Presynaptic Inhibition Of Ia Terminals Research Articles

Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling.

Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation (CONTROL + STIM), sprints with sensory stimulation (SPRINT + STIM) and sprints without stimulation (SPRINT). Seven participants also performed a fourth session (CONTROL), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM, participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM, participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared to sprints without stimulation. These results demonstrate that sensory stimulation can substantially mitigate the fatiguing effects of sprints.

Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats

Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L(7) ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.

Paired Associative Stimulation Induces Change in Presynaptic Inhibition of Ia Terminals in Wrist Flexors in Humans

Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1 and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.

Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb

Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI <100 ms) resembling the inhibition seen in the voluntary EMG. This was consistent with the postsynaptic origin of cutaneous inhibition of the motoneurons.

The disynaptic group I inhibition between wrist flexor and extensor muscles revisited in humans

The present studies are designed to further characterise the interneuronal pathway mediating the disynaptic reciprocal group I inhibition between flexors and extensors at the wrist and the elbow levels in humans. In the first series of experiments, we compared the electrical threshold of the reciprocal group I inhibition at the wrist and the elbow level after a prolonged vibration aimed at raising the electrical threshold of the antagonistic activated Ia afferents. Prolonged vibration to the 'conditioning' tendon, which raised significantly the electrical threshold of the inhibition at the elbow level, did not alter it at the wrist level. These results suggest that the dominant input to the relevant interneurones is Ia in origin at the elbow level but Ib in origin at the wrist level. In the second series of experiments, using the spatial facilitation method, we compared the effects on the post-stimulus time histograms of single voluntarily activated motor units of two volleys delivered both separately and together to group I afferents in the nerves supplying the homonymous and antagonistic muscles. At the wrist, but not at the elbow level, the peak of homonymous monosynaptic group I excitation was reduced on combined stimulation, although the antagonistic IPSP was just at the threshold. Because the suppression did not involve the initial bins of the peak, it is argued that the suppression is not due to presynaptic inhibition of Ia terminals, but probably reflects convergence between the homonymous and antagonistic volleys onto the interneurones mediating the disynaptic inhibition. Taken together with the previously reported effects of recurrent inhibition on reciprocal inhibition, these results suggest that inhibition between flexors and extensors is differently organised at the elbow (reciprocal Ia inhibition) and the wrist (non-reciprocal group I inhibition) levels. It is argued that the particular connectivity at the wrist level might correspond to some functional requirements at this ball joint.

Suppression of the H reflex in humans by disynaptic autogenetic inhibitory pathways activated by the test volley.

The present studies were designed to increase an existing limitation on the size of the H reflex by accentuating an inhibitory effect of group I afferents in the test volley. They were precipitated by the observation that, during strong voluntary contractions of quadriceps (Q), the late deep peroneal (DP) facilitation of the Q H reflex was suppressed but the facilitation of the ongoing EMG was not. The effects of conditioning stimuli to DP, superficial peroneal (SP) and articular afferents on the excitation of Q motoneurones (MNs) produced by femoral nerve (FN) stimulation were assessed in 11 healthy human subjects using the H reflex of vastus intermedius or the peak of group I excitation in post-stimulus time histograms (PSTHs) of single motor units (MUs) in vastus lateralis. The suppression of the late H reflex facilitation was observed during strong contractions after stimulation of DP and articular afferents, and at rest when DP and SP volleys were combined. In all single MUs tested, the FN-induced peak of excitation was suppressed by DP stimulation during strong Q contractions and by a combination of conditioning volleys (SP with DP or articular) during weak contractions. By themselves these conditioning volleys did not inhibit the background MU discharge even when delivered together. The suppression did not involve the initial bins of the peak; it began 0.7 ms later than the probable onset of monosynaptic Ia facilitation. It is argued that the suppression is not due to presynaptic inhibition of Ia terminals or to recurrent inhibition, but probably reflects convergence between the conditioning volleys and group I afferents in the test FN volley onto interneurones of the disynaptic non-reciprocal group I inhibition. It is concluded that the size of the H reflex is limited by disynaptic inhibition, and that changes in the excitability of this inhibitory pathway can produce prominent changes in the H reflex.

Neuromuscular changes after long-lasting mechanically and electrically elicited fatigue.

Central fatigue was investigated under an isolated active condition whereby the possible effects of supraspinal fatigue were minimized. Therefore, ten subjects were fatigued by simultaneously and repeatedly mechanically stretching and electrically stimulating their calf muscles for 1 h. This was performed using an ankle ergometer. The active fatigue task included a total of 2400 muscle stretches with an intensity of 10% of the maximal voluntary contraction (MVC). This protocol clearly impaired neuromuscular function, as revealed by a significant reduction in MVC (P < 0.01) and the neural input to the muscle (average EMG) (P < 0.01-0.001). The interpolated nerve stimulation compensated for this force loss by 4.28% (P < 0.05). Stretch-reflex recordings revealed a notable post-fatigue reduction in the peak-to-peak amplitude (59.1%, P < 0.01) and stretch-resisting force of the muscle (14.1%, P < 0.01). The maximal H-reflex declined by 50.5% (P < 0.001) and did not recover while the leg was kept ischemic. It is suggested that the existing protocol with minor metabolic loading can induce central fatigue, which seems to be of reflex origin from the fatigued muscle. Although the role of presynaptic inhibition of Ia terminals is possibly reinforced, disfacilitation via reduced spindle sensitivity cannot be excluded.

Modulation of presynaptic inhibition of la afferents during voluntary wrist flexion and extension in man.

Changes in presynaptic inhibition of Ia terminals directed to flexor carpi radialis (FCR) motoneurones (MNs) were investigated in normal human subjects at rest and during voluntary wrist flexion and extension. To that end, two independent methods were used: (1) the radial-induced D1 inhibition of the FCR H reflex, which assesses the excitability of PAD (primary afferent depolarisation) interneurones controlling presynaptic inhibition of Ia terminals mediating the afferent volley of the FCR H reflex; and (2) the heteronymous monosynaptic Ia facilitation induced in the FCR H reflex by intrinsic muscle Ia afferent stimulation, which assesses the ongoing presynaptic inhibition of Ia terminals. With respect to results at rest, it was found that at the onset of (and during tonic) voluntary wrist flexion, D1 inhibition was reduced and heteronymous monosynaptic Ia facilitation was increased. This suggests that, as in the lower limb, presynaptic inhibition is decreased on Ia terminals projecting to MNs involved in the voluntary contraction. In contrast with results observed in the lower limb, presynaptic inhibition of Ia terminals to FCR MNs was also found to be reduced at the onset of a voluntary contraction involving the antagonistic wrist extensors, suggesting that presynaptic inhibition of Ia terminals projecting to wrist flexors and extensors might be mediated through the same subsets of PAD interneurones. This is in keeping with other features showing that the organisation of reflex pathways between wrist flexors and extensors differs from that observed at other (elbow, ankle) joints.

Distribution of non-monosynaptic excitation to early and late recruited units in human forearm muscles.

The distribution of monosynaptic and nonmonosynaptic excitation was investigated within flexor carpi radialis (FCR) and extensor carpi radialis (ECR) motoneurone (MN) pools. FCR H reflexes of different size were conditioned by various conditioning stimuli eliciting different effects: (1) musculocutaneous-induced non-monosynaptic excitation of FCR MNs at the onset of biceps contraction, (2) heteronymous monosynaptic Ia facilitation, (3) reciprocal Ia inhibition, and (4) presynaptic inhibition of Ia terminals. Musculocutaneous-induced non-monosynaptic excitation increased continuously with the size of the unconditioned reflex. In contrast, heteronymous monosynaptic Ia excitation first increased and then decreased, with increases in the unconditioned reflex size, reciprocal inhibition and presynaptic inhibition showing an approximately similar tendency. This suggests that the non-monosynaptic excitation is distributed more evenly to early and late recruited MNs than monosynaptic Ia excitation, reciprocal inhibition and presynaptic inhibition. A different pattern of homonymous radial-induced monosynaptic and non-monosynaptic excitation was also found for individual ECR MNs investigated with the poststimulus time histogram (PSTH) method. Whereas the monosynaptic Ia excitation tended to be most marked in lower threshold MUs, the nonmonosynaptic excitation was evenly distributed to lower and higher threshold MUs. We propose that the even distribution of the non-monosynaptic excitation in the motoneuronal pool may be of significance when it is necessary to activate a wide range of MNs more or less simultaneously.

Presynaptic inhibition and homosynaptic depression: A comparison between lower and upper limbs in normal human subjects and patients with hemiplegia

Presynaptic inhibition of Ia terminals and postactivation depression at the Ia fibre-motor neuron (MN) synapses were compared in the upper and lower limbs of both sides in subjects from different populations: 49 spastic patients with hemiplegia [mainly with a lesion in the middle cerebral artery (MCA) area], two tetraplegics and 35 healthy subjects. Presynaptic inhibition was assessed using D1 inhibition of the soleus and the flexor carpi radialis (FCR) H reflexes elicited by electrical stimuli applied to the nerve supplying antagonistic muscles, and postactivation depression was explored by varying the time interval between two consecutive H reflexes. In normal subjects no right-left asymmetry was found in the amount of presynaptic Ia inhibition, homosynaptic depression or the H(max)/M(max) ratio. In the hemiplegic side of patients with MCA area lesions, the H(max)/M(max) ratio was significantly increased in the soleus but not in the FCR. Presynaptic inhibition of Ia terminals, which was significantly reduced at the cervical level on the hemiplegic side (and also, but to a lesser extent, on the unaffected side), was unchanged at the lumbar level. Homosynaptic depression was similarly reduced at the cervical and lumbar levels on the hemiplegic side but not modified on the unaffected side. It is argued that the decrease in presynaptic inhibition of Ia terminals is more a correlate of spasticity than a mechanism underlying it. The decrease in postactivation depression, which very probably contributes to the exaggeration of the stretch reflex characterizing spasticity, might be a consequence of the changes in the pattern of activation of Ia afferents and MNs following the motor impairment.

The monosynaptic reflex: a tool to investigate motor control in humans. Interest and limits

The principle of the monosynaptic reflex used as a tool to explore the excitability of the motoneurones (MNs) is explained and the general methodology of the H reflex is described. The different drawbacks inherent in the technique are then considered: mechanisms other than the monosynaptic Ia excitation of MNs contributing to the H reflex size (limitation of the H reflex size by disynaptic IPSPs, presynaptic inhibition of Ia terminals, post-activation depression); non-linearity and changes in the `recruitment gain' in the MN pool; and poor time resolution of the method. Despite these drawbacks, it is emphasized that the H reflex is the only available technique enabling one to investigate changes in transmission in spinal pathways during motor tasks.

Modulation of the biceps femoris tendon jerk reflex during human locomotion.

During gait it is generally accepted that there is a reduction in amplitude of H-reflexes as compared to standing. For short-latency stretch reflexes, however, it is less clear whether a similar reduction in reflex gain is present during locomotion. Stretches of constant amplitude are hard to produce under these circumstances and for this reason some previous studies on the biceps femoris (BF) have used "reduced gait" in which the stimulated leg is stepping on the spot while the contralateral leg is walking on a treadmill. With this method it was possible to show that BF tendon jerk reflexes are larger at end swing and therefore are likely to contribute to the EMG burst normally occurring in that part of the step cycle when the BF is rapidly stretched. In the present study two questions were addressed: first, whether the reflex is different in size during gait compared to standing and, second, whether it is modulated in size during the gait cycle not only during reduced but also during normal gait. It was found that during both types of gait there was a general reflex depression with regard to the respective control values obtained during standing at similar EMG activity levels. In previous studies on soleus and quadriceps, discrepancies between EMG activity and reflex amplitude have been ascribed to changes in presynaptic inhibition of Ia terminals mediating the afferent volley of the reflex. Based on the data presented, this may also be true for the BF. In both normal and reduced gait the reflex was similarly modulated in size, showing a maximum at the end of swing. This similarity implies that reduced gait may be useful as an acceptable alternative for normal gait in studies on phase-dependent reflex modulation during locomotion.

Assessing changes in presynaptic inhibition of Ia afferents during movement in humans

Different methods, based on different principles, have been proposed to estimate changes in presynaptic inhibition of Ia terminals (accompanied by primary afferent depolarization, (PAD)) during voluntary contraction in humans. (i) A discrepancy between the H-reflex amplitude, at an equal level of EMG activity, in two situations (e.g., walking and standing) may be taken as suggesting a different control of PAD interneurones in the two cases. (ii) A conditioning stimulation (vibration or electrical stimulation) is used to activate PAD interneurones and to evoke presynaptic inhibition of the afferent volley of the test reflex. The resulting long-lasting depression of the reflex depends on the excitability of PAD interneurones, but can be contaminated by long-lasting post-synaptic effects. (iii) The amount of reflex facilitation evoked by a purely monosynaptic Ia volley varies inversely with the on-going presynaptic inhibition of Ia afferents mediating the conditioning volley, and can be used to assess this on-going presynaptic inhibition. None of these methods can provide by itself unequivocal evidence for a change in presynaptic inhibition of Ia terminals, but reasonably reliable interpretations may be proposed when congruent results are obtained with different methods. Thus it has been shown that, during selective voluntary contraction, presynaptic inhibition is decreased on Ia afferents projecting on motoneurones of the contracting muscle and increased on Ia afferents projecting on motor nuclei not involved in the contraction.

Modulation, probably presynaptic in origin, of monosynaptic Ia excitation during human gait.

Modulation of presynaptic inhibition of Ia afferents projecting monosynaptically to soleus motoneurones was investigated during human gait. Changes in presynaptic inhibition of Ia afferents were deduced from alterations in the amount of heteronymous soleus H-reflex facilitation evoked by a constant femoral nerve stimulation. It has been shown that this facilitation is mediated through a monosynaptic Ia pathway and that during its first 0.5 ms it is still uncontaminated by any polysynaptic effect and can be used to assess ongoing presynaptic inhibition of Ia terminals to soleus motoneurones. During gait, heteronymous facilitation was reduced with respect to its control value (rest during sitting) and modulated during the step cycle: it reached its maximum at mid-stance and decreased to near zero by the end of stance. At the same time the H-reflex amplitude was to some extent similarly modulated. It is argued that this decrease in heteronymous Ia facilitation and in H-reflex amplitude reflects an increased, ongoing presynaptic inhibition of Ia terminals projecting onto soleus motoneurones, which could be from central and/or peripheral origin. D1 inhibition, i.e. the late and long-lasting inhibition of the soleus H-reflex evoked by a train of stimuli to the common peroneal nerve, was used as another method to assess presynaptic inhibition. This D1 inhibition was decreased during gait, and it is argued that this decrease might reflect an occlusion in presynaptic pathways or increased presynaptic inhibition of pathways mediating the conditioning volley.

A quantitative assessment of presynaptic inhibition of Ia afferents in spastics. Differences in hemiplegics and paraplegics.

Soleus H-reflex facilitation evoked by a supramaximal conditioning stimulation to the femoral nerve was investigated in 28 healthy control subjects and 35 spastic patients of whom 17 were paraplegics with bilateral spinal cord lesion and 18 were hemiplegics with unilateral cerebral lesion. Heteronymous facilitation from quadriceps to soleus was measured 0.4 ms after onset, while the monosynaptic Ia excitation is still uncontaminated by any non-monosynaptic effect and can be used to assess ongoing presynaptic inhibition on Ia terminals to soleus motor neurons. In paralegics, this heteronymous Ia facilitation was significantly larger than in control subjects (all individual results in these patients being above the mean observed in controls). This must reflect a decrease in presynaptic inhibition of Ia terminals in the paraplegics explored here. There was no correlation between this decreased presynaptic inhibition of Ia terminals and the degree of spasticity measured by Ashworth's scale. Surprisingly, the amount of heteronymous Ia facilitation in hemiplegics was the same as in normal subjects. This indicates that presynaptic inhibition of Ia terminals is unchanged in these patients and disagrees with the usual interpretation of reduced vibratory inhibition of the soleus H-reflex in hemiplegics. It is argued that this disagreement is due to the fact that vibratory inhibition of the reflex also depends on post-activation depression following repetitive synaptic transmission.

Gating of the afferent volley of the monosynaptic stretch reflex during movement in man.

1. The time course of the changes in presynaptic inhibition of Ia fibres to soleus motoneurones has been investigated during a voluntary ramp-and-hold plantar flexion. 2. Monosynaptic Ia facilitation of the soleus H reflex was evoked by stimulation of the inferior soleus (homonymous) and femoral (heteronymous) nerves. Changes in presynaptic inhibition of the Ia fibres mediating the conditioning volleys were inferred from changes in the amount of reflex facilitation evoked by such constant conditioning stimulations. 3. At the beginning of the voluntary contraction, both homonymous and heteronymous Ia facilitations were markedly increased with respect to their rest values. Then, they dropped abruptly in the middle of the ramp, whatever the ramp duration. 4. The stronger the contraction at the end of the ramp, the larger the initial increase in reflex facilitation. 5. These results indicate that presynaptic inhibition of Ia terminals on motoneurones of the contracting muscle is decreased during the first half of the ramp and then returns to its rest level. It is argued that these changes in presynaptic inhibition are centrally programmed, and it is suggested that, under certain conditions, presynaptic inhibition can be modulated according to both the strength and timing of the contraction. 6. The functional role of the resulting changes in the gain of the stretch reflex is discussed.

Ia afferents of the antagonist are inhibited presynaptically before the onset of a ballistic muscle contraction in man.

The aim of the present investigation was to study whether the pre-movement inhibition of the H reflex in the antagonist of a ballistic voluntary contraction was due to a reduced activity of the motoneuronal pool of the antagonist, or to a reduced excitatory effect of the afferent volley reaching these motoneurons. Human subjects performed visually conditioned ballistic dorsal flexions of the ankle. The inhibition of the H reflex in the antagonist (soleus muscle) was similar if the muscle was initially relaxed or if there was a preexisting level of motor discharge. Since the soleus muscle was inhibited before movement onset in parallel with the H reflex inhibition, the relation between the level of a background activity and the size of superimposed H reflexes was studied. The finding that H reflexes were only slightly reduced in size with decreasing steady EMG levels could not explain the pre-movement inhibition, and it was concluded than an increased presynaptic inhibition of Ia terminals was the source of the H reflex inhibition.

Reciprocal group I inhibition on triceps surae motoneurons in man.

Reciprocal group I inhibition on triceps surae motoneurons in man.

Excitability and inhibitability of motoneurons of different sizes.

Excitability and inhibitability of motoneurons of different sizes.