Tibialis Anterior Motoneurons Research Articles

Intrinsic motoneuron properties in typical human development.

Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators such as serotonin. Here, we examined the age-related development of self-sustained firing and general excitability of tibialis anterior motoneurons in a young development (7-17years), young adult (18-28years) and adult (32-53years) group, as well as in a separate group of participants taking selective serotonin reuptake inhibitors (SSRIs, aged 11-28years). Self-sustained firing, as measured by ΔF, was larger in the young development (∼5.8Hz, n=20) compared to the young adult (∼4.9Hz, n=13) and adult (∼4.8Hz, n=8) groups, consistent with a developmental decrease in self-sustained firing mediated by persistent inward currents (PIC). ΔF was also larger in participants taking SSRIs (∼6.5Hz, n=9) compared to their age-matched controls (∼5.3Hz, n=26), consistent with increased levels of spinal serotonin facilitating the motoneuron PIC. Participants in the young development and SSRI groups also had higher firing rates and a steeper acceleration in initial firing rates (secondary ranges), consistent with the PIC producing a steeper acceleration in membrane depolarization at the onset of motoneuron firing. In summary, both the young development and SSRI groups exhibited increased intrinsic motoneuron excitability compared to the adults, which, in the young development group, was also associated with a larger unsteadiness in the dorsiflexion torque profiles. We propose several intrinsic and extrinsic factors that affect both motoneuron PICs and cell discharge which vary during development, with a time course similar to the changes in motoneuron firing behaviour observed in the present study. KEY POINTS: Neurons in the spinal cord that activate muscles in the limbs (motoneurons) undergo increases in excitability shortly after birth to help animals stand and walk. We examined whether the excitability of human ankle flexor motoneurons also continues to change from child to adulthood by recording the activity of the muscle fibres they innervate. Motoneurons in children and adolescents aged 7-17years (young development group) had higher signatures of excitability that included faster firing rates and more self-sustained activity compared to adults aged ≥18years. Participants aged 11-28years of age taking serotonin reuptake inhibitors had the highest measures of motoneuron excitability compared to their age-matched controls. The young development group also had more unstable contractions, which might partly be related to the high excitability of the motoneurons.

BDNF Spinal Overexpression after Spinal Cord Injury Partially Protects Soleus Neuromuscular Junction from Disintegration, Increasing VAChT and AChE Transcripts in Soleus but Not Tibialis Anterior Motoneurons.

After spinal cord transection (SCT) the interaction between motoneurons (MNs) and muscle is impaired, due to reorganization of the spinal network after a loss of supraspinal inputs. Rats subjected to SCT, treated with intraspinal injection of a AAV-BDNF (brain-derived neurotrophic factor) construct, partially regained the ability to walk. The central effects of this treatment have been identified, but its impact at the neuromuscular junction (NMJ) has not been characterized. Here, we compared the ability of NMJ pre- and postsynaptic machinery in the ankle extensor (Sol) and flexor (TA) muscles to respond to intraspinal AAV-BDNF after SCT. The gene expression of cholinergic molecules (VAChT, ChAT, AChE, nAChR, mAChR) was investigated in tracer-identified, microdissected MN perikarya, and in muscle fibers with the use of qPCR. In the NMJs, a distribution of VAChT, nAChR and Schwann cells was studied by immunofluorescence, and of synaptic vesicles and membrane active zones by electron microscopy. We showed partial protection of the Sol NMJs from disintegration, and upregulation of the VAChT and AChE transcripts in the Sol, but not the TA MNs after spinal enrichment with BDNF. We propose that the observed discrepancy in response to BDNF treatment is an effect of difference in the TrkB expression setting BDNF responsiveness, and of BDNF demands in Sol and TA muscles.

Looking at the bigger PICture: understanding and counteracting the decline of persistent inward currents in older adults.

Looking at the bigger PICture: understanding and counteracting the decline of persistent inward currents in older adults.

Spinal motor mapping by epidural stimulation of lumbosacral posterior roots in humans.

SummaryEpidural electrical stimulation of the spinal cord is an emergent strategy for the neurological recovery of lower-extremity motor function. Motoneuron pools are thought to be recruited by stimulation of posterior roots. Here, we linked electromyographic data of epidurally evoked lower-extremity responses of 34 individuals with upper motoneuron disorders to a population model of the spinal cord constructed using anatomical parameters of thousands of individuals. We identified a relationship between segmental stimulation sites and activated spinal cord segments, which made spinal motor mapping from epidural space possible despite the complex anatomical interface imposed by the posterior roots. Our statistical approach provided evidence for low-threshold sites of posterior roots and effects of monopolar and bipolar stimulation previously predicted by computer modeling and allowed us to test the impact of different upper motoneuron disorders on the evoked responses. Finally, we revealed a statistical association between intraoperative and postoperative mapping of the spinal cord.

Gait-combined transcranial alternating current stimulation modulates cortical control of muscle activities during gait.

Non-invasive brain stimulation has been of interest as a therapeutic tool to modulate cortical excitability. However, there is little evidence that oscillatory brain stimulation can modulate the cortical control of muscle activities during gait, which can be assessed using coherence analysis of paired surface electromyographic (EMG) recordings. This study aimed to investigate the effects of gait-combined transcranial alternating current stimulation (tACS) at the gait cycle frequency on the cortical control of muscle activities during gait using EMG-EMG coherence analysis. Fourteen healthy young adults participated in this study. All participants underwent 2 test conditions (real tACS and sham stimulation over the leg area of the primary motor cortex during 10-min treadmill walking). The average peak-to-peak amplitudes of the motor evoked potentials (MEPs) from the tibialis anterior (TA) and lateral gastrocnemius muscles in the sitting position and EMG-EMG coherences in the TA muscle, triceps surae muscles, quadriceps muscles, and hamstring muscles during gait were measured before and after stimulation. Entrainment effect was significantly higher during real tACS than during sham stimulation. After real tACS, the MEP amplitude and beta band (13-33Hz) coherence area increased in the TA muscle. The change in MEP amplitude from the TA muscle was positively correlated with the change in beta band coherence area in the TA muscle. Gait-combined tACS can modulate the strength of descending neural drive to TA motoneurons during gait. This suggests that oscillatory brain stimulation is a useful therapeutic tool to modulate the cortical control of muscle activities during gait.

Alteration of glycinergic receptor expression in lumbar spinal motoneurons is involved in the mechanisms underlying spasticity after spinal cord injury

Spasticity is a disabling motor disorder affecting 70% of people with brain and spinal cord injury. The rate-dependent depression (RDD) of the H reflex is the only electrophysiological measurement correlated with the degree of spasticity assessed clinically in spastic patients. Several lines of evidence suggest that the mechanism underlying the H reflex RDD depends on the strength of synaptic inhibition through GABAA (GABAAR) and glycine receptors (GlyR). In adult rats with spinal cord transection (SCT), we studied the time course of the expression of GABAAR and GlyR at the membrane of retrogradely identified Gastrocnemius and Tibialis anterior motoneurons (MNs) 3, 8 and 16 weeks after injury, and measured the RDD of the H reflex at similar post lesion times. Three weeks after SCT, a significant decrease in the expression of GABAA and GlyR was observed compared to intact rats, and the H-reflex RDD was much less pronounced than in controls. Eight weeks after SCT, GlyR values returned to normal. Simultaneously, we observed a tendency to recover normal RDD of the H reflex at higher frequencies. We tested whether an anti-inflammatory treatment using methylprednisolone performed immediately after SCT could prevent alterations in GABAA/glycine receptors and/or the development of spasticity observed 3 weeks after injury. This treatment restored control levels of GlyR but not the expression of GABAAR, and it completely prevented the attenuation of RDD. These data strongly suggest that alteration of glycinergic inhibition of lumbar MNs is involved in the mechanisms underlying spasticity after SCI.

Gait-synchronized oscillatory brain stimulation modulates common neural drives to ankle muscles in patients after stroke: A pilot study

The present study aimed to investigate the long-term effects of gait intervention with transcranial alternating current stimulation (tACS) synchronized with gait cycle frequency on the cortical control of muscle activity during gait, using coherence analyses, in patients after stroke. Eight chronic post-stroke patients participated in a single-blinded crossover study, and 7 patients completed the long-term intervention. Each patient received tACS over the primary motor cortex foot area on the affected side, which was synchronized with individual gait cycle frequency, and sham stimulation during treadmill gait in a random order. Electrical neuromuscular stimulation was used to assist the paretic ankle movement in both conditions. After gait intervention with tACS, beta band (15−35 Hz) coherence, which is considered to have a cortical origin, significantly increased in the paretic tibialis anterior (TA) muscle during 6-min of over-ground gait. The change in beta band coherence in the paretic TA muscle was positively correlated with the change in gait distance. These results indicate that gait intervention with tACS synchronized with gait cycle frequency may induce gait-specific plasticity that modulates the common neural drive to the TA motoneurons on the paretic side during gait and leads to changes in gait function in patients after stroke.

Changes in innervation of lumbar motoneurons and organization of premotor network following training of transected adult rats

Rats with complete spinal cord transection (SCT) can recover hindlimb locomotor function under strategies combining exercise training and 5-HT agonist treatment. This recovery is expected to result from structural and functional re-organization within the spinal cord below the lesion. To begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (GS) or tibialis anterior (TA) motoneurons (MNs) in SCT rats after a schedule of early exercise training and delayed 5-HT agonist treatment. In addition, we analyzed changes in distribution and number of lumbar interneurons (INs) presynaptic to GS MNs using retrograde transneuronal transport of rabies virus.In SCT-untrained rats, we found few changes in the density and size of inhibitory and excitatory inputs impinging on cell bodies of TA and GS MNs compared to intact rats, whereas there was a marked trend for a reduction in the number of premotor INs connected to GS MNs. In contrast, after training of SCT rats, a significant increase of the density of GABAergic and glycinergic axon terminals was observed on both GS and TA motoneuronal cell bodies, as well as of presynaptic P-boutons on VGLUT1 afferents. Despite these changes in innervation the number of premotor INs connected to GS MNs was similar to control values although some new connections to MNs were observed. These results suggest that adaptation of gait patterns in SCT-trained rats was accompanied by changes in the innervation of lumbar MNs while the distribution of the spinal premotor circuitry was relatively preserved.

Effects of transcranial alternating current stimulation on common neural drive to motoneurons during gait in healthy young adults

Background: Non-invasive brain stimulation, such as transcranial direct current stimulation, has been of interest as a therapeutic tool to modulate cortical excitability. However, there is little evidence that such stimulation during gait can modulate the corticospinal control of human walking. Since previous reports revealed the rhythmic activation of human motor cortex during gait, it is expected that oscillatory brain stimulation, such as transcranial alternating current stimulation (tACS), canmodulate the cortical control of muscle activities during gait. Recently, coherence analysis of paired surface electromyography (EMG) has been used to quantitatively evaluate the common neural drive from the motor cortex to spinal motoneurons during gait, which can be applied to investigate the corticospinal control of walking. Purpose: This study aimed to investigate the effects of tACS during gait on corticospinal excitability and EMG/EMG coherence in healthy young adults. Methods: Ten healthy young adults participated in this study. All participants received tACS over the leg area of the left primary motor cortex (M1) during treadmill walking for 10minutes. They also performed treadmill walking for 5minutes before and after tACS to measure surface EMG. TACS with a current intensity of 2mA (ranging from −1 to 1mA) was applied for 10min at the frequency that corresponds to the gait cycle during treadmill walking before tACS (0.87± 0.60Hz). To evaluate corticospinal excitability, transcranialmagnetic stimulationwas applied over the leg area of the left M1 before and after tACS. The averages of 10 peak-to-peak amplitudes of motor evoked potentials (MEPs) of fixed intensity (SI 1mV)weremeasured from the right tibialis anterior (TA) and lateral gastrocnemius (LG) muscles. To evaluate the common neural drive to muscles, EMG/EMG coherence was calculated from the following muscle pairs: the proximal and distal ends of the TA muscle (TA-TA) and the LG and medialis gastrocnemius muscles (LG-MG) on the right leg. The areas of coherence curve were calculated in the beta (13–30Hz) and gamma (30–60Hz) frequency bands before and after tACS. MEP amplitudes from the TA and LG muscles before and after tACS were compared. The relationships between MEP amplitude changes and changes in the area of beta and gamma-band EMG/EMG coherence of each muscle were investigated. Results:MEP amplitudes in the TA muscle were significantly increased after tACS, although therewas no significant change in MEP amplitudes in the LG muscle. There was a significant positive correlation between change in MEP amplitude of the TA muscle and change in area of beta-band TA-TA coherence. Conclusion(s): TACS increased corticospinal excitability in the TA muscle. Furthermore, tACS also induced gaitspecific plasticity that modulated the neural drive from M1 to TA motoneurons during gait, corresponding to changes in corticospinal excitability in the TA muscle. Implications: TACS can modulate the common neural drive from the motor cortex to spinal motoneurons during gait and may be an effective tool for improving gait function in patients with central nervous system disorders.

Long-latency, inhibitory spinal pathway to ankle flexors activated by homonymous group 1 afferents

Inhibitory feedback from sensory pathways is important for controlling movement. Here, we characterize, for the first time, a long-latency, inhibitory spinal pathway to ankle flexors that is activated by low-threshold homonymous afferents. To examine this inhibitory pathway in uninjured, healthy participants, we suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50, and 60 ms earlier and at intensities of 0.5-0.7 times motor threshold (average suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below M-wave and H-reflex threshold, it produced a long-latency inhibition of background muscle activity, approximately 65-115 ms after the CPN stimulation, a time period that overlapped with the test MEP. However, not all of the MEP suppression could be accounted for by this decrease in background muscle activity. Evoked responses from direct activation of the corticospinal tract, at the level of the brain stem or thoracic spinal cord, were also suppressed by low-threshold CPN stimulation. Our findings suggest that low-threshold muscle and cutaneous afferents from the CPN activate a long-latency, homonymous spinal inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from spinal networks, activated by low-threshold homonymous afferents, helps regulate the activation of flexor motoneurons by the corticospinal tract.

Spinal plasticity in stroke patients after botulinum neurotoxin A injection in ankle plantar flexors

The effect of botulinum neurotoxin A (BoNT-A) in stroke patients' upper limbs has been attributed to its peripheral action only. However, BoNT-A depressed recurrent inhibition of lumbar motoneurons, likely due to its retrograde transportation along motor axons affecting synapses to Renshaw cells. Because Renshaw cells control group Ia interneurons mediating reciprocal inhibition between antagonists, we tested whether this inhibition, particularly affected after stroke, could recover after BoNT-A. The effect of posterior tibial nerve (PTN) stimulation on tibialis anterior (TA) electromyogram (EMG) was investigated in 13 stroke patients during treadmill walking before and 1 month after BoNT-A injection in ankle plantar flexors. Before BoNT-A, PTN stimuli enhanced TA EMG all during the swing phase. After BoNT-A, the PTN-induced reciprocal facilitation in TA motoneurons was depressed at the beginning of swing and reversed into inhibition in midswing, but at the end of swing, the reciprocal facilitation was enhanced. This suggests that BoNT-A induced spinal plasticity leading to the recovery of reciprocal inhibition likely due to the withdrawal of inhibitory control from Renshaw cells directly blocked by the toxin. At the end of swing, the enhanced reciprocal facilitation might be due to BoNT-induced modification of peripheral afferent inputs. Therefore, both central and peripheral actions of BoNT-A can modify muscle synergies during walking: (1) limiting ankle muscle co-contraction in the transition phase from stance to swing, to assist dorsiflexion, and (2) favoring it from swing to stance, which blocks the ankle joint and thus assists the balance during the single support phase on the paretic limb.

Failure of normal development of central drive to ankle dorsiflexors relates to gait deficits in children with cerebral palsy

Neurophysiological markers of the central control of gait in children with cerebral palsy (CP) are used to assess developmental response to therapy. We measured the central common drive to a leg muscle in children with CP. We recorded electromyograms (EMGs) from the tibialis anterior (TA) muscle of 40 children with hemiplegic CP and 42 typically developing age-matched controls during static dorsiflexion of the ankle and during the swing phase of treadmill walking. The common drive to TA motoneurons was identified through time- and frequency-domain cross-correlation methods. In control subjects, the common drive consists of frequencies between 1 and 60 Hz with peaks at beta (15-25 Hz) and gamma (30-45 Hz) frequencies known to be caused by activity within sensorimotor cortex networks: this drive to motoneurons strengthens during childhood. Similar to this drive in control subjects, this drive to the least affected TA in the CP children tended to strengthen with age, although compared with that in the control subjects, it was slightly weaker. For CP subjects of all ages, the most affected TA muscle common drive was markedly reduced compared with that of their least affected muscle as well as that of controls. These differences between the least and most affected TA muscles were unrelated to differences in the magnitude of EMG in the two muscles but positively correlated with ankle dorsiflexion velocity and joint angle during gait. Time- and frequency-domain analysis of ongoing EMG recruited during behaviorally relevant lower limb tasks provides a noninvasive and important measure of the central drive to motoneurons in subjects with CP.

Different effects of spinalization and locomotor training of spinal animals on cholinergic innervation of the soleus and tibialis anterior motoneurons

Cholinergic input modulates excitability of motoneurons and plays an important role in the control of locomotion in both intact and spinalized animals. However, spinal cord transection in adult rats affects cholinergic innervation of only some hindlimb motoneurons, suggesting that specificity of this response is related to functional differences between motoneurons. Our aim was therefore to compare cholinergic input to motoneurons innervating the soleus (Sol) and tibialis anterior (TA) motoneurons following spinal cord transection at a low-thoracic level. The second aim was to investigate whether deficits in cholinergic input to these motoneurons could be modified by locomotor training. The Sol and TA motoneurons were identified by retrograde labelling with fluorescent dyes injected intramuscularly. Cholinergic terminals were detected using anti-vesicular acetylcholine transporter (VAChT) antibody. Overall innervation of motoneurons was evaluated with anti-synaptophysin antibody. After spinalization we found a decrease in the number of VAChT-positive boutons apposing perikarya of the Sol (to 49%) but not TA motoneurons. Locomotor training, resulting in moderate functional improvement, partly reduced the deficit in cholinergic innervation of Sol motoneurons by increasing the number of VAChT-positive boutons. However, the optical density of VAChT-positive boutons terminating on various motoneurons, which decreased after spinalization, continued to decrease despite the training, suggesting an impairment of acetylcholine availability in the terminals. Different effects of spinal cord transection on cholinergic innervation of motoneurons controlling the ankle extensor and flexor muscles point to different functional states of these muscles in paraplegia as a possible source of activity-dependent signaling regulating cholinergic input to the motoneurons.

Locomotor Training Maintains Normal Inhibitory Influence on Both Alpha- and Gamma-Motoneurons after Neonatal Spinal Cord Transection

Spinal cord injuries lead to impairments, which are accompanied by extensive reorganization of neuronal circuits caudal to the injury. Locomotor training can aid in the functional recovery after injury, but the neuronal mechanisms associated with such plasticity are only sparsely known. We investigated ultrastructurally the synaptic inputs to tibialis anterior motoneurons (MNs) retrogradely labeled in adult rats that had received a complete midthoracic spinal cord transection at postnatal day 5. A subset of the injured rats received locomotor training. Both γ- and α-MNs were studied. The total number of boutons apposing γ-MNs, but not α-MNs, was reduced after neonatal spinal cord transection. The proportion of inhibitory to excitatory boutons, however, was increased significantly in both α-MNs and γ-MNs in spinally transected rats, but with locomotor training returned to levels observed in intact rats. The specific densities and compositions of synaptic boutons were, however, different between all three groups. Surprisingly, we observed the atypical presence of both C- and M-type boutons apposing the somata of γ-MNs in the spinal rats, regardless of training status. We conclude that a neonatal spinal cord transection induces significant reorganization of synaptic inputs to spinal motoneurons caudal to the site of injury with a net increase in inhibitory influence, which is associated with poor stepping. Spinal cord injury followed by successful locomotor training, however, results in improved bipedal stepping and further synaptic changes with the proportion of inhibitory and excitatory inputs to the motoneurons being similar to that observed in intact rats.

Recovery of human motoneurons during rotation

During prolonged contractions, few studies have reported rotation among low threshold motoneurons. The question arises whether a motoneuron stops firing due to an increase in firing threshold or whether it is due to regional switching of activity among muscle fascicles. We postulated that if the rest period resulted from an increase in firing threshold, a progressive recovery in the excitability of the motoneuron would be observed during the rest period. The excitability of soleus or tibialis anterior motoneurons was tested during the rest periods. The results showed that a previously tonic motoneuron that had dropped off during rotation, rarely responded to Ia or TMS inputs in the initial parts of the rest period; however, its response probability increased significantly in the second half. Based on these data, we suggest that the observed rotation is due to changes in firing thresholds of motoneurons during prolonged firing.

Ice Application Effects on Peroneus Longus and Tibialis Anterior Motoneuron Excitability in Subjects with Functional Ankle Instability

ABSTRACTEvidence that focally cooling the ankle joint facilitates soleus and peroneus longus spinal reflex activity in healthy subjects has been reported. This response has been confirmed in individuals with a history of joint pathology for the soleus but not in the peroneus longus and tibialis anterior. The purpose of this study was to identify the effects of ankle cooling on isokinetic eversion and inversion torque and in peroneus longus, tibialis anterior H-reflex (Hmax:Mmax) in subjects with functional ankle instability (FAI). Twenty-four college aged subjects volunteered for this study. Peroneus longus and tibialis anterior Hmax:Mmax, and concentric eversion and inversion torque were recorded prior to and following each session. This protocol was used to compare FAI to healthy ankle group. There were no significant differences between groups. There were weak and no significant relationships between the corresponding muscles motoneuron excitability and their peak torque measurements. Ice application to the joint did not alter the peroneus longus or the tibialis anterior.

Functional involvement of the lumbar spinal cord after contusion to T8 spinal segment of the rat

To evaluate the effects on locomotion and lumbar motoneuron function after a contusion to the midthoracic spinal cord of the rat. Five animals received a moderate contusion on T8, and over 28 days postoperation (dpo) locomotion and motor electrophysiological outcome were compared with five sham-operated animals. At 28 dpo, the contused animals supported their body weight (BBB score =11.5 ± 0.5) and stepped uncoordinatedly. Motor evoked potentials recorded in the tibialis anterior (TA) and plantar muscles (PL), and longitudinal interlimb reflexes recorded in the TA muscles were abolished. The M wave recorded in the TA showed a decrease in amplitude by 7 dpo, which remained invariable until the end of the evaluation (88 ± 3% of {preoperative} values), whereas in the PL muscle it was not affected. Injured animals presented hyperreflexia, as shown by an increased H/M ratio. Histological analysis showed similar number of retrogradely traced TA motoneurons between groups, and that contused animals presented hypertrophied astrocytes in the most rostral but not caudal segments of the lumbar enlargement. These results indicate that after contusion to the thoracic spinal cord, the lumbar segments undergo structural and functional changes, following a rostro-caudal gradient extension.

Seeking functions for spinal recurrent inhibition

In this issue of The Journal of Physiology, Lamy et al. (2008) describe a rhythmic modulation of recurrent inhibition during walking in man. This provides some insight into the function of recurrent inhibition, first described by Renshaw (1941) as an inhibition of cat motoneurones produced by antidromic stimulation of the axons of neighbouring motoneurones (homonymous action). Subsequent work, also in cats, showed that motor axon collaterals activate interneurones (the eponymous Renshaw cells) that in turn inhibit motoneurones. Actions extend to more distant muscle groups (heteronymous) and parallel the pattern of heteronymous monosynaptic excitation from muscle spindle Ia afferents. Renshaw cells receive peripheral sensory and descending inputs and have output connections to other spinal interneurones and to other Renshaw cells. So recurrent inhibition is more than just negative feedback from and to motoneurones and may have several functions depending upon motor context. Lamy et al. have focused on heteronymous actions (which are more widespread in man than in cats or monkeys) in the context of our unique bipedal form of walking. The knee extensor quadriceps is a source of recurrent inhibition to the ankle extensor and the flexor muscles soleus and tibialis anterior. But given that these ankle muscles are antagonists, how is differential activation achieved? The authors found that around heel strike and early in stance, when quadriceps is active and soleus activity is increasing, recurrent inhibition of soleus is weak. Conversely, later in stance, when quadriceps is active and soleus activity is declining, recurrent inhibition of soleus is strong. Recurrent inhibition of tibialis anterior motoneurones was neither task nor phase dependent. The reduction in soleus recurrent inhibition would assist the transition from swing to stance and enhanced inhibition later in stance would favour the transition from stance to swing by reducing reciprocal inhibition of tibialis anterior. The origin of these changes in recurrent inhibition remains uncertain but activity of peripheral sensory or descending motor pathways could be involved. Two interesting possibilities are the corticospinal pathway, known to depress homonymous recurrent inhibition of soleus in sitting subjects (Mazzocchio et al. 1994) and the vestibulospinal pathway that depresses recurrent inhibition of soleus in standing stance (Iles & Pisini, 1992). It might be possible to extend such studies to heteronymous actions in walking stance. More meticulous experiments built upon the framework of human research protocols pioneered by the Paris group will likely increase our understanding of recurrent inhibition even further.

Modulation of recurrent inhibition from knee extensors to ankle motoneurones during human walking

The neural control for muscle coordination during human locomotion involves spinal and supraspinal networks, but little is known about the exact mechanisms implicated. The present study focused on modulation of heteronymous recurrent inhibition from knee extensors to ankle motoneurones at different times in the gait cycle, when quadriceps (Quad) muscle activity overlaps that in tibialis anterior (TA) and soleus (Sol). The effects of femoral nerve stimulation on ankle motoneurones were investigated during treadmill walking and during tonic co-contraction of Quad and TA/Sol while standing. Recurrent inhibition of TA motoneurones depended on the level of background EMG, and was similar during walking and standing for matched background EMG levels. On the other hand, recurrent inhibition in Sol was reduced in early stance, with respect to standing, and enhanced in late stance. Reduced inhibition in Sol was also observed when Quad was coactivated with TA around the time of heel contact, compared to standing at matched background EMG levels in the two muscles. The modulation of recurrent inhibition of Sol during walking might reflect central and/or peripheral control of the Renshaw cells. These modulations could be implicated in the transition phases, from swing to stance to assist Sol activation during the stance phase, and from stance to swing, for its deactivation.

Early alterations in the electrophysiological properties of rat spinal motoneurones following neonatal axotomy.

Early in development, motoneurones are critically dependent on their target muscles for survival and differentiation. Previous studies have shown that neonatal axotomy causes massive motoneurone death and abnormal function in the surviving motoneurones. We have investigated the electrophysiological and morphological properties of motoneurones innervating the flexor tibialis anterior (TA) muscle during the first week after a neonatal axotomy, at a time when the motoneurones would be either in the process of degeneration or attempting to reinnervate their target muscles. We found that a large number (∼75%) of TA motoneurones died within 3 weeks after neonatal axotomy. Intracellular recordings revealed a marked increase in motoneurone excitability, as indicated by changes in passive and active membrane electrical properties. These changes were associated with a shift in the motoneurone firing pattern from a predominantly phasic pattern to a tonic pattern. Morphologically, the dendritic tree of the physiologically characterized axotomized cells was significantly reduced compared with age-matched normal motoneurones. These data demonstrate that motoneurone electrical properties are profoundly altered shortly after neonatal axotomy. In a subpopulation of the axotomized cells, abnormally high motoneurone excitability (input resistance significantly higher compared with control cells) was associated with a severe truncation of the dendritic arbor, suggesting that this excitability may represent an early electrophysiological correlate of motoneurone degeneration.