A fundamental challenge for the nervous system is to encode signals spanning many orders of magnitude with neurons of limited bandwidth. To meet this challenge, perceptual systems use gain control. However, whether the motor system uses an analogous mechanism is essentially unknown. Neuromodulators, such as serotonin, are prime candidates for gain control signals during force production. Serotonergic neurons project diffusely to motor pools, and, therefore, force production by one muscle should change the gain of others. Here we present behavioral and pharmaceutical evidence that serotonin modulates the input-output gain of motoneurons in humans. By selectively changing the efficacy of serotonin with drugs, we systematically modulated the amplitude of spinal reflexes. More importantly, force production in different limbs interacts systematically, as predicted by a spinal gain control mechanism. Psychophysics and pharmacology suggest that the motor system adopts gain control mechanisms, and serotonin is a primary driver for their implementation in force production.

The discharge of a spinal alpha motoneuron and the resulting contraction of its muscle fibres represents the functional quantum of the motor system. Recent advances in the recording and decomposition of the electromyographic signal allow for the identification of several tens of concurrently active motor units. These detailed population data provide the potential to achieve deep insights into the synaptic organization of motor commands. Yet most of our understanding of the synaptic input to motoneurons is derived from intracellular recordings in animal preparations. Thus, it is necessary to extend the new electrode and decomposition methods to recording of motor unit populations in these same preparations. To achieve this goal, we use high-density electrode arrays and decomposition techniques, analogous to those developed for humans, to record and decompose the activity of tens of concurrently active motor units in a hindlimb muscle in the in vivo cat. Our results showed that the decomposition method in this animal preparation was highly accurate, with conventional two-source validation providing rates of agreement equal to or superior to those found in humans. Multidimensional reconstruction of the motor unit action potential provides the ability to accurately track the same motor unit across multiple contractions. Additionally, correlational analyses demonstrate that the composite spike train provides better estimates of whole muscle force than conventional estimates obtained from the electromyographic signal. Lastly, stark differences are observed between the modes of activation, in particular tendon vibration produced quantal interspike intervals at integer multiples of the vibration period.

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.

The intrinsic excitability of spinal motoneurons is mediated in part by the presence of persistent inward currents (PICs), which amplify synaptic input and promote self-sustained firing. Studies using animal models have shown that PICs are greater in extensor motoneurons over flexor motoneurons, but this difference has not yet been demonstrated in humans. The primary objective of this study was to determine whether a similar difference exists in humans by recording from motor units in biceps and triceps brachii during isometric contractions. We compared firing rate profiles of pairs of motor units, in which the firing rate of the lower-threshold "control" unit was used as an indicator of common drive to the higher-threshold "test" unit. The estimated contribution of the PIC was calculated as the difference in firing rate of the control unit at recruitment versus derecruitment of the test unit, a value known as the delta-F (ΔF). We found that ΔF values were significantly higher in triceps brachii (5.4 ± 0.9 imp/s) compared with biceps brachii (3.0 ± 1.4 imp/s; P < 0.001). This difference was still present even after controlling for saturation in firing rate of the control unit, rate modulation of the control unit, and differences in recruitment time between test and control units, which are known to contribute to ΔF variability. We conclude that human elbow flexor and extensor motor units exhibit differences in intrinsic excitability, contributing to different neural motor control strategies between muscle groups.

Objective.-Noninvasive estimation of motoneuron excitability in human motoneurons is achieved through a paired motor unit analysis (ΔF) that quantifies hysteresis in the instantaneous firing rates at motor unit recruitment and de-recruitment. The ΔF technique provides insight into the magnitude of neuromodulatory synaptic input and persistent inward currents (PICs). While the ΔF technique is commonly used for estimating motoneuron excitability during voluntary contractions, computational parameters used for the technique vary across studies. A systematic investigation into the relationship between these parameters and ΔF values is necessary.Approach.-We assessed the sensitivity of the ΔF technique with several criteria commonly used in selecting motor unit pairs for analysis and methods used for smoothing the instantaneous motor 10

Motoneurons are unique in being the only neurons in the CNS whose firing patterns can be easily recorded in human subjects. This is because of the one-to-one relationship between the motoneuron and muscle cell behavior. It has long been appreciated that the connection of motoneurons to their muscle fibers allows their action potentials to be amplified and recorded, but only recently has it become possible to simultaneously record the firing pattern of many motoneurons via array electrodes placed on the skin. These firing patterns contain detailed information about the synaptic organization of motor commands to the motoneurons. This review focuses on parameters in these firing patterns that are directly linked to specific features of this organization. It is now well established that motor commands consist of three components, excitation, inhibition, and neuromodulation; the importance of the third component has become increasingly evident. Firing parameters linked to each of the three components are discussed, along with consideration of potential limitations in their utility for understanding the underlying organization of motor commands. Future work based on realistic computer simulations of motoneurons may allow quantitative "reverse engineering" of human motoneuron firing patterns to provide good estimates of the relative amplitudes and temporal patterns of all three components of motor commands.

Extra forces or torques are defined as forces or torques that are larger than would be expected from the input or stimuli, which can be mediated by properties intrinsic to motoneurons and/or to the muscle. The purpose of this study was to determine whether extra forces/torques evoked during electrical stimulation of the muscle or its nerve with variable frequency stimulation are modulated by muscle length/joint angle. A secondary aim was to determine whether extra forces/torques are generated by an intrinsic neuronal or muscle property. Experiments were conducted in 14 able-bodied human subjects and in eight adult decerebrate cats. Torque and force were measured in human and cat experiments, respectively. Extra forces/torques were evoked by stimulating muscles with surface electrodes (human experiments) or by stimulating the nerve with cuff electrodes (cat experiments). In humans and cats, extra forces/torques were larger at short muscle lengths, indicating that a similar regulatory mechanism is involved. In decerebrate cats, extra forces and length-dependent modulation were unaffected by intrathecal methoxamine injections, despite evidence of increased spinal excitability, and by transecting the sciatic nerve proximal to the nerve stimulations. Anesthetic nerve block experiments in two human subjects also failed to abolish extra torques and the length-dependent modulation. Therefore, these data indicate that extra forces/torques evoked during electrical stimulation of the muscle or nerve are muscle length-dependent and primarily mediated by an intrinsic muscle property.

Background Substantial data indicate greater muscle fatigue in individuals with spinal cord injury (SCI) compared with healthy control subjects when tested by using electrical stimulation protocols. Few studies have investigated the extent of volitional fatigue in motor incomplete SCI. Methods Repeated, maximal volitional effort (MVE) isometric contractions of the knee extensors (KE) were performed in 14 subjects with a motor incomplete SCI and in 10 intact subjects. Subjects performed 20 repeated, intermittent MVEs (5 seconds contraction/5 seconds rest) with KE torques and thigh electromyographic (EMG) activity recorded. Results Peak KE torques declined to 64% of baseline MVEs with repeated efforts in control subjects. Conversely, subjects with SCI increased peak torques during the first 5 contractions by 15%, with little evidence of fatigue after 20 repeated efforts. Increases in peak KE torques and the rate of torque increase during the first 5 contractions were attributed primarily to increases in quadriceps EMG activity, but not to decreased knee flexor co-activation. The observed initial increases in peak torque were dependent on the subject’s volitional activation and were consistent on the same or different days, indicating little contribution of learning or accommodation to the testing conditions. Sustained MVEs did not elicit substantial increases in peak KE torques as compared to repeated intermittent efforts. Conclusions These data revealed a marked divergence from expected results of increased fatigability in subjects with SCI, and may be a result of complex interactions between mechanisms underlying spastic motor activity and changes in intrinsic motoneuron properties.