Estimates of persistent inward currents in lower limb motoneurons are larger in females than in males

Abstract

Non-invasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of participants in human and non-human animal physiology studies are male, and it is assumed mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed effects models to determine if peak discharge rate and estimates of PICs were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of sex-differences in peak discharge rates across all muscles, estimates of PICs were larger (χ2(1) = 6.26, p = 0.012) in females (4.73 ± 0.242 pps) than males (3.81 ± 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns.

Effects of jaw clenching and mental stress on persistent inward currents estimated by two different methods

“…Moreover, it remains unclear whether there are sex differences in PICs. The absence of differences in GM ΔF between males and females reported in our current and previous studies (Mesquita et al, 2022) contrasts with recent evidence of greater ΔF in lower limb muscles of females (Jenz et al, 2023). However, current observations are based on small sample sizes (up to 9 vs. 9 in our observations and 10 vs. 10 in Jenz et al, 2023) and future studies could usefully include a greater number of females and males.…”

“…The absence of differences in GM ΔF between males and females reported in our current and previous studies (Mesquita et al, 2022) contrasts with recent evidence of greater ΔF in lower limb muscles of females (Jenz et al, 2023). However, current observations are based on small sample sizes (up to 9 vs. 9 in our observations and 10 vs. 10 in Jenz et al, 2023) and future studies could usefully include a greater number of females and males. Another important factor to consider in the future is the possible effect of sex hormone variation during the menstrual cycle on synaptic inhibition (Haage et al, 2002), neuromodulation (Bethea et al, 2002;Koldzic-Zivanovic et al, 2004;Smith et al, 2004) and, thus, PIC activity.…”

Menstrual Cycle Associated Alteration of Vastus Lateralis Motor Unit Function

“…When comparing across the cycle, MUP area was greatest in the mid luteal phase at both contraction levels. We have previously reported that at a given contraction level, females have smaller MUPs than males but possibly compensate for this with higher comparative firing rates [ 51 ], likely mediated by larger PIC estimates [ 73 ]. The same may be true here, where MUP area is greater when firing rate is lowest, indicating a minor alteration of recruitment strategy during the mid-luteal phase, compensating for reductions in firing rate at the same relative contraction intensity.…”

Excitatory drive to spinal motoneurones is necessary for serotonin to modulate motoneurone excitability via 5‐HT2 receptors in humans

“…Thus, evoked responses from motor cortical and cervicomedullary stimulation are possibly less affected than the volitional activity of spinal motoneurones by dendritic PICs. Another consideration for this study is that fluctuations in estradiol and progesterone associated with the menstrual cycle could influence serotonergic modulation of motor activity (Bethea et al, 1998; Jenz et al, 2023; Sherman & Korenman, 1975). However, as only two females were included in our analysis we contend that the effects of sex had minimal effects on the results.…”