Collateral sprouting of the central terminals of cutaneous primary afferent neurons in the rat spinal cord: Pattern, morphology, and influence of targets (original) (raw)
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The Journal of Comparative Neurology, 1994
In order to establish the specificity of growth and termination of dorsal root afferents within the developing spinal cord, the central dorsal horn terminals of myelinated sensory afferents were labelled at various stages in the rat from embryonic day (E)18 through to postnatal day (P) 35 using horseradish peroxidase conjugated to choleragenoid (B-HRP). The preferential labelling of A fibre afferents with this tracer was found to be as clear in the neonate as has been reported for the adult. The results show that while the somatotopic arrangement of A fibre afferent terminals in the dorsal horn is established early in development, the laminar projections are not. Following peripheral nerve or local skin injections of B-HRP, A fibre terminals were found to project throughout laminae I to V, including lamina I1 (substantia gelatinosa). This widespread termination was observed consistently until the end of the third postnatal week. After P22 the terminal field becomes restricted to the normal laminae I11 to v. D
Prenatal development of rat primary afferent fibers: I. Peripheral projection
The Journal of Comparative Neurology, 1995
Development of the peripheral innervation patterns of the Ll-S1 lumbosacral ganglia and motor segments in embryonic day 12-17 (E12-17) rat embryos was examined using carbocyanine dyes. Individual dorsal root ganglia (DRGs) and/or isolated ventral horn (VH) segments, or individual peripheral nerves, were isolated in rat embryos fixed at different stages and filled with one of three carbocyanine dyes; DiI, DiA, and DiO. Individual experimental preparations included labeling of 1) single DRGs; 2) multiple DRGs with alternating dyes, DiO, DiI, and DiA; 3) single isolated VH segments; 4) multiple VH segments with alternating dyes; 5) single VH segments and the corresponding segmental DRGs with different dyes; and 6) two or more individual peripheral nerves labeled with different dyes.
European Journal of Neuroscience, 1994
Previous studies have shown that following neonatal peripheral nerve injury, adjacent intact myelinated and unmyelinated primary afferents sprout into the central denervated terminal area. The present study investigates this in more detail and goes further, to study the fate of the central terminals of the surviving axotomized primary afferent neurons. Bulk labelling of the sciatic and saphenous nerves with horseradish peroxidase conjugated to choleragenoid (B -HRP), to label the A fibres, or wheatgerm agglutinin (WGA-HRP), to label C fibres were employed to investigate the central consequences of sciatic nerve section and ligation on the day of birth, in adult rats. Bulk labelling of the axotomized sciatic or intact saphenous nerve with either tracer and comparison with contralateral controls revealed alterations to the terminal field. The intact saphenous nerve terminal field expanded caudally from mid L4 to the L4-L5 boundary when labelled with WGA-HRP and to the sacral cord when labelled with B -HRP. Labelling the axotomized sciatic nerve with either tracer revealed little change in the overall somatotopic organization of central terminals, although labelling was less intense compared to control nerves and more variable with WGA -HRP. Invasion of the substantia gelatinosa (SG) by axotomized A fibres was observed in segments L3 -5, into the area occupied by axotomized C fibres. This area was also invaded by intact saphenous A fibres in the L4 -5 segments. These results demonstrate that following neonatal nerve section: (i) axotomized primary afferents are able to retain a 'normal' somatotopic map in the rostrocaudal plane; (ii) both A and C fibres from adjacent intact nerves sprout into the denervated territory, but A fibres sprout further caudally; (iii) axotomized A fibres and invading intact A fibres both sprout dorsally into denervated SG. As a result, there is considerable overlap between nerve territories in denervated spinal cord, suggesting that competition for laminar termination sites exists between A and C fibres and also between axotomized and intact primary afferents.
Developmental Brain Research, 1988
Sciatic nerve section and ligation on the day of birth results in marked growth retardation of the rat dorsal horn. This transneuronal effect was examined in spinal cord cells that project to the brain by retrograde labelling with HRP from contralateral dorso-and ventrolateral tracts in the thoracic white matter. HRP-impregnated gel pellets were implanted in the tracts for 48-72 h to allow intense somadendritic staining of the projection cells. The results show that cells in rats whose sciatic nerve has been sectioned at birth have a mean somal area that is 40% smaller than controls. Primary dendrites are reduced from a mean of 4.1 per cell to 3.1 per cell and secondary branching is reduced by 75%. The results suggest that there was no actual cell death, only growth retardation. An intact primary afferent input apparently has a strong transneuronal trophic influence on spinal cord sensory cells projecting to the brain.
The Journal of Comparative Neurology, 1993
In order to investigate the reorganization of the neuropil of the dorsal horn following peripheral nerve injury, the central terminal arborizations of 35 A beta primary afferent neurons, chronically injured by a cut and ligation of the sural nerve 6-12 weeks previously, were studied by the intra-axonal injection of horseradish peroxidase. Their morphology was compared to 13 intact sural nerve hair follicle afferents. Following axotomy, three kinds of morphological abnormalities were observed in the collateral arbors of the 26 afferents that were hair follicle-like. Atrophy with thin stem axons and reduced terminal branch patterns with few boutons was seen in 5 afferents. Sprouting of bouton-containing terminals into lamina I and 110 was found in 8 afferents. Finally, abnormal arborization patterns in the deeper laminae were observed in 29%) of the collateral arbors. Changes included the loss in some arbors of a flame-shaped appearance, which is characteristic of hair follicle afferents, atypical branching patterns and ventrally directed axons producing wider and deeper arbors, compared to normal.
European Journal of Neuroscience, 1991
The rostrocaudal distribution of saphenous nerve inputs into the lumbar dorsal horn from L2 to L6 has been investigated in urethane anaesthetized rats whose left sciatic nerve was cut and ligated at birth. In normal cord, electrical stimulation of the saphenous nerve evoked dorsal horn spikes in L2 to caudal L4. Few or no spikes were evoked in L5. After neonatal sciatic nerve section, saphenous nerve stimulation evoked spikes throughout segments L2 to L6. Dorsal horn cell receptive fields were also altered following neonatal sciatic nerve section. A somatotopic map of the lumbar enlargement in normal rats was constructed from the receptive fields (RFs) of adjacent dorsal horn cells. Cells with RFs in the saphenous skin region were concentrated in L3 and rostra1 L4 and very few were found in L5. After neonatal sciatic nerve section, however, a substantial number of cells with low threshold saphenous skin RFs were also found in caudal L4 and throughout L5. These results show that the central saphenous nerve terminal sprouts that grow into the sciatic terminal region following neonatal sciatic nerve section , J. Comp. Neurol., 240, 414-422; Fitzgerald et a/., 1990, J. Comp. Neurol., 300, 370 -385) form functional connections. This results in dorsal horn cells that are not normally influenced by saphenous nerve inputs developing substantial low threshold RFs in saphenous nerve skin regions.
Brain Research, 1986
The anterograde transport of wheat germ agglutinin-horseradish peroxidase conjugate was used to study the normal distribution of sensory nerve axons in the plantar skin of the rat hindlimb and at various times after chronic sciatic nerve injury in adult and neonatal rats. In adults, thin saphenous nerve axons were found in a small area laterally to the normal saphenous nerve territory 2-24 weeks after sciatic nerve lesion. In neonatal rats, at 6 and 10 weeks after sciatic nerve injury thin saphenous nerve axons were found almost or all over the sole of the foot, respectively, and in all 5 toes. At longer survival times, the area innervated by saphenous nerve axons became smaller. However, this area was now occupied by thin, as well as coarse axons. When adult animals were subjected to saphenous nerve crush simultaneously with the sciatic nerve lesion, thin, as well as coarse, nerve axons were found laterally to the normal saphenous nerve territory. The findings indicate that thin cutaneous sensory axons of adult mammals can extend collateral sprouts in glabrous skin for a short distance. This capacity appears to be greater in neonatally lesioned animals, where it is present for coarse cutaneous sensory axons as well. However, after neonatal nerve injury collateral sprouts seem to disappear from the initially most distally reinnervated area. Regenerating sensory axons in adult rats seem to have a greater capacity for collateral sprouting than intact axons. Coarse and thin cutaneous sensory axons could be found in this instance. In all instances a great part of the plantar skin remained denervated, suggesting that there is an upper limit for the territory which can be maintained by cutaneous sensory neurons reinnervating glabrous skin.
Maintenance of specificity by sprouting and regenerating peripheral nerves. I. Normal variability
Brain Research, 1987
Inter-animal variability in the spinal representation of a single hindlimb muscle, tibialis anterior (TA), in the cat, was examined by (1) retrograde transport of intramuscularly injected HRP, (2) dissection of the lumbosacral plexus and (3) reflex testing after acute section of spinal nerves L 5, L6, S l and S2 sparing L 7. No variability between the two sides of the same animal was seen. The transverse position of the TA motor nucleus and the number of labeled cells was constant between the two sides in each animal. Inter-animal variability was considerable, however, in that the number of motor neurons and rostrocaudal extent of the motor neuron column supplying TA varied considerably from animal to animal. According to the relationship between the position of the lumbosacral plexus and the distribution of spinal nerves, 3 classes of representation of the plexus were found: prefixed, postfixed and intermediate. In animals in which the lumbosacral plexus was prefixed, more than one half of labeled cells were rostral to the L 7 segment; in those with postfixed plexus more than half the cells were caudal to L 7. Section of L 5, L 6, S 1 and S 2 spinal nerves weakened the tibialis anterior tendon reflex in 'prefixed plexus' animals but abolished that reflex in 'postfixed' plexus animals, in spite of the presence of labeled motor neurons projecting through the spared L 7 nerve. This suggests that some of the afferents and efferents comprising the TA tendon reflex may travel in different spinal roots or that a particular distribution of motor axons within a muscle is required for the maintenance of this particular reflex activity.
Developmental Brain Research, 1999
To study the reorganization of the primary afferent input in the spinal dorsal horn during post-natal development, synaptic responses Ž . evoked by large Ab and fine Ad afferents were recorded from substantia gelatinosa SG neurons in slices obtained from immature Ž . Ž . Ž . post-natal days 21-23 and mature rats post-natal days 56-60 . Threshold stimulus intensities and conduction velocities CVs of Ab Ž . and Ad afferents were determined by intracellular recordings of the antidromic action potentials from dorsal root ganglion DRG neurons Ž . isolated from immature and mature rats. In immature rats, excitatory postsynaptic currents EPSCs were elicited by stimulation sufficient Ž . to activate Ab afferents in the majority of SG neurons 64.9%, 24 of 37 neurons , while most EPSCs observed in mature rats were Ž . elicited by stimulation of Ad afferents 62.5%, 25 of 40 neurons . These observations suggest that the primary afferents innervating SG neurons were reorganized following maturation; Ab afferents were the predominant inputs to the SG neurons in the immature state, thereafter Ad afferents were substituted for the Ab afferents to convey sensory information to the SG neurons. This relatively slow reorganization of the sensory circuitry may correlate with slow maturation of the SG neurons and with a delay in the functional connections of C afferents to the SG neurons. q
Developmental Biology, 1998
Axonal interactions, which are mediated by cell adhesion molecules (CAMs) as well as other types of membrane proteins, are important for sensory axon pathfinding in the developing chick hindlimb. We have previously shown that injection of antibodies that block the function of either G4/L1 or N-cadherin into the limb, starting when the first sensory axons reach the plexus, alters the segmental pattern of projections along cutaneous nerves. Specific removal of polysialic acid from NCAM using the enzyme endoneuraminidase N (Endo N) also resulted in significant changes in cutaneous projection patterns, while injection of antibodies against NCAM itself had no obvious effect (M. G. Honig and U. S. Rutishauser, 1996, Dev. Biol. 175, 325-337). To help understand the cellular basis for these findings, we developed a tissue culture system in which the axons from dorsal root ganglion explants grow within defined laminin lanes and examined whether the same treatments increased or decreased a growth cone's tendency to be closely associated with neighboring axons. After 2 days in culture, images of the cultures were recorded, antibodies or Endo N was added, and images of the same fields were recaptured an hour later. To quantify the results, growth cones located in defined regions of the laminin lanes were classified, before and after the perturbation, as "free" (i.e., growing primarily on the laminin substratum), "fasciculated" (i.e., growing tightly along other neurites), or "intermediate" (i.e., growing both on the laminin substratum and in contact with other neurites). We found that anti-G4/L1 and anti-N-cadherin, but not anti-NCAM, caused an increase in defasciculated growth cones, whereas Endo N resulted in an increase in fasciculated growth cones. These changes in fasciculation are consistent with the changes in cutaneous projections seen in our previous in ovo perturbations. The results from these tissue culture experiments thus provide strong support for the idea that one mechanism by which CAMs affect sensory axon pathfinding in vivo is by regulating the affinity of sensory growth cones for neighboring axons, which in turn can modulate the growth cone's ability to navigate through the surrounding environment.