at required times and frequencies, allowing normal motor behaviour. PIC amplitudes appear to be reduced with ageing; however, it is not known whether PIC facilitation–inhibition control is also altered. Remote handgrip contraction, which should diffusely increase serotonergic input onto motor neurones, facilitated PICs similarly in both soleus and tibialis anterior of young and older adults. Antagonist tendon vibration, which induces reciprocal inhibition, reduced PICs in soleus in both young and older adults but had less effect in tibialis anterior in older adults. Data from lower-threshold motor units during low-force contractions suggest that PIC facilitation is preserved with ageing in soleus and tibialis anterior. However, the effect of reciprocal inhibition on the contribution of PICs to motor neurone discharge seems reduced in tibialis anterior but preserved in soleus.</p

Neuromuscular determinants of explosive torque: Differences among strength‐trained and untrained young and older men

This study compared the differences in neural and muscular mechanisms related to explosive torque in chronically strength-trained young and older men (>5 years). Fifty-four participants were allocated into four groups according to age and strength training level: older untrained (n = 14; 65.6 ± 2.9 years), older trained (n = 12; 63.6 ± 3.8 years), young untrained (n = 14; 26.2 ± 3.7 years), and young trained (n = 14; 26.7 ± 3.4 years). Knee extension isometric voluntary explosive torque (absolute and normalized as a percentage of maximal voluntary torque) was assessed at the beginning of the contraction (ie, 50, 100, and 150 ms—T50, T100, and T150, respectively), and surface electromyogram (sEMG) amplitude (normalized as a percentage of sEMG recorded during maximal voluntary isometric contraction) at 0-50, 50-100, and 100-150 time windows. Supramaximal electrically evoked T50 was assessed with octet trains delivered to the femoral nerve (8 pulses at 300 Hz). Voluntary T50, T100, and T150 were higher for trained than untrained in absolute (P  0.417). Chronically strength-trained young and older men presented a greater explosive torque than their untrained pairs. In young trained, the greater explosive performance was attributed to enhanced muscular and neural mechanisms, while in older trained to neural mechanisms only.</p

Intrinsic motoneuron excitability is reduced in soleus and tibialis anterior of older adults

Age-related deterioration within both motoneuron and monoaminergic systems should theoretically reduce neuromodulation by weakening motoneuronal persistent inward current (PIC) amplitude. 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 ± 4 years) and 17 young adults (29 ± 5 years) to investigate motor unit discharge behaviors. 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), which has been used to differentiate between the effects of synaptic excitation and intrinsic motoneuronal properties and is assumed to be proportional to PIC amplitude. Soleus and tibialis anterior motor units in older adults had lower ΔFs calculated with either the pairwise [-0.99 and -1.46 pps; -35.4 and -33.5%, respectively] or composite (-1.18 and -2.28 pps; -32.1 and -45.2%, respectively) methods. Their motor units also had lower peak discharge rates (-2.14 and -2.03 pps; -19.7 and -13.9%, respectively) and recruitment thresholds (-1.50 and -2.06% of maximum, respectively) than young adults. These results demonstrate reduced intrinsic motoneuron excitability during low-force contractions in older adults, likely mediated by decreases in the amplitude of persistent inward currents. Our findings might be explained by deterioration in the motoneuron or monoaminergic systems and could contribute to the decline in motor function during aging; these assumptions should be explicitly tested in future investigations