Structure and Function of the Mammalian Neuromuscular Junction.

The mammalian neuromuscular junction (NMJ) comprises a presynaptic terminal, a postsynaptic receptor region on the muscle fiber (endplate), and the perisynaptic (terminal) Schwann cell. As with any synapse, the purpose of the NMJ is to transmit signals from the nervous system to muscle fibers. This neural control of muscle fibers is organized as motor units, which display distinct structural and functional phenotypes including differences in pre- and postsynaptic elements of NMJs. Motor units vary considerably in the frequency of their activation (both motor neuron discharge rate and duration/duty cycle), force generation, and susceptibility to fatigue. For earlier and more frequently recruited motor units, the structure and function of the activated NMJs must have high fidelity to ensure consistent activation and continued contractile response to sustain vital motor behaviors (e.g., breathing and postural balance). Similarly, for higher force less frequent behaviors (e.g., coughing and jumping), the structure and function of recruited NMJs must ensure short-term reliable activation but not activation sustained for a prolonged period in which fatigue may occur. The NMJ is highly plastic, changing structurally and functionally throughout the life span from embryonic development to old age. The NMJ also changes under pathological conditions including acute and chronic disease. Such neuroplasticity often varies across motor unit types. © 2022 American Physiological Society. Compr Physiol 12:1-36, 2022.

Mitochondrial adaptations to inactivity in diaphragm muscle fibers.

Type I and IIa diaphragm muscle (DIAm) fibers comprise slow and fast fatigue-resistant motor units that are recruited to accomplish breathing and thus have a high duty cycle. In contrast, type IIx/IIb fibers comprise more fatigable fast motor units that are infrequently recruited for airway protective and straining behaviors. We hypothesize that mitochondrial structure and function in type I and IIa DIAm fibers adapt in response to inactivity imposed by spinal cord hemisection at C2 (C2SH). At 14 days after C2SH, the effect of inactivity on mitochondrial structure and function was assessed in DIAm fibers. Mitochondria in DIAm fibers were labeled using MitoTracker Green (Thermo Fisher Scientific), imaged in three-dimensions (3-D) by fluorescence confocal microscopy, and images were analyzed for mitochondrial volume density (MVD) and complexity. DIAm homogenate from either side was assessed for PGC1α, Parkin, MFN2, and DRP1 using Western blot. In alternate serial sections of the same DIAm fibers, the maximum velocity of the succinate dehydrogenase reaction (SDHmax) was determined using a quantitative histochemical technique. In all groups and both sides of the DIAm, type I and IIa DIAm fibers exhibited higher MVD, with more filamentous mitochondria and had higher SDHmax normalized to both fiber volume and mitochondrial volume compared with type IIx/IIb Diam fibers. In the inactive right side of the DIAm, mitochondria became fragmented and MVD decreased in all fiber types compared with the intact side and sham controls, consistent with the observed reduction in PGC1α and increased Parkin and DRP1 expression. In the inactive side of the DIAm, the reduction in SDHmax was found only for type I and IIa fibers. These results show that there are intrinsic fiber-type-dependent differences in the structure and function of mitochondria in DIAm fibers. Following C2SH-induced inactivity, mitochondrial structure (MVD and fragmentation) and function (SDHmax) were altered, indicating that inactivity influences all DIAm fiber types, but inactivity disproportionately affected SDHmax in the more intrinsically active type I and IIa fibers.NEW & NOTEWORTHY Two weeks of diaphragm (DIAm) inactivity imposed by C2SH caused reduced mitochondrial volume density, mitochondrial fragmentation, and a concomitant reduction of SDHmax in type I and IIa DIAm fibers on the lesioned side. Type I and IIa DIAm fibers were far more sensitive to inactivation than type IIx/IIb fibers, which exhibited little pathology. Our results indicate that mitochondria in DIAm fibers are plastic in response to varying levels of activity.

Mitochondrial Fragmentation and Dysfunction in Type IIx/IIb Diaphragm Muscle Fibers in 24-Month Old Fischer 344 Rats.

Sarcopenia is characterized by muscle fiber atrophy and weakness, which may be associated with mitochondrial fragmentation and dysfunction. Mitochondrial remodeling and biogenesis in muscle fibers occurs in response to exercise and increased muscle activity. However, the adaptability mitochondria may decrease with age. The diaphragm muscle (DIAm) sustains breathing, via recruitment of fatigue-resistant type I and IIa fibers. More fatigable, type IIx/IIb DIAm fibers are infrequently recruited during airway protective and expulsive behaviors. DIAm sarcopenia is restricted to the atrophy of type IIx/IIb fibers, which impairs higher force airway protective and expulsive behaviors. The aerobic capacity to generate ATP within muscle fibers depends on the volume and intrinsic respiratory capacity of mitochondria. In the present study, mitochondria in type-identified DIAm fibers were labeled using MitoTracker Green and imaged in 3-D using confocal microscopy. Mitochondrial volume density was higher in type I and IIa DIAm fibers compared with type IIx/IIb fibers. Mitochondrial volume density did not change with age in type I and IIa fibers but was reduced in type IIx/IIb fibers in 24-month rats. Furthermore, mitochondria were more fragmented in type IIx/IIb compared with type I and IIa fibers, and worsened in 24-month rats. The maximum respiratory capacity of mitochondria in DIAm fibers was determined using a quantitative histochemical technique to measure the maximum velocity of the succinate dehydrogenase reaction (SDH max ). SDH max per fiber volume was higher in type I and IIa DIAm fibers and did not change with age. In contrast, SDH max per fiber volume decreased with age in type IIx/IIb DIAm fibers. There were two distinct clusters for SDH max per fiber volume and mitochondrial volume density, one comprising type I and IIa fibers and the second comprising type IIx/IIb fibers. The separation of these clusters increased with aging. There was also a clear relation between SDH max per mitochondrial volume and the extent of mitochondrial fragmentation. The results show that DIAm sarcopenia is restricted to type IIx/IIb DIAm fibers and related to reduced mitochondrial volume, mitochondrial fragmentation and reduced SDH max per fiber volume.

Exercise with TENS does not augment gains in balance and strength for dancers.

Electrical stimulation modulates sensory feedback and improves motor performance, at least for individuals with compromised sensorimotor function. The purpose of this study was to determine the effectiveness of a 4-wk intervention with transcutaneous electrical nerve stimulation (TENS) at improving strength and balance in dancers. Nineteen dancers completed a timed, single-leg balance test, the Y-balance test, and contractions with the hip flexor and knee extensor muscles to assess maximal strength and force steadiness. They completed 4-wks of moderate-intensity bodyweight exercises (3x/wk) and were pseudo-randomized to either a Treatment or Sham group in a single-blind design. The Treatment group received constant TENS over the hamstring muscles during the exercises, whereas the Sham group was exposed to a brief TENS current. The data were pooled due to few significant between-group differences from before to after the intervention. Most outcome measures significantly improved: hip extensor muscles were stronger (P ≤ 0.01), time stood on a single-leg with eyes closed increased (P = 0.02), and the distance reached during the Y-balance test increased (P ≤ 0.001). The improvement in scores on the Y-balance test exceeded the minimal clinically significant change. Twelve sessions of moderate-intensity bodyweight exercises improved muscle strength and balance in experienced dancers. The addition of TENS, however, did not augment the gains in function.

Force control during submaximal isometric contractions is associated with walking performance in persons with multiple sclerosis.

Individuals with multiple sclerosis (MS) experience progressive declines in movement capabilities, especially walking performance. The purpose of our study was to compare the amount of variance in walking performance that could be explained by the functional capabilities of lower leg muscles in persons with MS and a sex- and age-matched control group. Participants performed two walking tests (6-min walk and 25-ft walk), strength tests for the plantar flexor and dorsiflexor muscles, and steady submaximal (10% and 20% maximum) isometric contractions. High-density electromyography (EMG) was recorded during the steady contractions, and the signals were decomposed to identify the discharge times of concurrently active motor units. There were significant differences between the two groups in the force fluctuations during the steady contractions (force steadiness), the strength of the plantar flexor and dorsiflexor muscles, and the discharge characteristics during the steady contractions. Performance on the two walking tests by the MS group was moderately associated with force steadiness of the plantar flexor and dorsiflexor muscles; worse force steadiness was associated with poorer walking performance. In contrast, the performance of the control group was associated with muscle strength (25-ft test) and force steadiness of the dorsiflexors and variance in common input of motor units to the plantar flexors (6-min test). These findings indicate that a reduction in the ability to maintain a steady force during submaximal isometric contractions is moderately associated with walking performance of persons with MS.NEW & NOTEWORTHY The variance in walking endurance and walking speed was associated with force control of the lower leg muscles during submaximal isometric contractions in individuals with multiple sclerosis (MS). In contrast, the fast walking speed of a sex- and age-matched control group was associated with the strength of lower leg muscles. These findings indicate that moderate declines in the walking performance of persons with MS are more associated with impairments in force control rather than decreases in muscle strength.

Differences in postural sway among healthy adults are associated with the ability to perform steady contractions with leg muscles.

Upright standing involves small displacements of the center of mass about the base of support. These displacements are often quantified by measuring various kinematic features of the center-of-pressure trajectory. The plantar flexors have often been identified as the key muscles for the control of these displacements; however, studies have suggested that the hip abductor and adductors may also be important. The purpose of our study was to determine the association between the force capabilities of selected leg muscles and sway-area rate across four balance conditions in young (25 ± 4 years; 12/19 women) and older adults (71 ± 5 years; 5/19 women). Due to the marked overlap in sway-area rate between the two age groups, the data were collapsed, and individuals were assigned to groups of low- and high-sway area rates based on a k-medoid cluster analysis. The number of participants assigned to each group varied across balance conditions and a subset of older adults was always included in the low-sway group for each balance condition. The most consistent explanatory variable for the variance in sway-area rate was force control of the hip abductors and ankle dorsiflexors as indicated by the magnitude of the normalized force fluctuations (force steadiness) during a submaximal isometric contraction. The explanatory power of the regression models varied across conditions, thereby identifying specific balance conditions that should be examined further in future studies of postural control.

Electrical nerve stimulation modulates motor unit activity in contralateral biceps brachii during steady isometric contractions.

The purpose of our study was to compare the influence of five types of electrical nerve stimulation delivered through electrodes placed over the right biceps brachii on motor unit activity in the left biceps brachii during an ongoing steady isometric contraction. The electrical stimulation protocols comprised different combinations of pulse duration (0.2 and 1.0 ms), stimulus frequency (50 and 90 Hz), and stimulus current (greater or less than motor threshold). The electrical nerve stimulation protocols were applied over the muscle of the right elbow flexors of 13 participants (26 ± 3 yr) while they performed voluntary contractions with the left elbow flexors to match a target force set at 10% of maximum. All five types of electrical nerve stimulation increased the absolute amplitude of the electromyographic (EMG) signal recorded from the left biceps brachii with high-density electrodes. Moreover, one stimulation condition (1 ms, 90 Hz) had a consistent influence on the centroid location of the EMG amplitude distribution and the average force exerted by the left elbow flexors. Another stimulation condition (0.2 ms, 90 Hz) reduced the coefficient of variation for force during the voluntary contraction, and both low-frequency conditions (50 Hz) increased the duration of the mean interspike interval of motor unit action potentials after the stimulation had ended. The findings indicate that the contralateral effects of electrical nerve stimulation on the motor neuron pool innervating the homologous muscle can be influenced by both stimulus pulse duration and stimulus frequency. NEW & NOTEWORTHY Different types of electrical nerve stimulation delivered through electrodes placed over the right biceps brachii modulated the ongoing motor unit activity in the left biceps brachii. Although the effects varied with stimulus pulse duration, frequency, and current, all five types of electrical nerve stimulation increased the amplitude of the electromyographic activity in the left biceps brachii. Moreover, most of the effects in the left arm occurred after the electrical nerve stimulation of the right arm had been terminated.

The impact of sexual arousal on sexual risk-taking: a qualitative study.

Quantitative studies have shown that both straight and gay men with a low propensity for inhibition of sexual arousal are more likely to engage in unprotected sex in the face of risk. This article reports findings from an interview study of both straight and gay men focusing on the individual's experience of the impact of sexual arousal on risk management. The impact of the immediate post-ejaculatory period and the effects of condoms on sexual arousal are also considered. Three patterns were apparent in both groups: (a) low inhibition of sexual arousal associated with impaired risk management; (b) low inhibition of arousal in risk situations leading to establishment of planning ahead, and (c) no impact of sexual arousal on risk management. We also consider the contrast between committed and uncommitted relationships. Lastly, we consider possible mediating mechanisms between sexual arousal and risk management and discuss the implications of these varied patterns for interventions to reduce high-risk sexual behavior.