CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA

Neural networks in the spinal cord control two basic features of locomotor movements: rhythm generation and pattern generation. Rhythm generation is generally considered to be dependent on glutamatergic excitatory neurons. Pattern generation involves neural circuits controlling left-right alternation, which has been described in great detail, and flexor-extensor alternation, which remains poorly understood. Here, we use a mouse model in which glutamatergic neurotransmission has been ablated in the locomotor region of the spinal cord. The isolated in?vitro spinal cord from these mice produces locomotor-like activity-when stimulated with neuroactive substances-with prominent flexor-extensor alternation. Under these conditions, unlike in control mice, networks of inhibitory interneurons generate the rhythmic activity. In the absence of glutamatergic synaptic transmission, the flexor-extensor alternation appears to be generated by Ia inhibitory interneurons, which mediate reciprocal inhibition from muscle proprioceptors to antagonist motor neurons. Our study defines a minimal inhibitory network that is needed to produce flexor-extensor alternation during locomotion.     

An EMG study of functional cortico-motoneuronal connections in humans.

We set out to decompose the EMG signal into its constituent motor unit action potential components to track motor unit firing rates with a high degree of accuracy and extract their average firing rate. We were able to show that this average firing rate tracks the subject's force trajectory from beginning to end. We propose that this average firing rate is a volitional control signal pointing to the existence of a 'volitional unit'. This volitional unit has to do with the projection of a group of functionally related cortico-motoneurons on a group of spinal motoneurons in the motoneuronal pool of a muscle. Our study of motor unit firing patterns during their steady state showed that spinal motoneurons respond to a descending central input in a Gaussian manner. We have further shown that the central drive itself, as represented by the average firing rate of the active motor units, also displays a Gaussian firing behavior. We have also described the existence of a 'translation factor', highly correlated to the motor unit size, which is unique to each spinal motoneuron and determines the motoneuronal response, and its resulting firing rate, to the descending inputs. As for force generation, we have shown that expressing the twitch force of a motor unit in a dynamic fashion using the 'electrotwitch' concept of firing rate x macro area, approximates motor unit force output better and accounts for firing rate related force changes more effectively than force estimates based on the mechanical twitch.     

Role of local nonspiking interneurons in the generation of rhythmic motor activity in the stick insect

Local nonspiking interneurons in the thoracic ganglia of insects are important premotor elements in posture control and locomotion. It was investigated whether these interneurons are involved in the central neuronal circuits generating the oscillatory motor output of the leg muscle system during rhythmic motor activity. Intracellular recordings from premotor nonspiking interneurons were made in the isolated and completely deafferented mesothoracic ganglion of the stick insect in preparations exhibiting rhythmic motor activity induced by the muscarinic agonist pilocarpine. All interneurons investigated provided synaptic drive to one or more motoneuron pools supplying the three proximal leg joints, that is, the thoraco-coxal joint, the coxa-trochanteral joint and the femur-tibia joint. During rhythmicity in 83% (n=67) of the recorded interneurons, three different kinds of synaptic oscillations in membrane potential were observed: (1) Oscillations were closely correlated with the activity of motoneuron pools affected; (2) membrane potential oscillations reflected only certain aspects of motoneuronal rhythmicity; and (3) membrane potential oscillations were correlated mainly with the occurrence of spontaneous recurrent patterns (SRP) of activity in the motoneuron pools. In individual interneurons membrane potential oscillations were associated with phase-dependent changes in the neuron's membrane conductance. Artificial changes in the interneurons' membrane potential strongly influenced motor activity. Injecting current pulses into individual interneurons caused a reset of rhythmicity in motoneurons. Furthermore, current injection into interneurons influenced shape and probability of occurrence for SRPs. Among others, identified nonspiking interneurons that are involved in posture control of leg joints were found to exhibit the above properties. From these results, the following conclusions on the role of nonspiking interneurons in the generation of rhythmic motor activity, and thus potentially also during locomotion, emerge: (1) During rhythmic motor activity most nonspiking interneurons receive strong synaptic drive from central rhythm-generating networks; and (2) individual nonspiking interneurons some of which underlie sensory-motor pathways in posture control, are elements of central neuronal networks that generate alternating activity in antagonistic leg motoneuron pools. © 1995 John Wiley & Sons, Inc.     

A Simulation Study to Examine the Effect of Common Motoneuron Inputs on Correlated Patterns of Motor Unit Discharge

The influence of common oscillatory inputs to the motoneuron pool on correlated patterns of motor unit discharge was examined using model simulations. Motor unit synchronization, in-phase fluctuations in mean firing rates known as ‘common drive’, and the coefficient of variation of the muscle force were examined as the frequency and amplitude of common oscillatory inputs to the motoneuron pool were varied. The amount of synchronization, the peak correlation between mean firing rates and the coefficient of variation of the force varied with both the frequency and amplitude of the common input signal. Values for ‘common drive’ and the force coefficient of variation were highest for oscillatory inputs at frequencies less than 5 Hz, while synchronization reached a maximum when the frequency of the common input was close to the average motor unit firing rate. The frequency of the common input signal for which the highest levels of synchronization were observed increased as motoneuron firing rates increased in response to higher target force levels. The simulation results suggest that common low-frequency oscillations in motor unit firing rates and short-term synchronization result from oscillatory activity in different bands of the frequency spectrum of shared motoneuron inputs. The results also indicate that the amount of synchronization between motor unit discharges depends not only on the amplitude of the shared input signal, but also on its frequency in relation to the present firing rates of the individual motor units.     

Syntheses of spinal cord field potentials in the terrapin

A compartmental model of a terrapin motoneuron has been set up to compute membrane potential variations associated with synaptic input at different locations or with antidromic invasion. Membrane potential distributions obtained in that way were used to compute field potentials by means of a volume conduction formalism. The model was used to simulated field potentials measured in the spinal cord in response to stimulation of a muscle nerve with the intention to discriminate between different activation hypothesis for the generation of the spinal cord potential. Extracellular potentials calculated with an excitatory input distributed over the whole dorsal dendritic tree were found to give better reconstruction when compared with excitation restricted to the distal part of the dorsal dendrites, or with somatic inhibition.     

The action of spike frequency adaptation in the postural motoneurons of hermit crab abdomen during the first phase of reflex activation

Cuticular strain associated with support of the shell of the hermit crab, Pagurus pollicarus, by its abdomen activates mechanoreceptors that evoke a stereotyped reflex in postural motoneurons. This reflex consists of three phases: a brief high-frequency burst of motoneuron spikes, a pause, and a much longer duration but lower frequency period of spiking. These phases are correlated with a rapid increase in muscle force followed by a slight decline to a level of tone that is greater than that at rest but less than maximal. The present experiments address the mechanisms underlying the transition from the first to second phase of the reflex and their role in force generation. Although centrally generated inhibitory post-synaptic potentials (IPSPS) are present during the pause period of the reflex, intracellular current injection of motoneurons reveals a spike frequency adaptation that rapidly and substantially reduces motoneuron firing frequency and is unchanged in saline that reduces synaptic transmission. The adaptation is voltage sensitive and persists for several hundred milliseconds upon repolarization. Hyperpolarization partially restores the initial response of the motoneuron to depolarizing current. Spike frequency adaptation and synaptic inhibition are important mechanisms in the generation of force that maintains abdominal stiffness at a constant, submaximal level.     

Probing the neuromodulatory gain control system in sports and exercise sciences

The monoaminergic bulbospinal pathways from the brainstem are central to motor functions by regulating the gains of spinal motoneurons and represent, in that respect, probably the primary control system for motoneuron excitability. Yet, the efficiency of this system is few, if not never, assessed in the fields of sports and exercise sciences. In this review paper, we propose a methodological approach intended to assess how this neuromodulatory system affects motoneuron excitability. This approach is based on the use of tendon vibration which can, in certain circumstances, induce the generation of the so-called tonic vibration reflex through the stimulation of muscle spindles. Force and EMG responses to tendon vibration are indeed indicative of how this descending system modulates the gain of the ionotropic inputs from Ia afferents and thus of the strength of the monoaminergic drive. After a brief presentation of the neuromodulatory system and of the mechanisms involved in the generation of the tonic vibration reflex, we address some important methodological considerations regarding the use of the TVR to probe this neuromodulatory gain control system. Hopefully, this paper will encourage sports and exercise scientists to investigate this system.     

Recurrent inhibition of human firing motoneurons (experimental and modeling study)

Recurrent inhibition between tonically activated single human motoneurons was studied experimentally and by means of a computer simulation. Motor unit activity was recorded during weak isometric constant-force muscle contractions of brachial biceps (BB) and soleus (SOL) muscles. Three techniques (cross correlogram, frequencygram, and interspike interval analysis) were used to gauge the relations between single motor unit potential trains. Pure inhibition was detected in 5.6% of 54 BB motoneuron pairs and in 5.2% of 43 SOL motoneuron pairs. In 27.8% (BB) and 23.7% (SOL) presumed inhibition symptoms were accompanied by a synchrony peak; 37% (BB) and 48.8% (SOL) exhibited synchrony alone. The demonstrated inhibition was very weak, at the edge of detectability. Computer simulations were based on the threshold-crossing model of a tonically firing motoneuron. The model included synaptic noise as well as threshold and postsynaptic potential (PSP) amplitude change within interspike interval. Inhibition efficiency of the model neurons increased with IPSP amplitude and duration, and with increasing source firing rate. The efficiency depended on target motoneuron interspike interval in a manner similar to standard deviation of ISI. The minimum detectable amplitude estimated in the simulations was about 50V, which, compared with the experimental results, suggests that amplitudes of detectable recurrent IPSPs in human motoneurons during weak muscle contractions do not exceed this magnitude. Since recurrent inhibition is known to be progressively depressed with an increase in the force of voluntary contraction, it is concluded that the recurrent inhibition hardly plays any important role in the isometric muscle contractions of constant force.     

Synaptic integration in motoneurons with hyper-excitable dendrites

Motoneurons have extensive dendritic trees that receive the numerous inputs required to produce movement. These dendrites are highly active, containing voltage-sensitive channels that generate persistent inward currents (PICs) that can enhance synaptic input 5-fold or more. However, this enhancement is proportional to the level of activity of monoaminergic inputs from the brainstem that release serotonin and noradrenalin. The higher this activity, the larger the dendritic PIC and the higher the firing rate evoked by a given amount of excitatory synaptic input. This brainstem control of motoneuron input-output gain translates directly into control of system gain of a motor pool and its muscle. Because large dendritic PICs are probably necessary for motoneurons to have sufficient gain to generate large forces, it is possible that descending monoaminergic inputs scale in proportion to voluntary force. Inhibition from sensory inputs has a strong suppressive effect on dendritic PICs: the stronger the inhibition, the smaller the PIC. Thus, local inhibitory inputs within the cord may oppose the descending monoaminergic control of PICs. Most motor behaviors evoke a mixture of excitation and inhibition (e.g., the reciprocal inhibition between antagonists). Therefore, normal joint movements may involve constant adjustment of PIC amplitude.     

Generation of locomotion rhythms without inhibition in vertebrates: the search for pacemaker neurons

Locomotion rhythms are thought to be generated by neurons in the central-pattern-generator (CPG) circuit in the spinal cord. Synaptic connections in the CPG and pacemaker properties in certain CPG neurons, both may contribute to generation of the rhythms. In the half-center model proposed by Graham Brown a century ago, reciprocal inhibition plays a critical role. However, in all vertebrate preparations examined, rhythmic motor bursts can be induced when inhibition is blocked in the spinal cord. Without inhibition, neuronal pacemaker properties may become more important in generation of the rhythms. Pacemaker properties have been found in motoneurons and some premotor interneurons in different vertebrates and they can be dependent on N-Methyl-d-aspartate (NMDA) receptors (NMDAR) or rely on other ionic currents like persistent inward currents. In the swimming circuit of the hatchling Xenopus tadpole, there is substantial evidence that emergent network properties can give rise to swimming rhythms. During fictive swimming, excitatory interneurons (dINs) in the caudal hindbrain fire earliest on each swimming cycle and their spikes drive the firing of other CPG neurons. Regenerative dIN firing itself relies on reciprocal inhibition and background excitation. We now find that the activation of NMDARs can change dINs from firing singly at rest to current injection to firing repetitively at swimming frequencies. When action potentials are blocked, some intrinsic membrane potential oscillations at about 10 Hz are revealed, which may underlie repetitive dIN firing during NMDAR activation. In confirmation of this, dIN repetitive firing persists in NMDA when synaptic transmission is blocked by Cd(2+). When inhibition is blocked, only dINs and motoneurons are functional in the spinal circuit. We propose that the conditional intrinsic NMDAR-dependent pacemaker firing of dINs can drive the production of swimming-like rhythms without the participation of inhibitory neurotransmission.     

Simulations of the alpha motoneuron pool electromyogram reflex at different preactivation levels in man

The alpha motoneuron pool and the surface electromyogram (EMG) of the human soleus muscle are modelled, respectively, by an alpha motoneuron pool model generating the firing patterns in the motor units of e muscle and by a muscle model using these discharge patterns to simulate the surface EMG. In the alpha motoneuron pool model, we use a population of motoneurons in which cellular properties like cell size and membrane conductance are distributed according to experimentally observed data. By calculating the contribution from each motor unit, the muscle model predicts the EMG. Wave forms of the motor unit action potentials in the surface EMG are obtained from experimental data. Using the model, we are able to give a quantitative prediction of the motoneuron pool activity and the reflex EMG output at different preactivation levels. The simulated data are consistent with experimentally obtained results in healthy humans. During static isometric muscle preactivations, the simulations show that the reflex strength is highly dependent on the intrinsic threshold properties of the alpha motoneuron pool. Received: 27 April 1993/Accepted in revised form: 8 September 1993     

Neuromechanisms of reciprocal interrelation between jaw-opening and jaw-closing muscles in the cat (author's transl)]

Neural controlling mechanisms between the digastric (jaw-opening) and masseter (jaw-closing) muscles were studied in the cat. High threshold afferent impulses from the anterior belly of the digastric muscle to masseteric montoneurons in the trigeminal motor nucleus induced an EPSP-IPSP sequence of potentials with long latency, and high threshold afferent impulses from the masseter muscle also exerted a similar effect on digastric motoneurons in the same nucleus innervating the anterior belly of the digastric muscle. These results suggest that reciprocal inhibition via Ia interneurons as observed between the flexor and extensor muscles in the spinal cord does not exist between the digastric and masseter muscles in the cat. However, the respective motoneurons innervating the masseter and digastric muscles receive inputs of early excitation-late inhibition via high threshold afferent nerve fibers from each antagonistic muscle. As such, since EPSPs preceding IPSPs are recognized, these high threshold afferent impulses may exert not only a reciprocal inhibitory effect, but also a synchronous excitatory or inhibitory effect on the antagonistic motoneurons.     

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.     

Ethanol influences on the chick embryo spinal cord motor system: Analyses of motoneuron cell death,motility, and target trophic factor activity and in vitro analyses of neurotoxicity and trophic factor neuroprotection

A series of in vivo and in vitro experiments were conducted to determine the influence of prenatally administered ethanol on several aspects of the developing chick embryo spinal cord motor system. Specifically, we examined: (1) the effect of chronic ethanol administration during the natural cell death period on spinal cord motoneuron numbers; (2) the influence of ethanol on ongoing embryonic motility; (3) the effect of ethanol exposure on neurotrophic activity in motoneuron target tissue (limbbud); and (4) the responsiveness of cultured spinal cord neurons to ethanol, and the potential of target-derived neurotrophic factors to ameliorate ethanol neurotoxicity. These studies revealed the following: Chronic prenatal ethanol exposure reduces the number of motoneurons present in the lateral motor column after the cell death period [embryonic day 12 (E12)]. Ethanol tends to inhibit embryonic motility, particularly during the later stages viewed (E9-E11). Chronic ethanol exposure reduces the neurotrophic activity contained in target muscle tissue. Such diminished support could contribute to the observed motoneuron loss. Direct exposure of spinal cord neurons to ethanol decreases neuronal survival and process outgrowth in a dose-dependent manner, but the addition of target muscle extract to ethanol-containing cultures can ameliorate this ethanol neurotoxicity. These studies demonstrate ethanol toxicity in a population not previously viewed in this regard and suggest a mechanism that may be related to this cell loss (i.e., decreased neurotrophic support). © 1995 John Wiley & Sons, Inc.     

Partly shared spinal cord networks for locomotion and scratching

Animals produce a variety of behaviors using a limited number of muscles and motor neurons. Rhythmic behaviors are often generated in basic form by networks of neurons within the central nervous system, or central pattern generators (CPGs). It is known from several invertebrates that different rhythmic behaviors involving the same muscles and motor neurons can be generated by a single CPG, multiple separate CPGs, or partly overlapping CPGs. Much less is known about how vertebrates generate multiple, rhythmic behaviors involving the same muscles. The spinal cord of limbed vertebrates contains CPGs for locomotion and multiple forms of scratching. We investigated the extent of sharing of CPGs for hind limb locomotion and for scratching. We used the spinal cord of adult red-eared turtles. Animals were immobilized to remove movement-related sensory feedback and were spinally transected to remove input from the brain. We took two approaches. First, we monitored individual spinal cord interneurons (i.e., neurons that are in between sensory neurons and motor neurons) during generation of each kind of rhythmic output of motor neurons (i.e., each motor pattern). Many spinal cord interneurons were rhythmically activated during the motor patterns for forward swimming and all three forms of scratching. Some of these scratch/swim interneurons had physiological and morphological properties consistent with their playing a role in the generation of motor patterns for all of these rhythmic behaviors. Other spinal cord interneurons, however, were rhythmically activated during scratching motor patterns but inhibited during swimming motor patterns. Thus, locomotion and scratching may be generated by partly shared spinal cord CPGs. Second, we delivered swim-evoking and scratch-evoking stimuli simultaneously and monitored the resulting motor patterns. Simultaneous stimulation could cause interactions of scratch inputs with subthreshold swim inputs to produce normal swimming, acceleration of the swimming rhythm, scratch-swim hybrid cycles, or complete cessation of the rhythm. The type of effect obtained depended on the level of swim-evoking stimulation. These effects suggest that swim-evoking and scratch-evoking inputs can interact strongly in the spinal cord to modify the rhythm and pattern of motor output. Collectively, the single-neuron recordings and the results of simultaneous stimulation suggest that important elements of the generation of rhythms and patterns are shared between locomotion and scratching in limbed vertebrates.     

Simultaneous Intracellular Recording of a Lumbar Motoneuron and the Force Produced by its Motor Unit in the Adult Mouse In vivo

The spinal motoneuron has long been a good model system for studying neural function because it is a neuron of the central nervous system with the unique properties of (1) having readily identifiable targets (the muscle fibers) and therefore having a very well-known function (to control muscle contraction); (2) being the convergent target of many spinal and descending networks, hence the name of "final common pathway"; and (3) having a large soma which makes it possible to penetrate them with sharp intracellular electrodes. Furthermore, when studied in vivo, it is possible to record simultaneously the electrical activity of the motoneurons and the force developed by their muscle targets. Performing intracellular recordings of motoneurons in vivo therefore put the experimentalist in the unique position of being able to study, at the same time, all the compartments of the "motor unit" (the name given to the motoneuron, its axon, and the muscle fibers it innervates¹): the inputs impinging on the motoneuron, the electrophysiological properties of the motoneuron, and the impact of these properties on the physiological function of the motoneurons, i.e. the force produced by its motor unit. However, this approach is very challenging because the preparation cannot be paralyzed and thus the mechanical stability for the intracellular recording is reduced. Thus, this kind of experiments has only been achieved in cats and in rats. However, the study of spinal motor systems could make a formidable leap if it was possible to perform similar experiments in normal and genetically modified mice.For technical reasons, the study of the spinal networks in mice has mostly been limited to neonatal in vitro preparations, where the motoneurons and the spinal networks are immature, the motoneurons are separated from their targets, and when studied in slices, the motoneurons are separated from most of their inputs. Until recently, only a few groups had managed to perform intracellular recordings of motoneurons in vivo^2-4 , including our team who published a new preparation which allowed us to obtain very stable recordings of motoneurons in vivo in adult mice^5,6. However, these recordings were obtained in paralyzed animals, i.e. without the possibility to record the force output of these motoneurons. Here we present an extension of this original preparation in which we were able to obtain simultaneous recordings of the electrophysiological properties of the motoneurons and of the force developed by their motor unit. This is an important achievement, as it allows us to identify the different types of motoneurons based on their force profile, and thereby revealing their function. Coupled with genetic models disturbing spinal segmental circuitry^7-9, or reproducting human disease^10,11, we expect this technique to be an essential tool for the study of spinal motor system.     

The resilience of the size principle in the organization of motor unit properties in normal and reinnervated adult skeletal muscles

Henneman's size principle relates the input and output properties of motoneurons and their muscle fibers to size and is the basis for size-ordered activation or recruitment of motor units during movement. After nerve injury and surgical repair, the relationship between motoneuron size and the number and size of the muscle fibers that the motoneuron reinnervates is initially lost but returns with time, irrespective of whether the muscles are self- or cross-reinnervated by the regenerated axons. Although the return of the size relationships was initially attributed to the recovery of the cross-sectional area of the reinnervated muscle fibers and their force per fiber, direct enumeration of the innervation ratio and the number of muscle fibers per motoneuron demonstrated that a size-dependent branching of axons accounts for the size relationships in normal muscle, as suggested by Henneman and his colleagues. This same size-dependent branching accounts for the rematching of motoneuron size and muscle unit size in reinnervated muscles. Experiments were carried out to determine whether the daily amount of neuromuscular activation of motor units accounts for the size-dependent organization and reorganization of motor unit properties. The normal size-dependent matching of motoneurons and their muscle units with respect to the numbers of muscle fibers per motoneuron was unaltered by synchronous activation of all of the motor units with the same daily activity. Hence, the restored size relationships and rematching of motoneuron and muscle unit properties after nerve injuries and muscle reinnervation sustain the normal gradation of muscle force during movement by size-ordered recruitment of motor units and the process of rate coding of action potentials. Dynamic modulation of size of muscle fibers and their contractile speed and endurance by neuromuscular activity allows for neuromuscular adaptation in the context of the sustained organization of the neuromuscular system according to the size principle.     

Effects of sustained stimulation on the excitability of motoneurons innervating paralyzed and control muscles.

The excitability of thenar motoneurons (reflected by F-wave persistence and amplitude) and thenar muscle force were measured during a stimulation protocol (90 s of 18-Hz supramaximal electrical stimulation of the median nerve) designed to induce muscle fatigue (force decline). Data from muscles (n = 15) paralyzed by chronic cervical spinal cord injury were compared with those obtained from control muscles (n = 6). The persistence of F waves in both paralyzed and control muscles increased from approximately 60 to approximately 76% during the first 10 s of the fatigue protocol. Persistence then declined progressively to approximately 33% at 90 s. These changes in F-wave persistence suggest that similar reductions occur in the excitability of the motoneurons to paralyzed and control motor units after sustained antidromic activation. Despite this, significantly larger force declines occurred in the paralyzed muscles of spinal cord-injured subjects (approximately 60%) than in the muscles of control subjects (approximately 15%). These data suggest that the decreases in motoneuron excitability for both the spinal cord-injured and control subjects are a result of activity-dependent changes in motoneuron properties that are independent of fatigue-related processes in the muscles.     

Rate-coding of spinal motoneurons with high-frequency magnetic stimulation of human motor cortex

Rate-coding in spinal motoneurons was studied using high-frequency magnetic stimulation of the human motor cortex. The subject made a weak contraction to cause rhythmic (i.e., tonic) discharge of a single motor unit in flexor (or extensor) carpi radialis or tibialis anterior, while the motor cortical representation of that muscle was stimulated with brief trains of pulses from a Pyramid stimulator (4 Magstim units connected by 3 BiStim modules). An "m@n" stimulus train consisted of m number of pulses (1-4), with an interpulse interval (IPI) of n ms (1-6). Peristimulus time histograms were constructed for each stimulus condition of a given motor unit, and related to the average rectified surface electromyography (EMG) from that muscle. Surface EMG responses showed markedly more facilitation than single-pulse stimulation, with increasing numbers of pulses in the train; responses also tended to increase in magnitude for the longer IPI values (4 and 6 ms) tested. Motor-unit response probability increased in a manner comparable to that of surface EMG. In particular, motoneurons frequently responded twice to a given stimulus train. In addition to recruitment of new motor units, the increased surface EMG responses were, in part, a direct consequence of short-term rate-coding within the tonically discharging motoneuron. Our results suggest that human corticomotoneurons are capable of reliably following high-frequency magnetic stimulation rates, and that this activity pattern is carried over to the spinal motoneuron, enabling it to discharge at extremely high rates for brief periods of time, a pattern known to be optimal for force generation at the onset of a muscle contraction.