Non-monosynaptic Excitation Research Articles

Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii.

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments.

Group I projections from intrinsic foot muscles to motoneurones of leg and thigh muscles in humans.

1. Group I projections from intrinsic plantar muscles to motoneurones (MNs) of human leg and thigh muscles were investigated. Changes in firing probability of single motor units (MUs) in the tibialis anterior (TA), peroneus brevis (Per brev), soleus (Sol), gastrocnemius medialis (GM), vastus lateralis (VL), semitendinosus (ST) and biceps (Bi) were studied after electrical stimuli applied to: (i) the tibial nerve (TN) at ankle level, (ii) the corresponding homonymous nerve, and (iii) the skin of the heel, to mimic the TN-induced cutaneous sensation. 2. Homonymous facilitation, attributable to monosynaptic Ia excitation, was found in all the sampled units. Early heteronymous excitation elicited by TN stimulation was found in many MUs. Later effects (3-5 ms central delay) were bigger and more frequently observed: excitation in most TA and Per brev MUs, and inhibition in most Sol, GM and Bi MUs and in many ST and VL MUs. The low threshold (approximately 0.5-0.6 x motor threshold) and the inability of a pure cutaneous stimulation to reproduce these effects (except the late excitation in TA MUs) indicate that they were due to stimulation of group I muscle afferents. 3. The early excitation was accepted to be monosynaptic when its central delay differed from that of the homonymous Ia excitation by less than 0.5 ms. Such a significant TN-induced monosynaptic Ia excitation was found in MUs belonging to all leg and thigh motor nuclei tested. Although its mean strength was relatively weak, it is argued that these monosynaptic connections might affect already depolarized MNs. 4. The late excitation found in TA and Per brev MUs is argued to be mediated through interneurones located rostral to MNs. 5. The late suppression, found in most Sol, GM and Bi MUs, and in many ST and VL MUs, was the dominant effect. It was accompanied by an inhibition of the Sol and quadriceps H reflexes at rest, and therefore reflects an inhibition directed to MNs. Its long latency is argued to reflect transmission by interneurones located rostral to MNs (the inhibitory counterpart of non-monosynaptic excitation). 6. The functional implications of these connections are discussed with respect to the requirements of the stance phase of human walking and running.

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.

Group I extensor afferents evoke disynaptic EPSPs in cat hindlimb extensor motorneurones during fictive locomotion.

1. Intracellular recording from extensor motoneurones in paralysed decerebrate cats was used to examine the distribution of short-latency non-monosynaptic excitation by group I afferents during fictive locomotion produced by stimulation of the mesencephalic locomotor region (MLR). 2. During the extension but not the flexion phase of fictive locomotion, stimulation of ankle extensor nerves at 1.2-2.0 times threshold evoked excitatory postsynaptic potentials (EPSPs) in motoneurones innervating hip, knee and ankle extensors. Disynaptic EPSPs were also evoked by selective activation of group Ia muscle spindle afferents by muscle stretch. 3. The central latencies of these group I-evoked EPSPs (mean, 1.55 ms) suggest their mediation by a disynaptic pathway with a single interneurone interposed between extensor group I afferents and extensor motoneurones. Disynaptic EPSPs were also evoked during periods of spontaneous locomotion following the cessation of MLR stimulation. 4. Hip extensor motoneurones received disynaptic EPSPs during extension following stimulation of both homonymous and ankle extensor nerves. Stimulation of hip extensor nerves did not evoke disynaptic EPSPs in ankle extensor motoneurones. 5. The appearance of disynaptic EPSPs during extension appears to result from cyclic disinhibition of an unidentified population of excitatory spinal interneurones and not postsynaptic voltage-dependent conductances in motoneurones or phasic presynaptic inhibition of group I afferents during flexion. 6. The reorganization of group I reflexes during fictive locomotion includes the appearance of disynaptic excitation of hip, knee and ankle extensor motoneurones. This excitatory reflex is one of the mechanisms by which group I afferents can enhance extensor activity and increase force production during stance.

Evidence for corticospinal excitation of presumed propriospinal neurones in man.

1. The possibility that stimulation of the motor cortex facilitates transmission in the pathway mediating non-monosynaptic ('propriospinal') excitation from low-threshold afferents to upper limb motoneurones was investigated. 2. Convergence between peripheral afferent volleys (from the ulnar or musculo-cutaneous nerve) and corticospinal volleys (evoked by magnetic stimulation of the motor cortex) was investigated using the spatial facilitation technique. Thus the effects of these volleys on the flexor carpi radialis H reflex were compared when applied separately and together. When cortical stimulation was optimal for the muscle from which the conditioning volley originated the facilitation of the reflex on combined stimulation was significantly larger than the algebraic sum of the effects of separate stimuli. 3. The extra facilitation on combined stimulation had all the characteristics of 'propriospinal' excitation (low threshold, long central delay, brief duration and depression when the afferent input was increased), and it is suggested that this reflects corticospinal excitation of 'propriospinal' neurones. 4. When varying the time interval between cortical and test stimulations, it was shown that extra facilitation on combined stimulation began 1 ms later than the onset of the control reflex facilitation. Assuming that the latter onset reflects the arrival of the monosynaptic corticospinal volley at the motoneurone pool, this 1 ms delay suggests a disynaptic pathway for the cortical excitation of motoneurones through 'propriospinal' neurones. 5. As at the onset of voluntary movement, the pattern of the cortical excitation of 'propriospinal' neurones was quite specific: extra facilitation of the reflex on combined stimulation only occurred when the cortical volley was preferentially directed to motoneurones supplying the muscle from which the afferents used for the peripheral volley originated. 6. It is concluded that corticospinal axons activate human 'propriospinal' neurones and thereby produce disynaptic excitation of the motoneurone pool. Given temporal summation with the monosynaptic excitation, this 'propriospinally mediated' disynaptic excitation might make a significant contribution to the evoked EMG potential.

Pattern of propriospinal‐like excitation to different species of human upper limb motoneurones.

1. The pattern of distribution of non-monosynaptic (propriospinal-like) excitation to various motor nuclei (deltoid, extensors and flexors of the elbow, the wrist and the fingers) was investigated. 2. Changes in the firing probability of individual voluntarily activated motor units were studied following conditioning stimuli. Conditioning volleys were evoked by weak electrical stimuli applied to various mixed nerves (circumflex, musculocutaneous, median, radial, ulnar) and to the skin. 3. In all investigated nuclei stimulation of the 'homonymous' nerve evoked a peak of increased firing probability with a latency which was 2-7 ms longer than the monosynaptic Ia latency. The average central delay of the late excitation, measured from monosynaptic latency, seems to depend only on the segmental level of the motor nucleus: the more caudal the nucleus the longer the latency. This strongly suggest a transmission through neurones located above the cervical enlargement, as are C3--C4 propriospinal neurones in the cat. 4. Both group I muscle and cutaneous afferents were shown to contribute to propriospinal-like excitation. It is argued that a spatial facilitation of the effects evoked by these two inputs might explain why the threshold of late excitation is always below that of the monosynaptic Ia excitation in motoneurones. 5. The pattern of distribution of propriospinal-like excitation was diffuse: stimulation of each mixed nerve was able to evoke excitation in all investigated motor nuclei. Similarly, stimulation of a given skin field could produce excitation of biceps and wrist flexor and extensor units. 6. Each motor nucleus therefore receives excitation from a multimodal and wide range peripheral input. However, it is argued that what appears as a diffuse pattern might simply reflect connections which are not used in each movement but appropriately selected by higher centres.

Pattern of cutaneous inhibition of the propriospinal‐like excitation to human upper limb motoneurones.

1. The pattern of cutaneous inhibition of non-monosynaptic excitation (or 'propriospinal-like' excitation) to various species of motoneurones-wrist flexors and extensors, biceps and deltoid - was investigated in man. 2. Changes in the firing probability of individual voluntarily activated motor units were studied following various stimuli. The effects of weak cutaneous stimuli applied to the skin of either the palmar or the dorsal side of the fingers on propriospinal-like excitation evoked by stimulation of different mixed nerves (median, radial, musculo-cutaneous) were investigated. 3. Cutaneous stimuli were found to produce an inhibition with a very specific pattern, which depended on the afferent input evoking the excitation. Thus, the median nerve-induced excitation of wrist and elbow flexors was depressed by cutaneous afferents from the palmar side but not from the dorsal side of the fingers; the radial nerve-induced excitation of wrist extensors was only depressed from the dorsal side: the musculo-cutaneous nerve-induced excitation of motor units of various wrist, elbow and shoulder muscles was depressed from both sides. 4. It is argued that this pattern implies that the excitation is mediated to the motoneurones through different subsets of neurones, organized according to the afferent input. 5. The functional significance of the pattern of cutaneous inhibition is discussed and it is argued that it could contribute to an appropriately timed termination of a movement mediated through the propriospinal system.

Facilitation of transmission in the pathway of non-monosynaptic Ia excitation to wrist flexor motoneurones at the onset of voluntary movement in man

Homonymous Ia facilitation of the flexor carpi radialis (FCR) motoneurones (MNs) was significantly larger at the onset of voluntary wrist flexion than at rest. Similarly, stimulation of the ulnar nerve, which was without effect at rest, evoked a significant heteronymous facilitation at the onset of movement. In both cases this extra facilitation occurred with a central latency 3-3.5 ms longer than the monosynaptic latency and had a short (2-5 ms) duration. This long central latency corresponds to that of the recently described non-monosynaptic Ia excitation of FCR MNs. This suggests that interneurones mediating non-monosynaptic Ia excitation to FCR MNs receive strong descending excitation at the onset of movement, and it is argued that they could mediate part of the descending command to MNs.

Chapter 25 Peripheral and descending control of neurones mediating non-monosynaptic Ia excitation to motoneurones: a presumed propriospinal system in man

Evidence for a non-monosynaptic Ia excitation of wrist flexor and quadriceps motoneurones (MNs) in man has been provided while using two independent methods: construction of post-stimulus time histograms (PSTHs) of voluntarily activated motor units and the spatial facilitation of the H-reflex. This non-monosynaptic Ia excitation has a long central latency (3-6 ms) and a very low threshold. Neurones mediating this effect seem to receive a strong descending excitation at the onset of voluntary movement and it is argued that they might mediate part of the descending command to MNs. In contrast, increasing the afferent input produces an inhibition of the transmission in this pathway. Several characteristics of the non-monosynaptic excitation and its depression bear resemblance to those of the C3-C4 propriospinal system in the cat, which is used as a model for the discussion of the present results.

Inhibition of neurones transmitting non-monosynaptic Ia excitation to human wrist flexor motoneurones.

1. The possibility was investigated that the transmission of the interneuronally mediated Ia excitation to wrist flexor motoneurones described in the companion paper is inhibited by stimulation of afferent fibres. Two techniques were used: (i) the post-stimulus time histogram (PSTH) method for studying changes in firing probability of individual voluntarily activated wrist flexor motor units following various peripheral stimulations; and (ii) the indirect technique of spatial facilitation of the H reflex. 2. In those individual units where stimulation of the median and/or the ulnar nerve evoked a non-monosynaptic excitation, this excitation was reduced when the afferent input was increased. This reduction of the non-monosynaptic Ia excitation was found in 80% of the motor unit recordings, whether the afferent input was increased by increasing the stimulus intensity to one nerve or by using combined stimulation of two nerves. 3. Both group I muscle and low-threshold cutaneous afferents were shown to be able to reduce the non-monosynaptic Ia excitation. 4. The onset of the depression of the excitation was always found within the same 1 ms bin as that of the excitation. 5. Whatever the amount of afferent input (stimulus intensity increased up to motor threshold, spatial and temporal summation, summation of inhibitory effects from different origins), the depression could at the very most suppress the non-monosynaptic Ia excitation: i.e. a trough in the PSTH, reflecting an inhibition at the motoneuronal level, never appeared. In those units in which there was not non-monosynaptic excitation, peripheral stimulation did not evoke any inhibition appearing as a trough in the PSTH either. Hence, inhibition only appeared when there was a non-monosynaptic excitation, and then as a depression of it. 6. On the basis of these findings it is argued that the inhibition is not exerted directly onto motoneurones but acts at a pre-motoneuronal level on the interneurones mediating the non-monosynaptic Ia excitation to motoneurones. 7. Similarly, the homonymous non-monosynaptic Ia facilitation of the flexor carpi radialis H reflex was shown to be reduced by a preceding stimulation applied to the ulnar nerve. It is argued that this result is also compatible with an inhibition of transmission in interneuronal excitatory pathways to motoneurones. 8. It is suggested that the non-monosynaptic excitation of wrist flexor motoneurones in man and the inhibition of this excitation, both evoked by stimulation of low-threshold afferents, could be mediated through a system of cervical propriospinal neurones. Some aspects of the possible role of this system during movement are discussed.

Evidence for non-monosynaptic Ia excitation of human wrist flexor motoneurones, possibly via propriospinal neurones.

1. The possibility that activation of low-threshold afferents in the median and ulnar nerves in man evokes an interneuronally mediated excitation of wrist flexor motoneurones was investigated. Two independent techniques were used: (i) the indirect technique of spatial and temporal facilitation of the flexor carpi radialis H reflex; (ii) the post-stimulus time histogram (PSTH) method for measurement of the firing probability of voluntarily activated motor units following different stimuli. 2. Conditioning volleys were evoked by weak electrical stimuli (to the median nerve, the ulnar nerve, the skin and cutaneous nerve branches) and by a tap to the tendon of the flexor carpi radialis muscle. 3. In the H reflex experiments the comparison was drawn between the effects of two conditioning stimuli applied separately or together. In some experimental conditions the facilitation of the reflex evoked when combining two conditioning stimuli was larger than the algebraic sum of the effects from separate stimuli. The central latency of this additional facilitation, which is denoted 'extra facilitation', was 3 ms. It is argued that the extra facilitation reflects summation at a premotoneuronal level. 4. PSTHs of voluntarily activated flexor carpi radialis and flexor carpi ulnaris motor units were computed following stimulation of the median or the ulnar nerve. In 60% of the recordings the afferent volley evoked a peak of increased firing probability with a latency which was 3-6 ms longer than the monosynaptic Ia latency. 5. Both the extra facilitation of the reflex and the late peak in the PSTH were evoked from very low-threshold afferents. A contribution from Ia afferents was demonstrated in reflex experiments. Group I afferents alone are responsible for the onset of the non-monosynaptic excitation but it is probable that cutaneous afferents give a later contribution. 6. On the basis of the characteristics of the non-monosynaptic excitation studied with the two methods (same very low-threshold, comparable central latencies), it is argued that both the extra facilitation of the H reflex on combined stimulation and the late peak in the PSTHs from individual motor units are mediated through the same pre-motoneuronal pathway. 7. The possibility that the non-monosynaptic excitation may be mediated through propriospinal neurones is discussed.

Evidence that low threshold afferents both evoke and depress polysynaptic excitation of wrist flexor motoneurones in man.

The post-stimulus time histogram method was used to measure the time course of the firing probability of voluntarily activated wrist flexors motor units (MUs) after various stimulations. Stimulating the median and the ulnar nerve at an intensity equal to the motor threshold evoked an early increase in firing probability attributed to the monosynaptic Ia EPSP. Reducing the stimulation strength led to the disappearance of this peak and to the appearance of a second peak, whose latency was 3-5 ms longer than that of the monosynaptic peak. It is shown that both group I and cutaneous fibres contribute to the long-latency response but that group I fibres alone are responsible for its onset. Combined stimulation of the same afferents (group I and low threshold cutaneous fibres) reduced the amplitude of the second response. It is argued that this inhibition is exerted onto the interneurones mediating the non-monosynaptic excitation to motoneurones.