Voluntary activation of muscle in humans: Does serotonergic neuromodulation matter?

Ionotropic inputs to motoneurones have the capacity to depolarise and hyperpolarise the motoneurone, whereas neuromodulatory inputs control the state of excitability of the motoneurone. Intracellular recordings of motoneurones from in vitro and in situ animal preparations have provided extraordinary insight into the mechanisms that underpin how neuromodulators regulate neuronal excitability. However, far fewer studies have attempted to translate the findings from cellular and molecular studies into a human model. In this review, we focus on the role that serotonin (5-HT) plays in muscle activation in humans. 5-HT is a potent regulator of neuronal firing rates, which can influence the force that can be generated by muscles during voluntary contractions. We firstly outline structural and functional characteristics of the serotonergic system, and then describe how motoneurone discharge can be facilitated and suppressed depending on the 5-HT receptor subtype that is activated. We then provide a narrative on how 5-HT effects can influence voluntary activation during muscle contractions in humans, and detail how 5-HT may be a mediator of exercise-induced fatigue that arises from the central nervous system. (Figure presented.)

A deluxe cosmid vector for transformation of filamentous fungi

The cosmid shuttle vector AN26 for the transformation of some filamentous fungi to hygromycin B resistance was constructed from the plasmid vector AN7-1. The features of the cosmid are: (1) a BamHI cloning site, (2) NotI and SfiI restriction sites surrounding the BamHI site for easy removal of the cloned DNA insert, (3) T3 and SP6 RNA polymerase promoters outside the NotI and SfiI sites for generation of end specific probes, and (4) dual cos sites separated by a unique ClaI site to facilitate cloning of non-size-selected DNA

Short-Interval Cortical Inhibition and Intracortical Facilitation during Submaximal Voluntary Contractions Changes with Fatigue

This study determined whether short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) change during a sustained submaximal isometric contraction. On 2 days, 12 participants (6 men, 6 women) performed brief (7-s) elbow flexor contractions before and after a 10-min fatiguing contraction; all contractions were performed at the level of integrated electromyographic activity (EMG) which produced 25 % maximal unfatigued torque. During the brief 7-s and 10-min submaximal contractions, single (test) and paired (conditioning–test) transcranial magnetic stimuli were applied over the motor cortex (5 s apart) to elicit motor-evoked potentials (MEPs) in biceps brachii. SICI and ICF were elicited on separate days, with a conditioning–test interstimulus interval of 2.5 and 15 ms, respectively. On both days, integrated EMG remained constant while torque fell during the sustained contraction by ~51.5 % from control contractions, perceived effort increased threefold, and MVC declined by 21–22 %. For SICI, the conditioned MEP during control contractions (74.1 ± 2.5 % of unconditioned MEP) increased (less inhibition) during the sustained contraction (last 2.5 min: 86.0 ± 5.1 %; P \u3c 0.05). It remained elevated in recovery contractions at 2 min (82.0 ± 3.8 %; P \u3c 0.05) and returned toward control at 7-min recovery (76.3 ± 3.2 %). ICF during control contractions (conditioned MEP 129.7 ± 4.8 % of unconditioned MEP) decreased (less facilitation) during the sustained contraction (last 2.5 min: 107.6 ± 6.8 %; P \u3c 0.05) and recovered to 122.8 ± 4.3 % during contractions after 2 min of recovery. Both intracortical inhibitory and facilitatory circuits become less excitable with fatigue when assessed during voluntary activity, but their different time courses of recovery suggest different mechanisms for the fatigue-related changes of SICI and ICF

Elbow angle modulates corticospinal excitability to the resting biceps brachii at both spinal and supraspinal levels

NEW FINDINGS: What is the central question of this study? Corticospinal excitability to biceps brachii is known to modulate according to upper-limb posture. Here, cervicomedullary stimulation was used to investigate potential spinal contributions to elbow angle-dependent changes in corticospinal excitability at rest. What is the main finding and its importance? At more extended elbow angles, biceps responses to cervicomedullary stimulation were decreased, whereas cortically evoked responses (normalized to cervicomedullary-evoked responses) were increased. Results suggest decreased spinal excitability but increased cortical excitability as the elbow is placed in a more extended position, an effect that is unlikely to be attributable to cutaneous stretch receptor activation. ABSTRACT: Corticospinal excitability to biceps brachii is known to modulate according to upper-limb posture. In study 1, our aim was to investigate potential spinal contributions to this modulation and the independent effect of elbow angle. Biceps responses to transcranial magnetic stimulation (motor evoked potentials; MEPs) and electrical cervicomedullary stimulation (cervicomedullary motor evoked potentials; CMEPs) were measured at five elbow angles ranging from full extension to 130 deg of flexion. In study 2, possible contributions of cutaneous stretch receptors to elbow angle-dependent excitability changes were investigated by eliciting MEPs and CMEPs in three conditions of skin stretch about the elbow (stretch to mimic full extension, no stretch or stretch to mimic flexion). Each study had 12 participants. Evoked potentials were acquired at rest, with participants seated, the shoulder flexed 90 deg and forearm supinated. The MEPs and CMEPs were normalized to maximal compound muscle action potentials. In study 1, as the elbow was moved to more extended positions, there were no changes in MEPs (P = 0.963), progressive decreases in CMEPs (P \u3c 0.0001; CMEPs at 130 deg flexion ∼220% of full extension) and increases in the MEP/CMEP ratio (P = 0.019; MEP/CMEP at 130 deg flexion ∼20% of full extension). In study 2, there were no changes in MEPs (P = 0.830) or CMEPs (P = 0.209) between skin stretch conditions. Therefore, although results suggest a decrease in spinal and an increase in supraspinal excitability at more extended angles, the mechanism for these changes in corticospinal excitability to biceps is not cutaneous stretch receptor feedback

5-HT2 receptor antagonism reduces human motoneuron output to antidromic activation but not to stimulation of corticospinal axons

The intrinsic electrical properties of motoneurons strongly affect motoneuron excitability to fast-acting excitatory ionotropic inputs. Serotonin (5-HT) is a neurochemical that alters the intrinsic properties of motoneurons, whereby animal models and in vitro experiments indicate that 5-HT increases motoneuron excitability by activating 5-HT2 receptors on the somato-dendritic compartment. In the current study, we examined how antagonism of the 5-HT2 receptor affects motoneuron excitability in humans. We hypothesised that motoneuron excitability would be reduced. The 5-HT2 antagonist cyproheptadine was administered to 10 healthy participants in a double-blinded, placebo-controlled, crossover trial. Electrical cervicomedullary stimulation was used to deliver a synchronised excitatory volley to motoneurons to elicit cervicomedullary motor evoked potentials (CMEPs) in the surface electromyography (EMG) signal of the resting biceps brachii. Likewise, electrical peripheral nerve stimulation was used to generate antidromic spikes in motoneurons and cause recurrent discharges, which were recorded with surface EMG as F-waves in a resting hand muscle. Compared with placebo, we found that 5-HT2 antagonism reduced the amplitude and persistence of F-waves but did not affect CMEP amplitude. 5-HT2 antagonism also reduced maximal contraction strength. The reduced recurrent discharge of motoneurons with 5-HT2 antagonism suggests that 5-HT2 receptors modulate the electrical properties of the initial segment or soma to promote excitability. Conversely, as cyproheptadine did not affect motoneuron excitability to brief synaptic input, but affected maximal contractions requiring sustained input, it seems likely that the 5-HT2-mediated amplification of synaptic input at motoneuron dendrites is functionally significant only when excitatory input activates persistent inward currents

Fatigue-related feedback from calf muscles impairs knee extensor voluntary activation

INTRODUCTION: Fatigue-related group III/IV muscle afferent firing from agonist, antagonist or distal muscles impairs the ability to drive the elbow flexors maximally, that is, reduces voluntary activation. In the lower limb, the effect of feedback from distal muscles on the proximal knee extensors is unknown. Here, we test whether maintained group III/IV afferent feedback from the plantarflexor muscles reduces voluntary activation of the knee extensors. METHODS: On 2 d, voluntary activation of the knee extensors during maximal voluntary contractions (MVCs) was assessed in 12 participants before and after a 3-min fatiguing task of the plantarflexors. On 1 d, an inflatable cuff around the calf occluded blood flow for 2 min immediately postexercise (cuff day). The other day had no occlusion (no-cuff day). Supramaximal stimulation of the femoral nerve elicited superimposed twitches during MVC of the knee extensors and resting twitches 2 to 3 s after relaxation. Pain (0-10 point scale) was reported throughout. RESULTS: In the 2 min after the 3-min fatiguing plantarflexor task, voluntary activation was 5.3% (SD, 7%) lower on the cuff day than on the no-cuff day (P = 0.045), and MVC force was reduced by 13% (SD, 16%) (P = 0.021). The resting twitch was similar on both days (P = 0.98). Pain rated 4.9 points higher with the cuff inflated (P = 0.001). CONCLUSIONS: Maintained group III/IV afferent feedback from the fatigued plantarflexor muscles reduced maximal force and voluntary activation of the unfatigued knee extensors, suggesting that afferents from the calf act centrally to inhibit the ability to drive the motoneurones of the knee extensors

Involuntary sustained firing of plantar flexor motor neurones: effect of electrical stimulation parameters during tendon vibration

Purpose Simultaneous application of tendon vibration and neuromuscular electrical stimulation (NMES) induces an involuntary sustained torque. We examined the effect of different NMES parameters (intensity, pattern of stimulation and pulse width) on the magnitude of the evoked involuntary torque. Methods Plantar flexor torque was recorded during 33-s Achilles tendon vibration with simultaneous 20-Hz NMES bouts on triceps surae (n = 20; 13 women). Intensity was set to elicit 10, 20 or 30% of maximal voluntary contraction torque (MVC), pulse width was narrow (0.2 ms) or wide (1 ms), and the stimulus pattern varied (5 × 2-s or 10 × 1-s). Up to 12 different trials were performed in a randomized order, and then repeated in those who produced a sustained involuntary torque after the cessation of vibration. Results Six of 7 men and 5 of 13 women produced a post-vibration sustained torque. Eight of 20 participants did not complete the 30% trials, as they were perceived as painful. Torque during vibration at the end of NMES and the increase in torque throughout the trial were significantly higher in 20 than 10% trials (n = 11; 9.7 ± 9.0 vs 7.1 ± 6.1% MVC and 4.3 ± 4.5 vs 3.6 ± 3.5% MVC, respectively). Post-vibration sustained torque was higher in wide pulse-width trials (5.4 ± 5.9 vs 4.1 ± 4.3% MVC). Measures of involuntary torque were not different between 20 and 30% trials (n = 8). Conclusion Bouts of 5 × 2-s NMES with wide pulse width eliciting 20% MVC provides the most robust responses and could be used to maximise the production of involuntary torque in triceps surae

Prevalence of motor impairment in residents of New South Wales, Australia aged 55 years and over: Cross-sectional survey of the 45 and Up cohort

BACKGROUND: The population prevalence of many diseases is known. However, little is known of the population prevalence of motor impairments. METHODS: The aim of this study was to determine the point prevalence of specific motor impairments (weakness, fatigue, contracture, impaired balance and impaired coordination) in the population aged 55 years and older resident in New South Wales, Australia in 2018. 55,210 members of the 45 and Up cohort were invited to participate in a follow-up survey that included questions on motor impairment. Responses were received from 20,141 people (36%). Calibrated estimates of prevalence of specific motor impairments, and of having at least one motor impairment, were obtained using survey weights based on the known multivariate distributions of age, gender and geographical location (28 regions) in the population. RESULTS: More than one-third of adults aged over 55 residing in New South Wales have difficulty using their hands, arms or legs. The prevalence of each motor impairment (muscle weakness, fatigue, contracture, impaired balance or impaired coordination) in this population is between 4 and 12%. The prevalence of at least one of these impairments is 21%. The prevalence of at least one impairment in people aged 85 and over is 42%. Women consistently had more difficulty using hands, arms and legs, and more motor impairment, than men. Difficulty using hands, arms and legs and the prevalence of all motor impairments, especially poor balance, greatly increased with age. CONCLUSION: The prevalence of specific motor impairments in older Australian adults is high - comparable to that of the most prevalent diseases. There may be merit in considering motor impairment as a significant public health problem in its own right

Fortification and health: challenges and opportunities.

Fortification is the process of adding nutrients or non-nutrient bioactive components to edible products (e.g., food, food constituents, or supplements). Fortification can be used to correct or prevent widespread nutrient intake shortfalls and associated deficiencies, to balance the total nutrient profile of a diet, to restore nutrients lost in processing, or to appeal to consumers looking to supplement their diet. Food fortification could be considered as a public health strategy to enhance nutrient intakes of a population. Over the past century, fortification has been effective at reducing the risk of nutrient deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the world today is very different from when fortification emerged in the 1920s. Although early fortification programs were designed to eliminate deficiency diseases, current fortification programs are based on low dietary intakes rather than a diagnosable condition. Moving forward, we must be diligent in our approach to achieving effective and responsible fortification practices and policies, including responsible marketing of fortified products. Fortification must be applied prudently, its effects monitored diligently, and the public informed effectively about its benefits through consumer education efforts. Clear lines of authority for establishing fortification guidelines should be developed and should take into account changing population demographics, changes in the food supply, and advances in technology. This article is a summary of a symposium presented at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 on current issues involving fortification focusing primarily on the United States and Canada and recommendations for the development of responsible fortification practices to ensure their safety and effectiveness