Cortical control of presynaptic inhibition of Ia afferents in humans

The effect of transcranial magnetic stimulation was investigated on presynaptic inhibition of Ia terminals in the human upper and lower limb. Presynaptic inhibition of Ia afferents was assessed by three different and independent methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing presynaptic inhibition of Ia afferents in the conditioning volley); (2) long-lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing presynaptic inhibition on Ia afferents in the test volley); (3) measurement of the monosynaptic Ia peak evoked in single motor units by a homonymous or heteronymous volley (post stimulus time histogram method). The first two methods were used on the lower limb; the last two on the upper limb. Provided that the corticospinal volley and the explored Ia volley were directed to the same target motoneurones, cortical stimulation evoked significant and congruent changes: (1) In the lower limb, transcranial stimulation provided increased heteronymous Ia facilitation and decreased D1 inhibition, both of which suggest a decrease in presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial stimulation provided an increase in the radial-induced inhibition of the wrist flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in single units, both of which suggest an increase in presynaptic inhibition. Selectivity of corticospinal effects was explored by testing presynaptic inhibition of Ia afferents to soleus motoneurones and focusing the transcranial stimulation to excite preferentially different motor nuclei (soleus, quadriceps and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of Ia afferents was seen when, and only when, cortical and peripheral Ia volleys were directed to the same motor nucleus. Received: 18 July 1997 / Accepted: 10 November 1997     

Evidence for presynaptic inhibition of muscle spindle Ia afferents in man

A new method for estimating presynaptic inhibition of soleus (Sol) Ia fibres in man is introduced based on the assessment of the amount of facilitation produced by a preceding homonymous Ia volley onto a Sol monosynaptic reflex. It was found in animal experiments that a reduction of such Ia facilitation reflects the amount of presynaptic inhibition exerted on these Ia fibres. Since, in man, a similar reduction of homonymous Ia facilitation was found after tibialis anterior vibration, this provides evidence for presynaptic inhibition of Sol Ia fibres, elicited here by the afferent discharge due to this flexor vibration.     

Recurrent inhibition of interneurones monosynaptically activated from group Ia afferents

1. Interneurones monosynaptically excited from large muscle spindle (Ia) afferents and inhibited from motor axon collaterals were searched for in the lumbar spinal cord of the cat.2. Monosynaptic Ia excitation was found in sixty-seven of sixty-nine interneurones inhibited by antidromic volleys. These interneurones were excited from Ia afferents from one or a few muscles (mainly close synergists). Volleys in high threshold muscle and skin afferents (FRA) evoked polysynaptic excitation or inhibition. Weak inhibition from Ia afferents (from antagonists to those giving Ia excitation) was seen in a few cells. Monosynaptic excitation was evoked from the ventral quadrant of the spinal cord and polysynaptic excitation from the dorsal quadrant.3. Inhibition from motor axon collaterals was evoked with a latency (1.2-2.0 msec) suggesting a disynaptic linkage and had the same time course as in motoneurones. It prevented synaptic activation of 60% of interneurones and decreased the firing index and delayed generation of spikes in the remaining.4. The interneurones with convergence of monosynaptic Ia excitation and inhibition from motor axon collaterals were found in the ventral horn dorsomedial to motor nuclei. No inhibition by antidromic volleys could be detected in interneurones located in intermediate nucleus and activated monosynaptically from Ia, Ib, group I or cutaneous afferents.5. It was concluded that the ventral Ia interneurones inhibited by volleys in recurrent motor axon collaterals mediate the reciprocal Ia inhibition to motoneurones.     

Modulation of presynaptic inhibition of Ia 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.     

Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static γ-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents.     

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

Summary 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).     

Impulse patterns of Ia afferents and Ia-activated DSCT neurons during sinusoidal muscle stretch in cats

Summary The cat gastrocnemius muscles of one hind leg were stretched sinusoidally with amplitudes between 10 m and 2.5 mm and frequencies between 1 and 30 Hz. The stretch response of deefferented muscle spindle afferents and of Ia-activated cells within Clarke's column were investigated by means of extra-cellular recordings of action potentials. The responses to 20–50 cycles were displayed in impulse patterns (raster diagrams) of the responding action potentials. The impulse patterns of Ia afferents exhibited a high degree of phase-locking (regularity) on the stretch cycle of amplitudes of about 50 m at 3 Hz and all higher amplitudes or frequencies. At comparable stretch parameters the regularity in Ia afferents was 4–6 times larger than in Ia-activated DSCT neurons. The regularity in the DSCT patterns increased with an increase in stretch frequency. The impulse patterns of DSCT cells exhibited a high negative correlation between successive interspike intervals (–0.4 to –0.6) at low stretch frequencies (<3 Hz), which decreased with an increase in stretch frequency.     

Task- and time-dependent modulation of Ia presynaptic inhibition during fatiguing contractions performed by humans

Presynaptic modulation of Ia afferents converging onto the motor neuron pool of the extensor carpi radialis (ECR) was compared during contractions (20% of maximal force) sustained to failure as subjects controlled either the angular position of the wrist while supporting an inertial load (position task) or exerted an equivalent force against a rigid restraint (force task). Test Hoffmann (H) reflexes were evoked in the ECR by stimulating the radial nerve above the elbow. Conditioned H reflexes were obtained by stimulating either the median nerve above the elbow or at the wrist (palmar branch) to assess presynaptic inhibition of homonymous (D1 inhibition) and heteronymous Ia afferents (heteronymous Ia facilitation), respectively. The position task was briefer than the force task (P = 0.001), although the maximal voluntary force and electromyograph for ECR declined similarly at failure for both tasks. Changes in the amplitude of the conditioned H reflex were positively correlated between the two conditioning methods (P = 0.02) and differed between the two tasks (P < 0.05). The amplitude of the conditioned H reflex during the position task first increased (129 ± 20.5% of the initial value, P < 0.001) before returning to its initial value (P = 0.22), whereas it increased progressively during the force task to reach 122 ± 17.4% of the initial value at failure (P < 0.001). Moreover, changes in conditioned H reflexes were associated with the time to task failure and force fluctuations. The results suggest a task- and time-dependent modulation of presynaptic inhibition of Ia afferents during fatiguing contractions.     

Presynaptic control of group Ia afferents in relation to acquisition of a visuo-motor skill in healthy humans

Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty, a novel visuo-motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H-reflex. The slope of the H-reflex recruitment curve and the H-max/M-max ratio were depressed after repetition of the visuo-motor skill task and returned to baseline after 10 min. No changes were observed after the control task. To elucidate the mechanisms contributing to the H-reflex depression, we measured the size of the long-latency depression of the soleus H-reflex evoked by peroneal nerve stimulation (D1 inhibition) and the size of the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo-motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed in the disynaptic reciprocal Ia inhibition. Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) were also unchanged, suggesting that transmission in ascending pathways was unaltered following the visuo-motor skill task. Together these observations suggest that a selective presynaptic control of Ia afferents contributes to the modulation of sensory inputs during acquisition of a novel visuo-motor skill in healthy humans.     

Comparison of the effects of stimulating extensor group I afferents on cycle period during walking in conscious and decerebrate cats

Previous studies have reported that stimulation of group I afferents from extensor muscles prolongs stance duration during walking in decerebrate cats. The main objective of this investigation was to determine whether this phenomenon occurs during walking in conscious cats. In conscious cats without lesions of the central nervous system (CNS), stimulation of group I afferents in the lateral gastrocnemius/soleus (LGS) nerve during stance prolonged extensor burst duration and increased the cycle period in five of seven animals. The mean increases in cycle period were modest, ranging from 6 to 22%. In five of six animals that walked both quadrupedally and bipedally at the same rate, the effects on cycle period were stronger during bipedal stepping (18% mean increase in cycle period compared with 9%). The stimulated nerves were transected and the experimental procedure was usually delayed in the conscious animals for 2–3 days following implantation of the stimulating electrodes. To assess whether chronic axotomy of the LGS nerve was a factor in the decreased effectiveness, four of the cats with chronic nerve section were decerebrated and their LGS nerves were stimulated after the animals began to spontaneously walk on a motorized treadmill. In all four of these animals, the effects of stimulating the chronically cut LGS nerve on the step cycle period became stronger following decerebration. However, these effects were not as strong as those produced when an acutely sectioned LGS nerve was stimulated. During both quadrupedal and bipedal walking, stimulation of the LGS nerve increased the amplitude of the medial gastrocnemius (MG) electromyogram. The augmented activity of the MG muscle contributed to an increased extension of the ankle during stimulated steps. The conclusion from these experiments is that stimulation of the group I afferents in extensor nerves can prolong stance in the conscious cat, but this effect is weaker than in decerebrate animals. It is likely that transmission in the polysynaptic group I pathways controlling stance duration is regulated in a complex fashion by descending signals from the brain in the conscious animal. Received: 6 December 1996 / Accepted: 4 June 1997     

Differential presynaptic inhibition of actions of group II afferents in di- and polysynaptic pathways to feline motoneurones

The aim of this study was to investigate differences in the effects of presynaptic inhibition of transmission from group II muscle afferents to neurones in the dorsal horn and in the intermediate zone and the consequences of these differences for reflex actions of group II afferents upon α-motoneurones. The degree of presynaptic inhibition was estimated from the degree of depression of monosynaptic components of population EPSPs (field potentials) evoked by group II muscle afferents in deeply anaesthetized cats. The decrease in the area of field potentials was considerably larger and longer lasting in the intermediate zone, where they were often obliterated, than in the dorsal horn, where they were reduced to about two-thirds. Presynaptic inhibition of field potentials evoked by other afferents at the same locations was much weaker. Intracellular records from α-motoneurones revealed that short latency EPSPs and IPSPs evoked from group II afferents are considerably reduced by conditioning stimuli that effectively depress intermediate zone field potentials of group II origin. The results of this study lead to the conclusion that strong presynaptic inhibition of transmission to intermediate zone interneurones allows a selective depression of disynaptic actions of group II muscle afferents on α- and γ-motoneurones, mediated by these interneurones, and favours polysynaptic actions of these afferents.     

Contribution of group III and IV muscle afferents to multisensorial spinal motor control in cats

The contribution of group III and IV muscle afferents to multisensorial segmental reflex pathways was investigated by testing for spatial facilitation between these afferents and non-nociceptive segmental afferents from skin, muscles and joints on postsynaptic potentials (PSPs) in alpha-motoneurones recorded in anaemically decapitated high spinal cats. Group III and IV muscle afferents were activated by intraarterial injection of potassium chloride (320 mM) or bradykinin triacetate (81 microM). Skin, joint and group I-II muscle afferents were stimulated by graded electrical stimulation of various nerves. Conditioning by stimulation of group III and IV muscle afferents spatially facilitated the transmission in segmental reflex pathways from low- to medium-threshold cutaneous and joint afferents as well as from lb and group II muscle afferents. Both excitatory and inhibitory pathways from these afferents were facilitated. Monosynaptic excitation and disynaptic antagonistic inhibition from group Ia afferents remained unaffected. It is concluded that the spatial facilitation observed between group III and IV muscle afferents and the other afferents indicate a convergence from group III and IV muscle afferents and the other afferents on common interneurones in segmental flexor reflex pathways. Under physiological conditions they thus contribute to the multisensorial feedback of the flexor reflex pathways. Pathophysiologically, the observed convergence may aggravate muscle weakness and atrophy of muscles induced by group III and IV muscle afferents.     

Comparison of effects of monoamines on transmission in spinal pathways from group I and II muscle afferents in the cat

Summary The actions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT; serotonin) were compared with those of L-3,4-dihydroxyphenylalanine methyl ester (Methyl-L-DOPA) on transmission to spinal interneurones in mid-lumbar (L4 and L5) segments of the cat spinal cord. The drugs were applied ionophoretically and their effects were tested on monosynaptic field potentials evoked by nerve impulses in hindlimb group I and group II muscle afferent fibres and on responses of interneurones with synaptic input from these fibres. Of field potentials recorded at various locations, both NA and 5-HT depressed those evoked from group II fibres in the intermediate and ventral horn regions of the spinal cord but not, or only occasionally, in the dorsal horn. Field potentials of group I origin were not depressed. The tested interneurones were located where group II field potentials were affected. NA, 5-HT and Methyl-L-DOPA depressed responses to electrical stimulation of group II fibres but not responses evoked by group I fibres. The depression consisted of an increase in the latency and a decrease in the number of action potentials evoked by the stimuli. All three drugs were also found to decrease the amplitude of intracellularly recorded monosynaptic EPSPs of group II origin but not of monosynaptic EPSPs evoked in the same neurones by group I fibres. Interneuronal firing induced by DL-homocysteic acid was depressed as effectively as responses to electrical stimulation of peripheral nerves. The possibility of presynaptic and/or postsynaptic mechanisms of the selective depression of synaptic actions of group II origin are discussed.