Dorsolateral Fascicle Research Articles

Primary afferent origin of substance P‐containing axons in the superficial dorsal horn of the rat spinal cord: Depletion, regeneration and replenishment of presumed nociceptive central terminals

Substance P-like immunoreactivity (SPLI) was localized in the superficial spinal dorsal horn of the rat by means of light and electron microscopic immunocytochemical techniques. Serial immunocytochemical sections were subjected to densitometric measurements with an electronic Image Analyser, and with aid of a computer program, a two-dimensional reconstruction of the fine neuroanatomical structure of the SPLI-active regions of the lumbosacral upper superficial spinal dorsal horn was obtained. SPLI activity in the superficial dorsal horn outlines four well-marked and distinctly differing regions, called, in the mediolateral sequence, areas A, B, C, and D, plus Cajal's noyeau interstitiel ("lateral spinal nucleus" = "nucleus of the dorsolateral fascicle," L). Lumbosacral dorsal rhizotomy results in an almost complete depletion of SPLI from ipsilateral areas A, B, C, and D; it induces decreased SPLI in the area of the lateral spinal nucleus (L), ipsi- or contralaterally in an alternating fashion. Transection of the segmentally related, ipsilateral peripheral nerve induces a marked depletion of SPLI from areas A, B, and C but only a slight decrease in area D and virtually none in the area of L. Whereas a simple crush of the peripheral nerve (axocompression) induces only a slight depletion of SPLI, if any, semiautomatic densitometric analysis of serial immunocytochemical sections proves that a controlled crush injury (axocontusion) results in depletion of SPLI from the upper dorsal horn, similar to transection of the peripheral nerve. Following regeneration of the ipsilateral, segmentally related peripheral nerve, the original immunocytochemical structure of the superficial dorsal horn is re-established by SPLI-positive axonal sprouts originating from previously damaged dorsal root axons.

Postsynaptic dorsal column neurons in the cat: a study with retrograde transport of horseradish peroxidase.

The numbers, laminar position, perikaryal and dendritic morphology, and axonal trajectories of postsynaptic cells ascending the dorsal column have been studied after implantation of HRP pellets in either the dorsal columns or dorsal column nuclei after destruction of the dorsolateral fascicle on one side. Observations made throughout the spinal cord gave estimated figures of 800-1000 and 1700-2000 cells in lumbosarcal and brachial enlargements respectively on the side of the implant. The commonest type (C), centred on lamina IV, had dendritic trees greatly extended rostrocaudally and restricted mediolaterally in the lateral dorsal horn, the extension and restriction diminishing for more medial cells. Type B cells differed dramatically, with large straight dendrites in the transverse plane and large perikarya in medial lamina V. Type A cells, distinguished by both rostrocaudal and mediolateral restriction in dendritic trees, were only found medially in laminae III and IV. Outside the enlargements, in high lumbar and thoracic cord, many fewer cells were found, corresponding to Type C but with dendrites much elongated rostrocaudally and little mediolateral variation. Many small fusiform cells were found in medial lamina VI in the upper cervical cord, distinct from any of the above. A few cells were found in the cord enlargements in lamina VII of the contralateral ventral horn, with axons crossing through the ventral commissure. The axons of all cell types were tortuous, and some entered the dorsolateral fascicle before crossing into the dorsal column: collaterals were often seen but could not be followed far. A complementary study of cells with axons ascending in the dorsolateral fascicle is reported in the following paper.

Spinocervical neurons and dorsal horn neurons projecting to the dorsal column nuclei through the dorsolateral fascicle: a retrograde HRP study in the cat.

Spinocervical cells were identified by retrograde labelling from implants of HRP in the dorsolateral fascicle after destruction of the dorsal columns. They lay in laminae III and IV throughout the cord in estimated numbers of 700, 450 and 1100 in lumbosacral enlargement, upper lumbar and thoracic cord, and brachial enlargement respectively. In the cord enlargements dendritic trees were mainly or exclusively developed dorsally, with rostrocaudal exceeding mediolateral spread, and a gradient across the dorsal horn, lateral cells showing this contrast most strongly. Dendritic spread was limited at the II/III laminar boundary. Transition occurred at the edge of the enlargements to a shape with extreme rostrocaudal elongation of perikarya and of dendritic trees in upper lumbar and thoracic segments. Axons of spinocervical cells ascended in the most dorsal part of the fascicle, distinguishable from the larger spinocerebellar bundle lying adjacent and ventral. The initial axonal course was tortuous, with local collateral branching, the axon sometimes travelling briefly in the dorsal column. In other experiments implants were made ipsilaterally in the dorsal column nuclei after destruction of the dorsal columns. Cells were few and relatively poorly labelled, for which the reasons are discussed. Some such cells, lying in lamina IV, were similar to spinocervical tract cells and may have projected to both lateral cervical and dorsal column nuclei. Others, at the extreme lateral edge of the mid-dorsal horn, were quite different, with dendrites greatly extended rostrocaudally and primary and higher order dendrites projecting ventrally from the perikaryon.

Axonal growth cones in the developing amphibian spinal cord.

Axonal growth cones in the spinal cord of embryonic and larval Xenopus (stages 24-48) were filled with the anatomical tracer horseradish peroxidase (HRP). Growth cones of lateral and ventral marginal zones, including those of descending spinal and supraspinal pathways, were labeled by application of tracer to the caudal medulla or to one of several levels of the spinal cord. Central axons of sensory neurons were filled via their peripheral processes. Growth cone configuration varied widely but fell into five general categories: complex with both filopodia and veils, filopodia only, lamellipodia only, clavate, and fusiform. Several general patterns emerged from the distribution of these various configurations. Growth cones of younger animals generally were more complex than those of older ones. Growth cones closer to the leading edge of descending fiber bundles were more elaborate than those that followed. Growth cones of the dorsolateral fascicle, which carries ascending central processes of Rohon-Beard and sensory ganglion neurons, were very simple and followed a straight course rostrally, whereas those of descending axons of the lateral fiber areas were more complex and sometimes spread over almost the entire lateral marginal zone. Growth cones of Rohon-Beard central ascending axons were fusiform or clavate, while those of sensory ganglion axons showed several fine filopodia at their tips. Growth cones of both types of sensory axons change configuration as they approached the hindbrain, becoming more complex. This study demonstrates that the configurations of growth cones belonging to the same axonal pathway vary with age and with position along their routes, and that growth cones of different neuron classes exhibit characteristic ranges of morphological variation.

Dorsolateral spinal afferents to some medullary sensory nuclei. An anatomical study in the cat.

The course and termination of afferents in the spinal dorsolateral fascicle to some medullary sensory nuclei were studied by tracing degeneration following lesions of spinal white matter. The main conclusions depend on successive degeneration experiments; other points were studied with single-stage lesions. The dorsal column nuclei were particularly studied; terminations in these nuclei following dorsolateral lesions followed a clear-cut pattern, with fibres arising from segments below T6 terminating in the gracile nucleus and those with more rostral origin solely in the cuneate nucleus. In both nuclei, the major terminations were in their rostral third with most fibres traversing deep caudal regions where some termination also occurred. Some fibres ended contralaterally. These restricted regions of termination contrasted with the wide-spread terminations seen after lesions of the dorsal column. A region at the cuneate rostral pole, adjacent to but clearly separable from nucleus z, receives a dense projection from both caudal and rostral spinal levels, the former fibres terminating in the dorsal part of the region, the latter extending more ventrally. We treat this as a separate subnucleus. The afferents to the dorsal column (together with those terminating in the other nuclei studied) were confined to the extreme dorsolateral white matter. Our observations confirm the established view that only afferents arising from caudal segments (below at least T 4-5) terminate in nucleus z, and that afferents terminating in group x arise from all levels (at least between C5 and L5): also that neither receives any afferents through the dorsal columns. Dorsolateral fibres arising from segments above at least T6 terminate in a clear-cut area at the lateral border of the external cuneate nucleus. Heavy terminal degeneration was also seen in the lateral cervical nucleus of afferents arising from both above and below T 4-5.

Input from ipsilateral proprio- and exteroceptive hind limb afferents to nucleus Z of the cat medulla oblongata.

1. Extracellular recordings have been made from proprio- and exteroceptive neurones in nucleus Z of the cat medulla oblongata. 2. Seventeen non-relay cells were excited by ipsilateral hind limb group I muscle afferents. Their functional were similar to those of the corresponding relay cells (Johansson & Silfvenius, 1977), i.e. activation by axon-collaterals of dorsolateral fascicle (DLF) fibres was observed, indicative of an input from the dorsal spinocerebellar tract (DSCT) to these neurones. The non-relay cells differed, however, from the relay cells in that a larger proportion of them were disynaptically connected to the spinal fibres. It is suggested that the non-relay cells by inhibition modulate the group I relay transmission in nucleus Z. 3. Fifteen cells were excited by ipsilateral hind limb low threshold skin afferents with their spinal fibres at the first cervical segment located either in the DLF or in the dorsal column (DC). Evidence for a cutaneous hind limb bulbothalamic path independent of that of the DC and of the spinocervicolemniscal path is presented. 4. Six cells were activated by ipsilateral hind limb joint afferents at low threshold. At the C1 level the spinal fibres were located either in the DLF or in the DC. No joint activated relay-cells were encountered. Axon-collateral activation of DLF-linked joint cells was observed during cerebellar stimulation, indicating that segmental DSCT cells mediated the joint input to nucleus Z. 5. The topographical organization within nucleus Z and its input relation to the DSCT is discussed.

Connexions from large, ipsilateral hind limb muscle and skin afferents to the rostral main cuneate nucleus and to the nucleus X region in the cat.

1. Evidence is presented for an input from ipsilateral hind limb group I muscle afferents and low threshold cutaneous afferents, to cells in the rostral division of the main cuneate nucleus (rMCN) and in the region of the descending vestibular nucleus and the nucleus X of Brodal & Pompeiano (1957a), the (DV-X). 2. Thirteen group I-rMCN cells were recorded from. The functional properties of these cells were similar to those of nueleus Z (Landgren & Silfvenius, 1971; Johansson & Silfvenius, 1977a, b). The cells were monosynaptically linked to spinal dorsolateral fascicle (DLF) fibres. Nine cells projected to the contralateral thalamus, i.e. a second group I hind limb bulbothalamic tract is described. Ten cells were synaptically activated from the ipsilateral cerebellum from the anterior projection zone of the dorsal spinocerebellar tract (DSCT). Axon-collateral activation by DSCT fibres was established for two of these cells. They were both bulbothalamic relay cells. For the remaining eight cells, activated from the cerebellum, this was not proven. These cells could, however, either be linked to DSCT fibres or to short axon-collaterals of a cell body of unknown location. A projection from the rMCN to the cerebellum is described and agrees with recent anatomical findings. Two cells were not excited from the cerebellum. 3. Four rMCN cells were activated by cutaneous afferents with their secondary axons in the DLF. Suggestive evidence for a bulbothalamic cutaneous hind limb path via the rMCN is presented. Two cells were activated from the cerebellum, presumably via axon-collaterals of nonsegmental cells. 4. Eight group I-DV-X cells were recorded from. They were monosynaptically linked to spinal DLF fibres and resembled functionally the nucleus Z and rMCN cells when stimulated from the periphery. Two cells projected to the contralateral thalamus, and two others were synaptically excited. Seven cells were activated from the ipsilateral cerebellum. Two of them projected to the cerebellum, and three were synapitcally activated by axon-collaterals of an undefined non-segmental cell. 5. Two DV-X cells which were activated by cutaneous afferents possibly had their spinal fibres deep in the dorsal column. Both were activated from the cerebellum, one by collaterals of a spinal axon. The functional organization of the three juxtaposed medullary nuclei, Z, rMCN and DV-X is discussed.

Axon-collateral activation by dorsal spinocerebellar tract fibres of group I relay cells of nucleus Z in the cat medulla oblongata.

1. The problem whether the group I hind limb cerebral tract and the dorsal spinocerebellar tract (DSCT) have common spinal axons has been investigated in the present study. 2. Thirty-two cells located in the nucleus Z of the cat medulla oblongata and activated by spinal fibres in the dorsolateral fascicle were selected for the study. 3. Extracellular recording from these neurones demonstrated that most of them were monosynaptically linked to spinal fibres excited by ipsilateral hind limb group I muscle afferents. The cells exhibited a restricted spatial convergence and had a limited excitatory convergence from group II muscle and from skin afferents. 4. Antidromic activation from the contralateral thalamus showed that they were bulbothalamic relay cells. 5. Cerebellar surface or depth stimulation activated 88% of the twenty-six cells tested at a short latency. With a collision technique it was demonstrated that twelve out of twenty-three (52%) of these group I relay neurones were activated by axon-collaterals of the DSCT. 6. 43% of the cells activated from the cerebellum, but not proven to be linked to the DSCT, could, nevertheless, have been excited by DSCT axon-collaterals, if it is assumed that different fibres converging with excitation on the group I relay cells were activated in the collision test.

Projections to the cat's cerebral cortex from low threshold joint afferents.

AbstractThe projections to the cerebral cortex from the contralateral low threshold afferents of the musculocutaneous branch to the elbow joint (Ejt) and the posterior knee joint nerve (Kjt) were investigated in cats anesthetized with chloralose. Graded electrical stimulation of the nerves was used to evoke the cortical potentials. Three discrete joint projection areas were found in the cytoarchitectonic area 3 of the posterior sigmoid gyrus, i.e. one Ejt and two Kjt loci. These loci overlapped with the projections from group I muscle afferents. One Ejt and one or two Kjt loci were observed in positions corresponding to cytoarchitectonic areas 1 and 2. They did not receive input from group I muscle afferents. A separate locus with overlap between forelimb joint and muscle afferents was located in area 4 y. Components 1 and II of the joint nerve volley evoked short latency potentials in all cortical loci. Low threshold cutaneous afferents evoked responses in all joint loci. The spinal course of the ascending Ejt path was mainly located in the dorsal column. Kjt component I afferents travelled mainly in the dorsal columns and component I and II afferents in the dorsolateral fascicle. The Kjt path in the dorsolateral fascicle ascended uncrossed to the level of Ci.

Some properties of spinal connections of the cat's dorsal column nuclei which do not involve the dorsal columns

After total division of the dorsal columns at C4, both excitatory and inhibitory actions were produced in the gracile and in the cuneate nucleus, by electrical stimulation of the ipsilateral dorsolateral fascicle caudal to the section, and by mechanical stimulation of peripheral sstructures. Most observations were made in the rostral 5 mm of the nuclei. Stimulating the DLF produced direct responses of single fibres, and also postsynaptic responses in cells, in these nuclei. Postsynaptic responses were seen in 220 single units: 30% (out of 157 tested) were relay cells responding antidromically to stimulation in the contralateral upper brain stem, and some 40% of these cells were shown to have receptive fields, mostly sensitive cutaneous fields, on the appropriate ipsilateral limb. Some cells responding postsynaptically, for which there no evidence of lemniscal projection, responded only to noxious peripheral stimulation of one or more ipsilateral or contralateral paws, and it is suggested these may be inhibitory interneurones. Many cells in these nuclei could be inhibited by noxious peripheral stimulation from a wide and often bilateral field. Stimulating the ipsilateral DLF after dorsal column section inhibited the postsynaptic field potential (N-wave) in these nuclei, and it was shown by testing terminal excitability in dorsal column axons above the section that part at least of this inhibition was presynaptic. These results show that the dorsal column nuclei are associated in a complex way with sensory mechanisms in the dorsal part of the cord other than the dorsal columns,a fact which calls for re-evaluation of certain earlier experimental work.

Nucleus Z, the medullary relay in the projection path to the cerebral cortex of group I muscle afferents from the cat's hind limb.

1. The medullary relay of hind limb muscle afferents was studied in cats anaesthetized with chloralose. Evoked potentials were recorded from the dorsal surface of the medulla oblongata and from the depth of the medulla with penetrating micro-electrodes. Graded electrical stimulation of the muscle nerves was used. The afferent volley was monitored by recordings from the lumbar dorsal roots or from the peripheral nerves.2. Group I muscle afferents from the ipsilateral quadriceps, posterior biceps-semitendinosus and gastrocnemius-soleus nerves evoked potentials in the nucleus Z of Brodal & Pompeiano (1957a). Focal and unitary potentials were recorded within 2.7-3.8 mm rostral to the obex and 2.8-4.1 mm lateral to the mid line. The recording positions were checked histologically.3. Focal and unitary responses appeared at threshold strengths of the afferent volleys. The latencies of the focal potentials varied between 4.5 and 7.0 msec, those of the unitary ones between 5.1 and 11.0 msec. Group II muscle afferents and low threshold cutaneous afferents also projected to nucleus Z.4. An antidromic discharge was evoked in the relay cells of nucleus Z by electrical stimulation of the contralateral thalamus.5. A lesion of nucleus Z abolished the response evoked in the contralateral post-sigmoid gyrus of the cerebral cortex by the Group I muscle afferents of the hind limb.6. A superficial transection of the ipsilateral dorsolateral fascicle at the 1st cervical segment abolished the potentials evoked in nucleus Z.7. Results of lumbar cord transections showed that most of the primary afferents of the Group I hind limb path supplying nucleus Z enter the dorsolateral fascicle at L3 level.8. The relation of the Group I hind limb path to the dorsal spinocerebellar tract is discussed.

Projection to cerebral cortex of group I muscle afferents from the cat's hind limb.

1. Muscle afferent projections from the contralateral hind limb to the postsigmoid gyrus of the cerebral cortex were investigated in cats anaesthetized with chloralose. The evoked potentials were recorded from the cortical surface or from deeper layers by penetrating micro-electrodes. Graded electrical stimulation of the nerves was used.2. Group Ia as well as Ib muscle afferents from the contralateral quadriceps, posterior biceps-semitendinosus, gastrocnemius-soleus and deep peroneal muscles projected to two different loci in the postsigmoid gyrus. One of these was located on the dorsal surface of the hemisphere 4-5 mm lateral to the mid line and 1-3 mm posterior to the cruciate sulcus, thus rostro-medial to the postcruciate dimple. The other was located on the medial surface of the hemisphere adjacent to the cruciate sulcus. There was no overlap between the two loci.3. There was no significant difference in thresholds or latencies of the Group I responses in the two loci. The latency was short and similar to that of the potential evoked by the cutaneous afferents in the somatosensory primary projection areas.4. The Group Ib path was largely independent of the Ia path, because a maximal Group I volley evoked a response, when the Ia path was made refractory by simultaneous stimulation with a maximal Ia volley at 20 per second.5. The cortical potentials evoked by the Group I muscle afferents from the contralateral hind limb did not change after transection of the dorsal columns at C1-C3 levels but disappeared after a superficial section in the dorsolateral fascicle at C1 level. The responses were not affected by cerebellectomy. It was concluded that the path travelled with the dorsal spinocerebellar tract or utilized brain stem collaterals of this tract.6. Group II muscle afferents evoked a response near the border of the Group I loci, but not in the positions where the Group I responses were maximal in amplitude.7. The receptor origin of the stimulated Group I afferents, the location of the medullary relay in the Group I path and the destination of the efferent outflow from the Group I loci were discussed.