RESUMEN

Previous evidence from electrophysiological experiments in anaesthetized cats with a chronic lateral lesion of the lower thoracic spinal cord indicated an expansion of the functional projections of expiratory bulbospinal neurones (EBSNs) in the segment above the lesion, measured at 16 weeks post-lesion. Here we investigate connections made by the same EBSNs to motoneurones in that segment, using cross-correlations between their discharges. The connections to the internal intercostal nerve motoneurones were found to be no different from controls. However, a significant increase was found in the number of connections between EBSNs and γ motoneurones of the external intercostal nerve (8/24, compared to 1/16) with possibly additional connections to the α motoneurones of the same nerve. Increased connections to the γ motoneurones of the internal intercostal nerve could not be ruled out. The expanded functional projections are thus likely to include new connections to γ motoneurones. We suggest that γ motoneurones may be inherently more receptive to new inputs. If so, the previously discounted role of abnormal fusimotor discharges in motor disorders would be worth reconsideration.

Asunto(s)

RESUMEN

The morphology and projections of ventral horn interneurones in the segment above an ipsilateral thoracic lateral spinal cord lesion were studied in the cat by intracellular injections of Neurobiotin at 6 to 18 weeks post-lesion and compared with previously published control data from uninjured spinal cords. The cell axons ascended, descended or both, mostly contralaterally and mostly spared by the lesion. Unusual morphological dendritic features were seen in the lesion group, mostly growth-related, including complex dendritic appendages, twisted or multiple-branched terminal dendrites, commissural dendrites, apparently swollen proximal dendrites and rostrocaudal asymmetries. Significant quantitative differences included more dendritic spines in the lesion group (3.4×) and smaller soma areas in the lesion group (with similar numbers of primary dendrites and rostrocaudal dendritic spans). Immunoreactivity to microtubule associated protein 2a/b was detected in the proximal, but not distal, dendrites of cells in the lesion group, corresponding to an overall decrease in immunoreactivity in the ventral horns on the lesion side compared to the other. For axon collaterals, significant increases for the lesion group were seen in the number of collaterals in the first 4 mm of axon and in the area of ventral/intermediate horn occupied by terminals, including increased innervation of some regions, among which were the intermediolateral columns. This dendritic and axonal plasticity makes the interneuones candidates for a role in detour circuits but also for a maladaptive role in autonomic hyperreflexia.

Asunto(s)

RESUMEN

In animals, high-frequency spinal cord stimulation (HF-SCS) applied on the ventral epidural surface at the T2 level results in negative airway pressure generation consistent with inspiratory muscle activation. In the present study, in anesthetized dogs, we found that ventral HF-SCS (500 Hz) applied at all thoracic levels resulted in negative airway pressure generation. In the region of the lower thoracic spinal cord, negative airway pressure generation was most pronounced at the T9 level. At this level, airway pressure generation was monitored: 1) during ventral HF-SCS over a wide range of stimulus amplitudes (0.5-15 mA) and frequencies (50-1,000 Hz) and 2) following spinal sections at C8 (to assess potential diaphragm activation) and subsequently at T6 (to assess potential intercostal muscle activation). The application of low stimulus currents between 1 and 2 mA and high stimulus frequencies (>300 Hz) resulted in the development of large negative airway pressure generation. Stimulation with 1 mA, 500 Hz resulted in a highest negative airway pressure generation of 47 ± 2 cmH2O. Increasing stimulus current was associated with progressive reductions in the magnitude of negative airway pressure generation. HF-SCS (500 Hz) with 15 mA resulted in a negative airway pressure generation of 7 ± 3 cmH2O. C8 section markedly reduced negative airway pressure generation, and subsequent T6 section resulted in positive airway pressure generation after HF-SCS. Our results indicate the existence of pathways with connections to both the phrenic and inspiratory intercostal motoneuron pools in the ventral part of the lower thoracic spinal cord. We speculate that the circuits mediating the previously described excitatory intercostal-to-phrenic reflex mediate the observed responses. NEW & NOTEWORTHY This study suggests that, in contrast to dorsal high-frequency spinal cord stimulation at the T9 spinal level, which results in positive pressure generation, ventral high-frequency spinal cord stimulation at the same spinal level results in large negative airway pressure generation with low stimulus currents. This method, therefore, may provide an alternative method to restore ventilation in ventilator-dependent spinal cord-injured patients.

Asunto(s)

RESUMEN

There are hardly any published data on the characteristics of muscle nerve sympathetic discharges occurring in parallel with the somatic motoneurone discharges in the same nerves. Here, we take advantage of the naturally occurring respiratory activity in recordings of efferent discharges from branches of the intercostal and abdominal nerves in anesthetized cats to make this comparison. The occurrence of efferent spikes with amplitudes below that for alpha motoneurones were analyzed for cardiac modulation, using cross-correlation between the times of the R-wave of the ECG and the efferent spikes. The modulation was observed in nearly all recordings, and for all categories of nerves. It was strongest for the smallest amplitude spikes or spike-like waveforms, which were deduced to comprise postsynaptic sympathetic discharges. New observations were: (1) that the cardiac modulation of these discharges was modest compared to most previous reports for muscle nerves; (2) that the amplitudes of the sympathetic discharges compared to those of the somatic spikes were strongly positively correlated to nerve diameter, such that, for the larger nerves, their amplitudes overlapped considerably with those of gamma motoneurone spikes. This could be explained by random summation of high rates of unit sympathetic spikes. We suggest that under some experimental circumstances this overlap could lead to considerable ambiguity in the identity of the discharges in efferent neurograms.

Asunto(s)

Asunto(s)

RESUMEN

In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves). Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2) and spontaneously occurring locomotor drive potentials (LDPs) in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves), with a slow rate (periods 9-104 s, mean 39 ± 17 SD). Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated.

Asunto(s)

RESUMEN

The respiratory activity in the intercostal nerves of the rat is unusual, in that motoneurones of both branches of the intercostal nerves, internal and external, are activated during expiration. Here, the pathways involved in that activation were investigated in anaesthetised and in decerebrate rats by cross-correlation and by intracellular spike-triggered averaging from expiratory bulbospinal neurones (EBSNs), with a view to revealing specific connections that could be used in studies of experimental spinal cord injury. Decerebrate preparations, which showed the strongest expiratory activity, were found to be the most suitable for these measurements. Cross-correlations in these preparations showed monosynaptic connections from 16/19 (84%) of EBSNs, but only to internal intercostal nerve motoneurones (24/37, 65% of EBSN/nerve pairs), whereas disynaptic connections were seen for external intercostal nerve motoneurones (4/19, 21% of EBSNs or 7/25, 28% of EBSN/nerve pairs). There was evidence for additional disynaptic connections to internal intercostal nerve motoneurones. Intracellular spike-triggered averaging revealed excitatory postsynaptic potentials, which confirmed these connections. This is believed to be the first report of single descending fibres that participate in two different pathways to two different groups of motoneurones. It is of interest compared with the cat, where only one group of motoneurones is activated during expiration and only one of the pathways has been detected. The specificity of the connections could be valuable in studies of plasticity in pathological situations, but care will be needed in studying connections in such situations, because their strength was found here to be relatively weak.

Asunto(s)

RESUMEN

The responses of individual primate corticospinal neurons to localized electrical stimulation of primary motor (M1) and of ventral premotor cortex (area F5) are poorly documented. To rectify this and to study interactions between responses from these areas, we recorded corticospinal axons, identified by pyramidal tract stimulation, in the cervical spinal cord of three chloralose-anesthetized macaque monkeys. Single stimuli (≤400 µA) were delivered to the hand area of M1 or F5 through intracortical microwire arrays. Only 14/112 (13%) axons showed responses to M1 stimuli that indicated direct intracortical activation of corticospinal neurons (D-responses); no D-responses were seen from F5. In contrast, 62 axons (55%) exhibited consistent later responses to M1 stimulation, corresponding to indirect activation (I-responses), showing that single-pulse intracortical stimulation of motor areas can result in trans-synaptic activation of a high proportion of the corticospinal output. A combined latency histogram of all axon responses was nonperiodic, clearly different from the periodic surface-recorded corticospinal volleys. This was readily explained by correcting for conduction velocities of individual axons. D-responding axons, taken as originating in neurons close to the M1 stimulating electrodes, showed more I-responses from M1 than those without a D-response, and 8/10 of these axons also responded to F5 stimulation. Altogether, 33% of tested axons responded to F5 stimulation, most of which also showed I-responses from M1. These excitatory effects are in keeping with facilitation of hand muscles evoked from F5 being relayed via M1. This was further demonstrated by facilitation of test responses from M1 by conditioning F5 stimuli.

Asunto(s)

RESUMEN

Renshaw cells are widely distributed in all segments of the spinal cord, but detailed morphological studies of these cells and their axonal branching patterns have only been made for lumbosacral segments. For these, a characteristic distribution of terminals was reported, including extensive collateralization within 1-2 mm of the soma, but then more restricted collaterals given off at intervals from the funicular axon. Previous authors have suggested that the projections close to the soma serve inhibition of motoneurons (known to be greatest for the motor nuclei providing the Renshaw cell excitation) but that the distant projections serve mainly the inhibition of other neurons. However, in thoracic segments, inhibition of motoneurons is known to occur over two to three segments (20-40 mm) from the presumed somatic locations of the Renshaw cells. Here, we report the first detailed morphological study of Renshaw cell axons outside the lumbosacral segments, which investigated whether this different distribution of motoneuron inhibition is reflected in a different pattern of Renshaw cell terminations. Four Renshaw cells in T7 or T8 segments were intracellularly labeled with neurobiotin in anesthetized cats and their axons traced for distances ≥6 mm from the somata. The only morphological difference detected within this distance in comparison with Renshaw cells in the lumbosacral cord was a minimal taper in the funicular axons, where in the lumbosacral cord this is pronounced. Patterns of termination were virtually identical to those in the lumbosacral segments, so we conclude that these patterns are unrelated to the pattern of motoneuronal inhibition.

Asunto(s)

RESUMEN

The nervous control of expiratory muscles is less well understood than that of the inspiratory muscles, particularly in the rat. The patterns of respiratory discharges in adult rats were therefore investigated for the muscles of the caudal intercostal spaces, with hypercapnia and under either anaesthesia or decerebration. With neuromuscular blockade and artificial ventilation, efferent discharges were present for both inspiration and expiration in both external and internal intercostal nerves. This was also the case for proximal internal intercostal nerve branches that innervate only internal intercostal and subcostalis muscles. If active, this region of muscle in other species is always expiratory. Here, inspiratory bursts were almost always present. The expiratory activity appeared only gradually and intermittently, when the anaesthesia was allowed to lighten or as the pre-decerebration anaesthesia wore off. The intermittent appearance is interpreted as the coupling of a slow medullary expiratory oscillator with a faster inspiratory one. The patterns of nerve discharges, in particular the inspiratory or biphasic activation of the internal and subcostalis layers, were confirmed by observations of equivalent patterns of EMG discharges in spontaneously breathing preparations, using denervation procedures to identify which muscles generated the signals. Some motor units were recruited in both inspiratory and expiratory bursts. These patterns of activity have not previously been described and have implications both for the functional role of multiple respiratory oscillators in the adult and for the mechanical actions of the muscles of the caudal intercostal spaces, including subcostalis, which is a partly bisegmental muscle.

Asunto(s)

RESUMEN

Intracellular recordings were made from motoneurones with axons in the intercostal nerves of T9 or T10 in adult rats, with neuromuscular blockade and artificial ventilation, under hypercapnia and under either anaesthesia or decerebration. In nearly all motoneurones, central respiratory drive potentials (CRDPs) were seen, which included an excitatory wave in inspiration, in expiration, or in both of these. This was the case both for motoneurones with axons in the internal intercostal nerve (n = 81) and for those with axons in the external intercostal nerve (n = 5). In the decerebrates, motoneurones with purely inspiratory CRDPs were rare (1/44), but those excited in both phases (showing biphasic CRDPs) were common (22/44). For about one-third of biphasic CRDPs (11/30), the inspiratory depolarization was seen to reverse to a hyperpolarization when the motoneurone was depolarized, which was interpreted as indicating concurrent inhibition and excitation during this phase. A few motoneurones were seen where depolarization revealed signs of inhibition in both phases. The results confirm the novel observations of biphasic excitation in individual intercostal nerve branches, EMG sites and motor units reported in a companion paper. They also provide new insights into the functional roles of inhibition in motoneurones physiologically activated in natural rhythmic behaviours.

Asunto(s)

RESUMEN

The incurability of spinal cord injury and subcortical strokes is due to the inability of nerve fibres to regenerate. One of the clearest clinical situations where failure of regeneration leads to a permanent functional deficit is avulsion of the brachial plexus. In current practice, surgical re-implantation of avulsed spinal roots provides a degree of motor recovery, but the patients neither recover sensation nor the use of the hand. In the present rat study, we show that transplantation of cultured adult olfactory ensheathing cells restores the sensory input needed for a complex, goal-directed fore-paw function and re-establishes synaptic transmission to the spinal grey matter and cuneate nucleus by providing a bridge for regeneration of severed dorsal root fibres into the spinal cord. Success in a first application of human olfactory ensheathing cells in clinical brachial plexus injury would open the way to the wider field of brain and spinal cord injuries.

Asunto(s)

RESUMEN

The rubrospinal tract (RST) of the rat is widely used in studies of regeneration and plasticity, but the electrophysiology of its spinal actions has not been described. In anaesthetised rats with neuromuscular blockade, a tungsten microelectrode was located in the region of the red nucleus (RN) by combining stereotaxis with recording of antidromic potentials evoked from the contralateral spinal cord. Single stimuli through this electrode typically elicited two descending volleys in the contralateral dorsolateral funiculus (DLF) separated by about 1 ms, and one volley recorded from the ipsilateral DLF. Latencies of the ipsilateral and the early contralateral volley were similar. The activation of these volleys depended on the location of the stimulation site in or near the RN. Evidence is adduced to show that: (a) the late contralateral volley is carried by fibres of RST neurones, synaptically activated; (b) the early contralateral volley is mostly carried by RST fibres stimulated directly; (c) the ipsilateral volley is sometimes carried by RST fibres from the RN on the side contralateral to the stimulus; (d) otherwise, either early volley may derive from fibres in other tracts. Synaptic potentials related to the volleys were recorded within the cervical enlargement and their distribution plotted on cross-sections of the spinal cord. These measurements suggest that the great majority of RST terminations are on interneurones in the intermediate region contralateral to the RN. Direct synaptic actions on motoneurones are likely to be weak. Stimulation parameters appropriate for specific activation of the RST in future studies are suggested.

Asunto(s)

RESUMEN

In common with other secondary motor areas, the macaque ventral premotor cortex (PMv) gives rise to corticospinal projections; it also makes numerous reciprocal corticocortical connections with the primary motor cortex (M1). Repetitive intracortical microstimulation (rICMS) of the PMv gives rise to movements of the hand and digits. To investigate whether these motor effects are dependent on the corticocortical interactions with M1, the effect of reversible inactivation of the M1 hand area was tested in three macaque monkeys with chronically implanted intracortical electrodes in the hand representations of M1 and PMv (rostral division, area F5). Monkeys were lightly sedated. Test EMG responses to rICMS were recorded from intrinsic hand muscles before and after microinjection of the GABA agonist muscimol in the M1 hand area. This not only greatly reduced EMG responses evoked from M1, but also reduced or abolished responses from F5, over a similar time course (20-50 min). Muscimol in M1 reduced the level of background EMG activity in the contralateral hand, which was paretic for several hours after injection. However, because EMG responses to direct activation of the corticospinal tract were significantly less affected than the responses to F5 stimulation, it is unlikely that reduced motoneuronal excitability explained the loss of the evoked responses from F5. Finally, muscimol injections in M1 greatly reduced the corticospinal volleys evoked by rICMS in F5. The results suggest that the motor effects evoked from F5 depend, at least in part, on corticocortical interactions with M1, leading to activation of M1 corticospinal outputs to hand muscles.

Asunto(s)

RESUMEN

The mechanical advantages of the external and internal intercostals depend partly on the orientation of the muscle but mostly on interspace number and the position of the muscle within each interspace. Thus the external intercostals in the dorsal portion of the rostral interspaces have a large inspiratory mechanical advantage, but this advantage decreases ventrally and caudally such that in the ventral portion of the caudal interspaces, it is reversed into an expiratory mechanical advantage. The internal interosseous intercostals in the caudal interspaces also have a large expiratory mechanical advantage, but this advantage decreases cranially and, for the upper interspaces, ventrally as well. The intercartilaginous portion of the internal intercostals (the so-called parasternal intercostals), therefore, has an inspiratory mechanical advantage, whereas the triangularis sterni has a large expiratory mechanical advantage. These rostrocaudal gradients result from the nonuniform coupling between rib displacement and lung expansion, and the dorsoventral gradients result from the three-dimensional configuration of the rib cage. Such topographic differences in mechanical advantage imply that the functions of the muscles during breathing are largely determined by the topographic distributions of neural drive. The distributions of inspiratory and expiratory activity among the muscles are strikingly similar to the distributions of inspiratory and expiratory mechanical advantages, respectively. As a result, the external intercostals and the parasternal intercostals have an inspiratory function during breathing, whereas the internal interosseous intercostals and the triangularis sterni have an expiratory function.

Asunto(s)

RESUMEN

Retrograde transport of horseradish peroxidase, applied to cut peripheral nerves, was used to determine the rostrocaudal distribution of motoneurones supplying different branches of the ventral ramus for a single mid- or caudal thoracic segment in the cat. The motoneurones occupied a length of spinal cord equal to the segmental length but displaced rostrally from the segment as defined by the dorsal roots, with the number of motoneurones per unit length of cord higher in the rostral part of a segment (close to the entry of the most rostral dorsal root) than in the caudal part. The cross-sectional area of the ventral horn showed a rostrocaudal variation that closely paralleled the motoneurone distribution. The ratio between the number of motoneurones per unit length in the caudal and rostral regions of a segment (0.70) was similar to the ratio previously reported for the strength of functional projections of expiratory bulbospinal neurones (0.63). This is consistent with the motoneurones being the main targets of the bulbospinal neurones.

Asunto(s)

RESUMEN

Nucleus retroambiguus (NRA) consists of a column of neurons in the caudal medulla with crossed descending axons that terminate in almost all spinal segments. Many of these neurons transmit the drive for expiratory movements to the spinal cord. The same neurons are also known to participate, however, in other motor acts, such as vomiting and abdominal straining, for which it appears that the medullary circuits controlling the respiratory pattern are reconfigured. Plasticity in projections from the NRA to hindlimb motor nuclei provides evidence that some of these projections are involved in yet another motor act, female receptive behavior. Here, we present the hypothesis that the medullary circuits are also reconfigured to act as a central pattern generator for this behavior. In addition, we suggest that during estrus, plasticity is shown not only in spinal cord connections, but also in a selected membrane property of hindlimb motoneurons.

Asunto(s)

RESUMEN

In the macaque monkey and in humans, the monosynaptic cortico-motoneuronal system is well developed. It allows the cortical motor areas to make an important direct contribution to the pattern of muscle activity during upper limb movements. There is, in addition, good anatomical evidence for descending corticospinal inputs being able to influence the premotoneuronal networks of the cervical spinal cord, and especially those operating at the segmental level of upper limb motoneurons. While oligosynaptic inhibition has been easy to demonstrate in the macaque, and may be a very important component of descending corticospinal control, it has proved much more difficult to detect signs of oligosynaptic excitation. In contrast, in the squirrel monkey, in which the cortico-motoneuronal system is far less developed, oligosynaptic excitation is prominent. There are important changes in the interplay between direct and indirect pathways in different primates, which may provide important clues on the nature of the corticospinal control of upper limb function.

Asunto(s)

RESUMEN

There are conflicting views on the functional importance of the system of C3-C4 propriospinal neurones in the macaque, although the two sets of observations from the opposing laboratories are actually quite similar, both making the system appear much weaker than its well-known equivalent in the cat. One group asserts, mainly via evidence derived from experiments with strychnine, that this is a consequence simply of inhibition of the propriospinal neurone. However, we ague here that this judgement is premature and that much more needs to be known about the neurones involved and their connectivity before the analogy with the system in the cat is safe. This is particularly important because of a similar analogy which has been made with respect to measurements in human subjects.

Asunto(s)