The cat model of spinal injury.
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Biomedical subjects
Publications and source records attributed to H Leblond.
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In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.
Interneuronal convergence of corticospinal and segmental pathways involved with the generation of extensor activities during locomotion was investigated in decerebrate and partially spinalized cats. L-dihydroxyphenylalanine (L-DOPA) was slowly injected until long-latency, long-lasting discharges could be evoked by the stimulation of contralateral flexor reflex afferents (coFRA) and the group I autogenetic inhibition was reversed to polysynaptic excitation in extensor motoneurons. Under these conditions, we stimulated in alternation the contralateral pyramidal tract (PT), group I afferents from knee and ankle extensor muscles, and both stimuli together. We did the same for the stimulation of PT and of coFRA. Clear polysynaptic EPSPs could be evoked from all three sources in 32 extensor motoneurons. Convergence was inferred from spatial facilitation, which occurred when the amplitude of the EPSPs evoked by the combined stimuli was notably larger than the algebraic sum of the EPSPs evoked by individual stimulation. Spatial facilitation was found between PT and extensor group I inputs in 30/59 tests (51%) in 20 motoneurons and in all cases (6/6) between PT and coFRA in six motoneurons. When fictive locomotion was induced with further injection of L-DOPA, PT descending volleys from the same stimulating site could reset the stepping rhythm by initiating bursts of activity in all extensors. These results indicate that at least some of the corticospinal fibers project onto interneurons shared by the coFRA and the polysynaptic excitatory group I pathways to extensors. The implications of such convergence patterns on the organization of the extensor "half-center" for locomotion are discussed.
Intracellular recording of lumbosacral motoneurones in the decerebrate and partially spinalized cat injected with nialamide and L-dihydroxyphenylalanine (l-DOPA) was used to investigate the interneuronal convergence of two bulbospinal pathways and of the segmental pathways involved with the generation of extensor activities during locomotion. Deiter's nucleus (DN) or the medial longitudinal fasciculus (MLF) was stimulated in alternation with, and in combination with, stimulation of group I afferents from extensor muscles or of contralateral flexor reflex afferents (coFRA). The evoked polysynaptic EPSPs were recorded in extensor motoneurones when long-latency, long-lasting discharges were evoked by the stimulation of coFRA and when the group I autogenetic inhibition in extensors was reversed to polysynaptic excitation. Spatial facilitation was inferred when the amplitude of the EPSPs evoked by the combined stimuli was notably larger than the algebraic sum of the EPSPs evoked by individual stimulation. Both DN (16 motoneurones) and MLF inputs (8 motoneurones) showed spatial facilitation when preceded by coFRA stimuli and both could reset the rhythm of fictive stepping by triggering a precocious extensor phase. MLF showed spatial facilitation with extensor group I inputs in 69% of trials but DN failed to show spatial facilitation in any cells. These results indicate that DN and MLF project to the coFRA pathways of the extensor half-centre for locomotion and MLF, but not DN, converge on segmental interneurones of the extensor group I pathways. The implications of such convergence patterns on the functional organization of the extensor half-centre are discussed.
The aim of this study is to understand the functional organization of presynaptic inhibition in muscle primary afferents during locomotion. Primary afferent depolarization (PAD) associated with presynaptic inhibition was recorded intra-axonally in identified afferents from various hindlimb muscles in L6-L7 spinal segments during fictive locomotion in the decerebrate cat. PADs were evoked by the stimulation of peripheral muscle nerves and were averaged in the different epochs of the fictive step cycle. Fifty-three trials recorded from 39 muscle axons (37 from group I and two from group II) were retained for analysis. The results showed that there was a significant phase-dependent modulation of PAD amplitude (p < 0.05) in a majority of muscle afferents (30 of 39, 77%). However, not all stimulated nerves led to significantly modulated PADs in a given axon (36 of 53 trials, 68%). We also observed that the pattern of modulation (phase for maximum and minimum PAD amplitude and the depth of modulation) varied with each recorded afferent, as well as with each stimulated nerve. We further evaluated the effect of PAD modulation on the phasic transmission of the monosynaptic reflex (MSR) and found that PADs decreased the MSR amplitude in all phases of the fictive step cycle, independent of the PAD pattern in individual group I fibers. We conclude that (1) PAD modulation patterns of all group I fibers contacting motoneurons led to an overall reduction in monosynaptic transmission, and (2) individual PAD patterns could participate in the control of transmission in specific reflex pathways during locomotion.
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We have quantified the number and size of myelinated fibers of the ventral and dorsal roots of selected segments that innervate the forelimbs (C8) and hindlimbs (L4) in the developing opossum, Monodelphis domestica. The gray opossum was chosen because it is born very immature and its somatomotor development occurs almost entirely postnatally. After aldehyde fixation, osmium postfixation, and resin embedding, the roots were cut transversely (1.5 pm), stained with toluidine blue, and observed and photographed by using light microscopy. The counts and measurements were made with a digitizing table. Myelination of the C8 and L4 roots begins during the second week of life and occurs according to two gradients: rostrocaudal and ventrodorsal. The number of myelinated fibers in these roots increased over approximately 7 weeks after which an excess, compared with their adult value, was recorded during the following weeks in three of the four roots. The supernumerary myelinated fibers are presumed to be collaterals. The fibers increased in diameter until at least 98 days. The classification according to size for the ventral roots (alpha and gamma) became evident in the fourth week, but that in types I, II, and III for the dorsal roots was never clear. There was no significant difference in the number and size distribution of myelinated fibers between sexes until late in development. The fibers innervating the limbs thus become myelinated postnatally in the opossum, a process that occurs over a protracted period and that continues after sensorimotor reflexes and locomotion appear adult-like.
The fine control of locomotion results from a complex interaction between descending signals from supraspinal structures and sensory feedback from the limbs. In this report, we studied the interaction between vestibulospinal volleys descending from Deiters' nucleus and group I afferent input from extensor muscles. It has been shown that both pathways can exert powerful control over the amplitude and the timing of muscle bursting activity in the different phases of the step cycle. The effects of stimulating these pathways on the fictive locomotor rhythm were compared in decerebrate, partially spinal cats (ipsilateral ventral quadrant intact) injected with nialamide and L-dopa. As reported before, stimulation of both Deiters' nucleus and group I fibres from ankle extensor muscles, when given during the flexor phase, stopped the flexor activity and initiated activity in extensors. When applied during the extensor phase, the same stimulation prolonged the extensor activity and therefore delayed the onset of flexor activity. This similarity suggests that the two pathways might converge on common spinal interneurones. This possibility was tested with the spatial facilitation technique in lumbosacral motoneurones. Deiters' nucleus and group I fibres from extensor muscles were stimulated with different intensities and with several different coupling intervals. Motoneurones showing clear di- and/or polysynaptic excitation from both pathways were retained for analysis. Surprisingly, in all cases, there were no signs of spatial facilitation, but a simple algebraic sum of the two excitatory postsynaptic potentials. This result indicates that each input acts on the rhythm generator through separate interneuronal pathways.
A quantitative light-microscopic analysis of the ventral and dorsal roots at the C8 and L4 segments of the spinal cord was made in the opossum, Monodelphis domestica, to evaluate the number of myelinated fibers and their class distribution, and will serve as a baseline to a study of myelinogenesis in that species. In male opossums, the C8 ventral root comprises an average of 595 myelinated fibers (70.3% alpha: 29.7% gamma) and the dorsal root 1,124 fibers (29.4% type I: 41.2% type II: 29.4% type III). The L4 ventral root has an average of 831 fibers (57.9% alpha: 42.1% gamma), and the dorsal root 2,079 fibers (17.4% type I:44.7 type II: 37.9% type III). The females have less fibers but their size and class proportions are comparable to those of the males. These data are discussed in relation to peripheral innervation and are compared to those reported for the rat and the cat.
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The case is considered of a young asthmatic girl with a number of food allergies. After therapy, her pulmonary condition improved and the number of food allergies also decreased.