S A Edgley

An interneuronal relay for group I and II muscle afferents in the midlumbar segments of the cat spinal cord.

1. The properties of interneurones located in the 4th lumbar segment of the cat spinal cord (L4 interneurones) have been investigated by intracellular and extracellular recording from individual neurones. The study focused on interneurones projecting to hind‐limb motor nuclei and/or interposed in pathways from group II muscle afferents. The projection to motor nuclei was assessed from antidromic activation of the neurones by stimuli applied in the motor nuclei of the 7th lumbar (L7) segment. 2. Interneurones which projected to gastrocnemius‐soleus or hamstring motor nuclei were found in laminae VI and VII and at the border between laminae VII and VIII. The dominant peripheral input to most of them was from group II muscle afferents, but they were also influenced by group I muscle afferents and by afferents in cutaneous, joint and interosseous nerves. Both excitatory post‐synaptic potentials (e.p.s.p.s) and inhibitory post‐synaptic potentials (i.p.s.p.s) were evoked from all of these fibre systems. 3. The same kind of multimodal input was also found in other interneurones in laminae VI and VII. However, their axonal projections were not identified and they might have included neurones projecting to motor nuclei (though outside the areas which were stimulated) as well as neurones with more local actions. 4. Interneurones located in laminae IV and V of the dorsal horn appeared to constitute a separate functional population since both their projections and their input differed from those of the more ventrally located interneurones; none of the dorsal horn interneurones were found to project to motor nuclei and none had input from group I afferents, although they were influenced by group II muscle afferents and by afferents in cutaneous, joint and interosseous nerves. 5. Many of the excitatory actions from group I and II afferents upon L4 interneurones were found to be evoked monosynaptically. A high proportion of L4 neurones synapsing upon motoneurones would thus be interposed in disynaptic reflex pathways from these afferents. In comparison to actions evoked via interneurones of the caudal lumbar segments, any post‐synaptic potentials (p.s.p.s) evoked via L4 interneurones would be delayed. These delays would amount to 0.4‐0.9 ms for p.s.p.s. from group I afferents and by 0.5‐2.5 ms for group II p.s.p.s. 6. In many interneurones, particularly those located ventrally, i.p.s.p.s. were evoked by group I and II muscle afferents at latencies which indicated that they were evoked disynaptically. They may therefore reflect inhibitory interactions between subpopulations of L4 interneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitation of the corticospinal tract by electromagnetic and electrical stimulation of the scalp in the macaque monkey.

1. The responses evoked by non‐invasive electromagnetic and surface anodal electrical stimulation of the scalp (scalp stimulation) have been studied in the monkey. Conventional recording and stimulating electrodes, placed in the corticospinal pathway in the hand area of the left motor cortex, left medullary pyramid and the right spinal dorsolateral funiculus (DLF), allowed comparison of the actions of non‐invasive stimuli and conventional electrical stimulation. 2. Responses to electromagnetic stimulation (with the coil tangential to the skull) were studied in four anaesthetized monkeys. In each case short‐latency descending volleys were recorded in the contralateral DLF at threshold. In two animals later responses were also seen at higher stimulus intensities. Both early and late responses were of corticospinal origin since they could be completely collided by appropriately timed stimulation of the pyramidal tract. The latency of the early response in the DLF indicated that it resulted from direct activation of corticospinal neurones: its latency was the same as the latency of the antidromic action potentials evoked in the motor cortex from the recording site in the DLF. 3. Scalp stimulation, which was also investigated in three of the monkeys, evoked short‐latency volleys at threshold and at higher stimulus intensities these were followed by later waves. The short‐latency volleys could be collided from the pyramid and, at threshold, had latencies compatible with direct activation of corticospinal neurones. The longer latency volleys were also identified as corticospinal in origin. 4. The latency of the early volley evoked by electromagnetic stimulation remained constant with increasing stimulus intensities. In contrast, with scalp stimulation above threshold the latency of the early volleys decreased considerably, indicating remote activation of the corticospinal pathway below the level of the motor cortex. In two monkeys both collision and latency data suggest activation of the corticospinal pathway as far caudal as the medulla. 5. The majority of fast corticospinal fibres could be excited by scalp stimulation with intensities of 20% of maximum stimulator output. Electromagnetic stimulation at maximum stimulator output elicited a volley of between 70 and 90% of the size of the maximal volley evoked from the pyramidal electrodes. 6. Electromagnetic stimulation was also investigated in one awake monkey during the performance of a precision grip task. Short‐latency EMG responses were evoked in hand and forearm muscles. The onsets of these responses were approximately 0.8 ms longer than the responses evoked by electrical stimulation of the pyramid.(ABSTRACT TRUNCATED AT 400 WORDS)

Post‐synaptic actions of midlumbar interneurones on motoneurones of hind‐limb muscles in the cat.

1. The hypothesis that interneurones in the 4th lumbar segment (L4) are interposed between group I and group II afferents and hind‐limb motoneurones has been tested. Action potentials of single interneurones were induced by ionophoretically applied homocysteate and recorded in parallel with post‐synaptic potentials in motoneurones; the latter were recorded from motor axons in the ventral root of the first sacral segment as population potentials, using the sucrose gap technique. 2. The action potentials of twenty‐four L4 interneurones were found to be followed by either e.p.s.p.s. or i.p.s.p.s in motoneurones. The latencies of the majority of these p.s.p.s were consistent with monosynaptically evoked excitation or inhibition of motoneurones since they exceeded the latencies of antidromic activation of the interneurones from the S1 motor nuclei by only a fraction of a millisecond. 3. The dominant input to both the excitatory and the inhibitory interneurones was from group II muscle afferents, in particular from the quadriceps nerve. The latencies of excitation of the interneurones by these afferents indicated a monosynaptic coupling between them. The same interneurones were co‐excited by group I and cutaneous afferents and by descending fibres. 4. We conclude that not only excitation but also inhibition of hind‐limb motoneurones from group II afferents may be mediated disynaptically and that interneurones in the 4th lumbar segment contribute to both.

Direct and Indirect Connections with Upper Limb Motoneurons from the Primate Reticulospinal Tract

Although the reticulospinal tract is a major descending motor pathway in mammals, its contribution to upper limb control in primates has received relatively little attention. Reticulospinal connections are widely assumed to be responsible for coordinated gross movements primarily of proximal muscles, whereas the corticospinal tract mediates fine movements, particularly of the hand. In this study, we used intracellular recording in anesthetized monkeys to examine the synaptic connections between the reticulospinal tract and antidromically identified cervical ventral horn motoneurons, focusing in particular on motoneurons projecting distally to wrist and digit muscles. We found that motoneurons receive monosynaptic and disynaptic reticulospinal inputs, including monosynaptic excitatory connections to motoneurons that innervate intrinsic hand muscles, a connection not previously known to exist. We show that excitatory reticulomotoneuronal connections are as common and as strong in hand motoneuron groups as in forearm or upper arm motoneurons. These data suggest that the primate reticulospinal system may form a parallel pathway to distal muscles, alongside the corticospinal tract. Reticulospinal neurons are therefore in a position to influence upper limb muscle activity after damage to the corticospinal system as may occur in stroke or spinal cord injury, and may be a target site for therapeutic interventions.

Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey

Damage to the corticospinal tract is a leading cause of motor disability, for example in stroke or spinal cord injury. Some function usually recovers, but whether plasticity of undamaged ipsilaterally descending corticospinal axons and/or brainstem pathways such as the reticulospinal tract contributes to recovery is unknown. Here, we examined the connectivity in these pathways to motor neurons after recovery from corticospinal lesions. Extensive unilateral lesions of the medullary corticospinal fibres in the pyramidal tract were made in three adult macaque monkeys. After an initial contralateral flaccid paralysis, motor function rapidly recovered, after which all animals were capable of climbing and supporting their weight by gripping the cage bars with the contralesional hand. In one animal where experimental testing was carried out, there was (as expected) no recovery of fine independent finger movements. Around 6 months post-lesion, intracellular recordings were made from 167 motor neurons innervating hand and forearm muscles. Synaptic responses evoked by stimulating the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus were recorded and compared with control responses in 207 motor neurons from six unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak in both lesioned and control animals, suggesting a limited role for this pathway in functional recovery. In contrast, mono- and disynaptic excitatory post-synaptic potentials elicited from the medial longitudinal fasciculus significantly increased in average size after recovery, but only in motor neurons innervating forearm flexor and intrinsic hand muscles, not in forearm extensor motor neurons. We conclude that reticulospinal systems sub-serve some of the functional recovery after corticospinal lesions. The imbalanced strengthening of connections to flexor, but not extensor, motor neurons mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors.

Evidence that mid-lumbar neurones in reflex pathways from group II afferents are involved in locomotion in the cat.

1. A group of interneurons in the mid‐lumbar segments of the cat spinal cord which mediate disynaptic excitation or inhibition of motoneurones from group II muscle afferents have recently been described. To test the possibility that the activity of these interneurones is related to the activity in the neuronal networks which subserve locomotion we have investigated whether they are influenced by two procedures which can induce locomotion. These procedures were electrical stimulation within the cuneiform nucleus (the ‘mesencephalic locomotor region’) in anaesthetized preparations and systemic administration of 3,4‐dihydroxyphenylalanine (DOPA) in decerebrate, spinalized, unanaesthetized preparations. The interneurones we have tested were located in the fourth lumbar (L4) segment and were excited by group II muscle afferents; more than half of them were antidromically activated from the hindlimb motor nuclei. 2. Stimuli applied in the cuneiform nucleus evoked excitatory postsynaptic potentials (EPSPs) in a high proportion of these interneurones. The stimuli also evoked distinct extracellular field potentials in the ventral horn of the L4 segment. The properties and latencies of both the intra‐ and extracellularly recorded potentials show that they were evoked disynaptically, via supraspinally located relay neurones and a fast‐conducting descending tract. 3. Stimulation of the cortico‐ and rubrospinal tracts excited or inhibited some of the L4 neurones, often at latencies suggesting mono‐ or disynaptic coupling. The neurones which appeared to be monosynaptically excited from the cortico‐ and rubrospinal tracts tended to be located dorsal to the neurones which were activated from the cuneiform nucleus. 4. Systemic administration of DOPA depressed the responses evoked by stimulation of group II afferents of L4 interneurones which projected to motor nuclei. DOPA also depressed extracellular field potentials evoked by group II afferents in the intermediate zone and in the ventral horn (at the location of the interneurones) but hardly affected those in the dorsal horn. 5. By showing that both stimulation in the cuneiform nucleus and the administration of DOPA influence activity of L4 interneurones which are excited by group II afferents and which project to motor nuclei, the results of this study support the hypothesis that these neurones are in some way involved in locomotion. However, the opposing effects of DOPA administration and of stimulation in the cuneiform nucleus make the interpretation of their role in locomotion rather difficult before it is known to what extent they are active throughout the step cycle.

Different responses of rat cerebellar Purkinje cells and Golgi cells evoked by widespread convergent sensory inputs

While the synaptic properties of Golgi cell‐mediated inhibition of granule cells are well studied, less is known of the afferent inputs to Golgi cells so their role in information processing remains unclear. We investigated the responses of cerebellar cortical Golgi cells and Purkinje cells in Crus I and II of the posterior lobe cerebellar hemisphere to activation of peripheral afferents in vivo, using anaesthetized rats. Recordings were made from 70 Golgi cells and 76 Purkinje cells. Purkinje cells were identified by the presence of climbing fibre responses. Golgi cells were identified by both spontaneous firing pattern and response properties, and identification was confirmed using juxtacellular labelling of single neurones (n= 16). Purkinje cells in Crus II showed continuous firing at relatively high rates (25–60 Hz) and stimulation of peripheral afferents rarely evoked substantial responses. The most common response was a modest, long‐latency, long‐lasting increase in simple spike output. By comparison, the most common response evoked in Golgi cells by the same stimuli was a long‐latency, long‐lasting depression of firing, found in ∼70% of the Golgi cells tested. The onsets of Golgi cell depressions had shorter latencies than the Purkinje cell excitations. Brief, short‐latency excitations and reductions in firing were also evoked in some Golgi cells, and rarely in Purkinje cells, but in most cases long‐lasting depressions were the only significant change in spike firing. Golgi cell responses could be evoked using air puff or tactile stimuli and under four different anaesthetic regimens. Long‐lasting responses in both neurone types could be evoked from wide receptive fields, in many cases including distal afferents from all four limbs, as well as from trigeminal afferents. These Golgi cell responses are not consistent with the conventional feedback inhibition or ‘gain control’ models of Golgi cell function. They suggest instead that cerebellar cortical activity can be powerfully modulated by the general level of peripheral afferent activation from much of the body. On this basis, Golgi cells may act as a context‐specific gate on transmission through the mossy fibre–granule cell pathway.

Field potentials generated by group II muscle afferents in the middle lumbar segments of the cat spinal cord.

1. A powerful projection from group II muscle afferents of hind‐limb muscles to the 3rd, 4th and 5th segments of the lumbar spinal cord has been demonstrated by focal synaptic field potential recording. 2. Field potentials were found at two locations: one in the dorsal horn (Rexeds laminae IV and V) and the other in the intermediate zone and ventral horn (Rexeds laminae VII and VIII). In the dorsal horn the field potentials were exceptionally large and were evoked only by group II afferents. At more ventral locations, they were smaller and were sometimes preceded by small field potentials evoked by group I afferents. 3. At both locations field potentials could be evoked by stimulation of a number of hind‐limb muscle nerves at strengths sufficient to activate group II afferents. However, some nerves consistently evoked more powerful effects than others and the largest potentials were from the nerves to quadriceps, sartorius and to the pretibial flexor muscles (tibialis anterior and extensor digitorum longus). Activation of articular afferents (from the knee joint nerve) or Pacinian corpuscle afferents (from the interosseous nerve) evoked small field potentials at some locations. 4. In the dorsal horn the latency of the field potentials was so short that they must have been generated monosynaptically. Field potentials in the ventral horn had longer latencies, by 0.5‐1.0 ms, but they also appear to have been monosynaptically evoked by slowly conducting intraspinal collaterals. This conclusion is based primarily on the effects of intraspinal stimulation which was found to antidromically activate afferents with the appropriate latencies and thresholds. 5. Evidence is presented that the dorsal and ventral field potentials are generated by afferents whose receptors can be activated by small (less than 100 micron) muscle stretches.

Complex spikes in Purkinje cells of the paravermal part of the anterior lobe of the cat cerebellum during locomotion.

1. The temporal pattern of the discharge of complex spikes by Purkinje cells in the paravermal cortex of the cerebellar lobule V b/c has been examined during locomotion in awake cats. 2. The peripheral receptive fields of 138 Purkinje cells were examined using light tactile stimulation. In 91% of these cells, complex spikes were evoked by stimuli applied to the ipsilateral forelimb and of eighty‐eight cells examined in most detail, 76% had receptive fields including the paw or wrist. Sixty‐six per cent had receptive fields restricted to the paw and/or wrist. 3. Complex spikes were not discharged at rigidly fixed times during the step cycle in any of sixty‐nine Purkinje cells which were recorded during locomotion on a moving belt. 4. When the discharges were averaged over many steps the probability of occurrence of complex spikes showed small fluctuations during the course of the step cycle, but these fluctuations were shown not to be statistically significantly different from those which could arise by chance. 5. These findings are inconsistent with previous suggestions (e.g. Armstrong, 1974; Rushmer, Roberts & Augter, 1976) that, during locomotion, the climbing fibres act to signal the occurrence of specific peripheral events, such as foot touch‐down or lift‐off.

Functional differentiation and organization of feline midlumbar commissural interneurones

Interneurones interconnecting the two sides of the spinal cord (commissural interneurones) are critically important for interlimb coordination, but little is known about their organization. We have examined the inputs to commissural interneurones located in the midlumbar segments with projections to contralateral motor nuclei, aiming to determine whether they form distinct subpopulations. Based on intracellular records from 78 interneurones, two major non‐overlapping subpopulations were identified: one monosynaptically excited by group II muscle afferents (n= 10), the other monosynaptically excited by reticulospinal neurones (n= 52). Monosynaptic input from group I muscle afferents and/or from vestibulospinal tract neurones was found in those with monosynaptic reticulospinal, but not group II input, and in a few other neurones (n= 6). Only disynaptic input from these sources was found in the remaining 10 interneurones. Disynaptic excitatory input from ipsilateral and contralateral muscle afferents and from descending tracts was distributed less selectively and might mediate coexcitation of interneurones with monosynaptic afferent or descending input. The dominant disynaptic and polysynaptic input was, however, inhibitory. IPSPs were evoked from the descending tracts in a high proportion of the commissural interneurones that were monosynaptically excited by group II afferents (55%) and from group II afferents in a high proportion of the commissural interneurones that were monosynaptically excited by reticulospinal fibres (78%). This distribution suggests that the two subpopulations are activated differentially, rather than being coactivated, in either centrally initiated movements or reflex adjustments. This would be consistent with the previous demonstration that noradrenaline differentially affects commissural neurones of the two subpopulations.