Presynaptic Inhibition Of Ia Fibres Research Articles

Quantitative input-output relationships between human soleus muscle spindle afferents and motoneurons

A method is described that, for the first time, allows instantaneous estimation of the Ia fiber input to human soleus motoneurons following electrical stimulation of the tibial nerve. The basis of the method is to determine the thresholds of the most and least excitable 1a fibers to electrical stimulation, and to treat the intervening thresholds as having a normal distribution about the mean; the validity of this approach is discussed. It was found that, for the same Ia fiber input, the percentage of soleus motoneurons contributing to the H (Hoffmann)-reflex differed considerably among subjects; when the results were pooled, however, there was an approximately linear relationship between Ia input and motoneuron output. Weak extension of the great toe diminished the soleus motoneuron reflex discharge in all but 2 of 16 subjects; the results for weak ankle plantarflexion were less consistent, but overall, there was a reduction in soleus motoneuron output also. The methodology should provide new insights into disorders of movement and tone, especially as it permits estimates of motoneuron depolarization to be made. NEW & NOTEWORTHY Assuming a normal distribution of Ia fiber thresholds to electrical stimulation and using the H-reflex, we determined for the first time an Ia input-α-motoneuron output relationship for the human soleus muscle. The relationship varies greatly among subjects but, overall, is approximately linear. Minimal contraction of a toe muscle alters the relationship dramatically, probably due to presynaptic inhibition of Ia fibers. Drawing on the literature, we can calculate changes in α-motoneuron membrane potential.

Ethanol reduces motoneuronal excitability and increases presynaptic inhibition of Ia afferents in the human spinal cord

Introduction: Already low blood concentrations of ethanol acutely impair motor control and coordination. In vitro experiments have given evidence that spinal effects of ethanol contribute to this by reducing spinal excitability and enhancing presynaptic inhibition of Ia fibers. In this study, we investigated the influence of 0.7 g per kilogram of bodyweight ethanol on motoneuronal excitability and presynaptic inhibition in humans. Methods: The study was performed in 10 volunteers. Spinal excitability was measured by the maximal H-reflex of the soleus muscle normalized to the maximal muscular response (Hmax/Mmax). Presynaptic inhibition was measured by changes in heteronymous Ia-facilitation of the soleus H-reflex, which is achieved by stimulation of the femoral nerve. A decrease in facilitation can be ascribed to an increase in presynaptic inhibition. Changes of these parameters under the influence of 0.7 g per kilogram of bodyweight ethanol were assessed in comparison to control measurements before ethanol application. Results: Both parameters, Hmax/Mmax and Heteronymous facilitation, were significantly reduced under the influence of ethanol (Wilcoxon signed-rank test with Bonferroni correction for each, p < 0.01). Discussion: The increase in presynaptic inhibition by ethanol is probably caused by an increase in GABA A receptor-mediated Cl-conductance, which has been shown in spinal cord cultures. The role of presynaptic inhibition in movement is assumed to be there to control the afferent input of muscle spindles and tendon organs as a mechanism of specific input-selection. This study demonstrated that ethanol reduces spinal excitability and increases GABAergic presynaptic inhibition on Ia afferent fibers in humans.

Impaired EMG inhibition elicited by tendon stimulation in dystonia.

to test the effects of tendon stimulation on isometric voluntary contraction. Twenty patients with dystonia (12 patients with generalized and eight with task-specific dystonia) and 10 normal healthy subjects participated in the study. The tendon of the extensor carpi radialis muscle was stimulated with electrical stimuli at the wrist, and the electromyogram (EMG) signal was recorded during an isometric voluntary contraction. In normal subjects, tendon stimulation elicited an excitatory phase (TE1), followed by a pronounced inhibitory phase (TI1) and a second excitatory phase (TE2). The three phases had similar perceptive thresholds, latencies, and durations in patients and control subjects. In patients with generalized dystonia, the TI1 area exceeded the control values (controls [mean +/- SE], 40.3 +/- 5.4; patients, 66.9 +/- 5.5; p = 0.0048, Mann-Whitney U: test). In the patients with task-specific dystonia, the TI1 area was similar to control values (controls [mean +/- SE], 40.3 +/- 5.4; patients, 54.2 +/- 4.8; p = 0.7396, Mann-Whitney U: test). The EMG suppression (TI1) after tendon stimulation is reduced in generalized dystonia, indicating a decreased group III-elicited presynaptic inhibition of Ia fibers. The impaired group III presynaptic inhibitory action from tendon afferents could contribute to the motor abnormalities present in dystonia. Dystonia causes widespread dysfunction of presynaptic inhibitory mechanisms in the spinal cord, involving Group I and III afferents.

Presynaptic excitability changes of group Ia fibres to muscle nociceptive stimulation in humans

Tonic muscle nociceptive discharge evoked chemically from the foot extensor digitorum brevis muscle in man produces a depression of Ia excitation and Ib inhibition of the soleus (Sol) motoneurones (Mns). The possibility that both these changes partly result from presynaptic inhibition of Ia fibres projecting to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is tested. Convergence of Ia fibres on these interneurones was deduced from evidence that reducing the excitatory effect of the extensor Ia fibres (by potentiation of their presynaptic inhibition) resulted in Ib disinhibition. Nociceptive-induced potentiation of Ia presynaptic inhibition was deduced from the following congruent results obtained by two independent methods: (1) depression of heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns; (2) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical activation of the tibialis anterior primary spindle afferents. It is concluded that nociceptive volleys arising from dorsal foot muscles facilitate the activity of interneurones intercalated in pathways responsible for presynaptic inhibition of Sol Ia fibres. It is also proposed that the same Ia presynaptic inhibition depresses the excitability of interneurones mediating group I non-reciprocal inhibition, thus resulting in Ib disinhibition of Sol Mns.

Electrical stimulation over muscle tendons in humans. Evidence favouring presynaptic inhibition of Ia fibres due to the activation of group III tendon afferents.

Electrical stimulation over muscle tendons produces a transient suppression of voluntary EMG activity; its onset latency is approximately 55 ms in the forearm extensor muscles. This phenomenon has been attributed to the activation of a polysynaptic inhibitory pathway originating from Ib afferent fibres. To clarify its origin we conducted several experiments in 10 normal healthy subjects. The EMG silence after tendon stimulation appeared at relatively high stimulus intensities (> 50 mA); conditioning cutaneous stimulation left it unchanged, and the inhibition had a short recovery cycle (50 ms). Tendon stimulation still evoked EMG suppression during an ischaemic block of fast-conducting afferents. The motor potentials evoked by transcranial magnetic stimulation of the motor cortex during the EMG silence remained almost unchanged, whereas the H reflex was strongly inhibited. Hence we conclude that tendon stimulation activates slow-conducting tendon afferents, possibly group III fibres, connected not through a polysynaptic pathway originating from Ib afferents but through an oligo- or disynaptic inhibitory circuit. The EMG suppression after tendon stimulation probably represents a dysfacilitation of the alpha-motor neurons due to presynaptic inhibition of Ia fibres produced by tendon afferent input to the spinal cord.

Inhibitory effects on flexor reflexes in patients with a complete spinal cord lesion.

The inhibitory effects on flexors of electrical stimulation of a distal peripheral nerve were investigated in 7 paraplegic patients having a complete spinal cord section. The stimuli (3-50 mA) were applied to the sural nerve. Their effects were investigated on: 1) the ipsi- and contralateral H reflex of the Tibialis Anterior (TA); 2) the continuous EMG activity reflexly elicited in TA by a sustained pinch of the foot and 3) on the reflexes evoked in TA by contralateral sural nerve stimulation. Sural nerve stimulation induced two peaks of facilitation of the ipsilateral TA H reflex that could be replaced by inhibition as the stimulus intensity was increased. The comparison of the effect on H reflexes and the EMG activity suggests presynaptic inhibition of Ia fibres at time intervals longer than 300 ms. The stimulation could depress the sustained EMG reflex activity and induce a period of silence whose duration increased with the intensity of the stimulation. As shown in a previous study, a sural nerve stimulation induced a reflex in TA with a prolonged (more than 130 ms) latency. This late reflex could be selectively inhibited by a contralateral sural nerve stimulation, probably at an interneuronal level. These results confirm that the late reflex in TA is similar to the one observed after Flexor Reflex Afferent (FRA) stimulation in the acute spinal cat with DOPA. In addition, they show that at least some part of the "half centre" organization which has been described in the acute spinal cat with DOPA is also present in the human spinal cord chronically deprived of supraspinal control.

Effects of stimulation of group I afferents from flexor muscles on heterosynaptic facilitation of monosynaptic reflexes produced by Ia and descending inputs: a test for presynaptic inhibition

1. In the chloralose anesthetized cat, conditioning stimulation of group I flexor afferents depresses the monosynaptic potentials generated by Ia afferents in single spinal motoneurons or in populations of motoneurons without affecting the monosynaptic potentials produced by stimulation of descending fibers in the ipsilateral ventromedial fasciculus (VMF). 2. Heterosynaptic facilitation of monosynaptic reflexes was used to test changes in the presynaptic effectiveness of excitatory inputs with direct connections with motoneurons. We found that the heterosynaptic facilitation of Ia origin was reduced by conditioning stimulation of group I afferents from flexors, without affecting the heterosynaptic facilitation produced by stimulation of the VMF. 3. These results confirm and expand previous observations showing that the synaptic effectiveness of descending fibers synapsing with motoneurons is not subjected to a presynaptic control mechanism of the type acting on Ia fiber terminals, and provide further basis for the use of changes in heterosynaptic facilitation of monosynaptic reflexes of Ia origin as an estimate of changes in presynaptic inhibition of Ia fibers (Hultborn et al. 1987a).

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.

Changes in presynaptic inhibition of Ia fibres to soleus motoneurones during voluntary dorsiflexion of the foot.

Variations of presynaptic inhibition in heteronymous Ia fibres projecting to soleus motoneurones were studied during the first 250 ms of phasic voluntary isometric contractions of the antagonist tibialis anterior muscle in human subjects. During the first 60-80 ms of TA e.m.g activity, presynaptic inhibition was often more marked than at rest, but not in all experimental sessions. After 60-80 ms, presynaptic inhibition was always increased compared to rest and to the onset of TA e.m.g. activity. A "rebound" in femoral nerve induced Ia facilitation was often observed between 90-150 ms. The early increase in presynaptic inhibition was widespread and non specific since it was observed at the onset of extensor carpi radialis contractions of maximal strength. The "rebound" in heteronymous Ia facilitation was interpreted as a relative decrease in presynaptic inhibition to which nonspecific suprasegmental and cutaneous effects contributed. The late increase in presynaptic inhibition in Ia fibers to soleus motoneurones was considered as reciprocally inhibiting the Sol H-reflex, thus counteracting the phasic stretch of the antagonist muscle during TA contraction.

Changes in presynaptic inhibition of Ia fibres in man while standing.

Presynaptic inhibition of homonymous Ia afferent terminals to soleus, quadriceps and tibialis anterior motoneurons and of heteronymous Ia fibres from quadriceps to soleus was compared in the same subjects when standing without support and during a control situation (sitting or standing with back support). Changes in presynaptic inhibition of Ia fibres were indirectly deduced from alterations in the amount of monosynaptic Ia facilitation elicited in motoneurons by a constant conditioning stimulation. Facilitation was measured during the first 0.5 ms when the monosynaptic Ia excitatory postsynaptic potential (EPSP) was not yet contaminated by polysynaptic effects evoked by the conditioning stimulation. Two indirect methods were used to provide an estimate of the size of the conditioning Ia EPSP: (1) the resulting H reflex facilitation; and (2) the peak of increased firing probability elicited in voluntarily activated motoneurons by stimulation of homonymous and heteronymous Ia fibres (poststimulus time histogram PSTH method). Only those PSTH experiments in which the 'spontaneous' firing rate of the motor unit was identical in the different positions, thus ensuring an identical net synaptic drive to the motoneuron, were considered. Under these conditions it is assumed that changes in the size of the peak of facilitation elicited by the monosynaptic Ia volley are likely to be caused by changes in presynaptic inhibition of Ia fibres. It is argued that the substantial changes in monosynaptic Ia excitation observed when standing without support probably reflect changes in presynaptic inhibition of Ia fibres. Under this interpretation, presynaptic inhibition of Ia fibres to soleus motoneurons is increased while standing without support, whereas presynaptic inhibition of homonymous Ia fibres to quadriceps motoneurons is decreased. There is no evidence for a change in presynaptic inhibition of Ia fibres to tibialis anterior motoneurons. The resulting alterations in the gain of the monosynaptic reflex of these muscles are discussed in relation to the possible role of the monosynaptic stretch reflex in human gait.

Changes in presynaptic inhibition of Ia fibres at the onset of voluntary contraction in man.

1. Two independent methods were used, in man, to assess changes in presynaptic inhibition of I a terminals at the onset of selective voluntary contractions: (1) measurement of the amount of heteronymous monosynaptic I a facilitation (from the quadriceps muscle to soleus motoneurones) to provide an assessment of the amount of ongoing presynaptic inhibition exerted on the I a fibres responsible for the facilitation; (2) measurement of the inhibition of H reflexes 40-60 ms after a short vibration to the tibialis anterior tendon to estimate the excitability of the interneurones mediating presynaptic inhibition from tibialis anterior I a afferents to the I a afferents of the test H reflex (soleus or quadriceps). 2. At the onset of an isolated voluntary plantar flexion of the foot (gastrocnemius-soleus contraction) the heteronymous facilitation from quadriceps to soleus was increased, reflecting a decreased presynaptic inhibition of the quadriceps I a terminals on soleus motoneurones. Vibratory inhibition of the soleus H reflex was decreased, reflecting an inhibition of transmission of presynaptic inhibition to homonymous soleus I a afferent terminals. 3. At the onset of the same gastrocnemius-soleus contraction there was, on the contrary, an increased vibratory inhibition of the quadriceps H reflex indicating a facilitation of transmission of presynaptic inhibition to homonymous quadriceps I a afferent terminals. 4. At the onset of an isolated voluntary knee extension (quadriceps contraction) the opposite pattern was seen: the heteronymous facilitation from quadriceps to soleus was decreased and the vibratory inhibition of a soleus H reflex was increased, whereas the vibratory inhibition of the quadriceps H reflex was decreased. 5. These results indicate that presynaptic inhibition of I a afferent terminals on motoneurones of contracting muscles is decreased, permitting I a activity to contribute to excitation of voluntarily activated motoneurones. On the contrary, presynaptic inhibition of I a fibres to motoneurones of muscles not involved in the contraction is increased. It is argued that the former must be supraspinal in origin. 6. It is concluded that the control of presynaptic inhibition of I a fibres at the onset of movement may be organized so as to aid in achieving selectivity of muscle activation, i.e. so as to increase motor contrast.

Changes in segmental reflexes following chronic spinal cord hemisection in the cat. II. Conditioned monosynaptic test reflexes.

In a companion paper (Hultborn & Malmsten 1983) it was described that ventral root discharges to stimulation of peripheral nerves became larger on the side of a chronic spinal hemisection (left) than on the other side. In the present paper, based on the same experiments, conditioning of monosynaptic test reflexes was used to study changes of both excitatory and inhibitory effects on specified motoneuronal pools. Conditioning stimulation was given to IA afferents (reciprocal Ia inhibition, presynaptic inhibition of Ia fibers), high threshold muscle afferents, low and high threshold cutaneous afferents and motor axons (recurrent inhibition). A comparison of the efficacy of conditioning stimuli on the two sides showed that facilitatory effects were larger on the side of hemisection in a clear majority of cases. Inhibition was almost always either more efficient on the side of hemisection or equally efficient on the two sides. In control cats, facilitatory effects tended to be larger on the right side, while the results for inhibitory conditioning generally showed no clear side-bias. The increase in facilitatory effects after lesions may contribute to symptoms of spasticity.

Effect of stretching the patella tendon on voluntary and reflex contractions of the calf muscles in man

In nine subjects the calf muscles were made to contract either voluntarily or by eliciting a Hoffmann reflex. The patella tendon was stretched during voluntary contractions or at short time intervals before a Hoffmann reflex. Stretching the patella tendon produced inhibition of different duration on the two types of contraction. Inhibition after a tap to the patella tendon lasted 20 to 30 ms during voluntary contraction of the calf muscles and usually for more than 100 ms when preceding a reflex contraction. The preferred interpretation of this phenomenon is that during voluntary contraction presynaptic inhibition of Ia fibers from the calf muscles after stimulation of probably Golgi tendon organs in quadriceps femoris is reduced or switched off. Thus, during reflex contraction, the long inhibitory time course is due to presynaptic inhibition, whereas during voluntary contraction postsynaptic inhibition determines the inhibitory time course. In two subjects, specifically investigated on the point, the tap to the patella tendon facilitated the simultaneously elicited Hoffmann reflex.