Neurochemical transmission in the dorsal column nuclei

The transmitter chemistry of the dorsal column nuclei is reviewed, with special emphasis on the monosynaptic component of the dorsal column-medial lemniscal pathway. It is maintained that in this anatomically addressed system concerned mainly with fast, secure sensory transmission, amino acids represent the predominant mechanism used for chemical relay of primary afferent impulses. The major excitatory primary afferent transmitter is most likely glutamic acid, whereas gamma-aminobutyric acid (GABA) fulfills adequately the role of transmitter of recurrent, postsynaptic and presynaptic inhibition. Recent immunohistochemical and physiological evidence indicates that 5-hydroxytryptamine, originating mainly from neurons of the raphé nuclei, plays a modulatory role in dorsal column transmission of innocuous sensory information. The basic synaptic elements involved in transmission across this relay, along with their corresponding chemical identities, are presented in the form of a speculative model.     

Stimulation of dorsal column in multiple sclerosis.

The effect of stimulating the dorsal column in 19 selected patients with multiple sclerosis was studied in detail over two weeks. Before and during stimulation the patients were examined clinically; videotape recordings made of their movements; psychomotor performance tested; electrolaryngography performed; and urodynamic studies carried out. Improvement was seen in walking speed, power in certain muscle groups, chronic pain, and bladder function. The motor improvement was thought to be related to the effects of high motivation and practice, and therefore to be of doubtful importance. The changes in bladder function were more convincing and justify further study.     

Treatment of spasmodic torticollis by dorsal column stimulation.

A new method is described to treat spasmodic torticollis with the implantation of a dorsal column stimulator at the C1--2 level or with transcutaneous stimulation. 22 patients were evaluated. 3 had sufficient relief to be treated with transcutaneous stimulation only. An additional 6 patients had surgically implanted dorsal column stimulators. It was empirically determined that a frequency of 800--1,100 Hz gave the best relief from torticollis. 1 patient had an excellent result; 3 have had good results; 1 had a fair result, and 1 had a poor result. An additional patient with dystonia musculorum deformans was considerably improved by the use of dorsal column stimulation.     

Cortical modulation of dorsal column nuclei: A computational study

We present a computational study aimed at exploring the sensorimotor cortex modulation of the behaviour of dorsal column nuclei, specifically the impact of synaptic parameters, during both sleep and waking conditions. On the basis of the circuit proposed by Canedo et al. (2000), we have developed realistic computational models that have been tested with simultaneous electrocorticographic as well as intracellular cuneate recordings performed in anaesthetized cats. The results show that, (1) under sleep conditions, the model can block the transmission of afferent sensory information and, (2) operations expected during wakefulness, such as filtering and facilitation, can be performed if synaptic parameters are appropriately tuned. Action Editor: Steve Redman     

Effect of dorsal column stimulation on pain-induced intracerebral impulse patterns.

Evoked electrical potentials were recorded via intracerebral electrodes in a patient with stump and phantom limb pain who had a previously implanted dorsal column stimulator. When pain was elicited by peripheral stimulation it was found that positive deflections appeared in the ventrolateral nucleus of the thalamus at time latencies corresponding to the propagation velocities of A delta- and C-fibres. Dorsal column stimulation completely eliminated the C-fibres. Dorsal column stimulation completely eliminated the C-fibre deflection and partially eliminated the A delta-fibre deflection.     

Matrix-mediated gene transfer to brain cortex and dorsal root ganglion neurones by retrograde axonal transport after dorsal column lesion

BACKGROUND: In previous studies, we showed that the immobilisation of DNAs encoding basic fibroblast growth factor, neurotrophin-3 and brain-derived neurotrophic factor in a gene-activated matrix (GAM) promotes sustained survival of axotomised retinal ganglion cells after optic nerve injury. Here, we evaluated if the immobilisation of DNAs in a GAM could be an effective approach to deliver genes to axotomised dorsal root ganglion (DRG) neurones after spinal cord injury and if the matrix component of the GAM would modulate the deposition of a dense scar at the injury site. METHODS: We evaluated the expression of the thymidine kinase (TK) reporter gene in brain cortex and DRG after a bilateral T8 dorsal column (DC) lesion using PCR, RT-PCR and in situ hybridisation analyses. Collagen-based GAMs were implanted at the lesion site and the cellular response to the GAM was assessed using cell-specific markers. RESULTS: At 1 week post-injury, PCR analyses confirmed that DNATK was retrogradely transported from the DC lesion where the GAM was implanted to the brain cortex and to caudal DRG neurones, and RT-PCR analyses showed expression of mRNATK. At 7 weeks post-injury, DNATK was still be detected in the GAM and DRG. In situ hybridisation localised DNATK and mRNATK within fibroblasts, glia, endothelial and inflammatory cells invading the GAM and in DRG neurones. Interestingly, the presence of a GAM also reduced secondary cavitation and scar deposition at the lesion site. CONCLUSIONS: These results establish that GAMs act as bridging scaffolds in DC lesions limiting cavitation and scarring and delivering genes both locally to injury-reactive cells and distally to the cerebral cortex and to DRG neuronal somata through retrograde axonal transport.     

Spinal dorsal column afferent fiber composition in the pigeon: an electrophysiological investigation

Summary The spinal dorsal column of homing pigeons (Colomba livia) was investigated electrophysiologically by recording responses from individual afferent fibers at a high cervical level (segments C4-C5) to mechanical stimulation of wing skin and deep tissue. Of 157 afferent fibers 134 were cutaneous afferents. The remainder were afferents of deep receptors.Thirty of the cutaneous afferents were slowly adapting and 87 rapidly adapting (17 not identified). Rapidly adapting afferents were studied with regard to Pacinianlike characteristics (Herbst corpuscles in birds; vibration sensitive receptors). Of 43 rapidly adapting afferents 38 were classified as afferents of vibration sensitive Herbst corpuscles and 5 as non vibration sensitive rapidly adapting afferents; 44 afferents could not be studied sufficiently with regard to vibrational stimuli. The vibration sensitive Herbst corpuscle afferents had U-shaped vibrational tuning curves and responded best to vibration frequencies of 300 to 400 Hz. The 11 threshold for 300 Hz vibration ranged from 2 to 36 um. Herbst corpuscle afferents always showed strong phase coupling to the stimulus cycle.Afferents of deep receptors showed slowly adapting responses to firm pressure or movements of limbs and were classified as joint receptors. No muscle spindle afferents were encountered.Primary afferent fibers were identified in 89 cases (80 cutaneous and 9 deep), postsynaptic elements in 15 cases (11 cutaneous, 4 deep). Only slowly adapting responses were found in postsynaptic fibers.Abbreviations CV coefficient of variation - EI entrainment index - INTH interval histogram - PSTH peristimulus time histogram - RA rapidly adapting - SA slowly adapting     

Coding of vibration by neurones of the dorsal column nuclei in the pigeon

Whereas the function of mechanoreceptors is well known in birds there are no detailed investigations of central processing. Therefore the characteristics of neurones in a first relay, the dorsal column nuclei (nuclei gracilis et cuneatus and the nucleus cuneatus externus), were studied electrophysiologically by recording responses from individual neurones to mechanical stimulation of skin and deep tissue.Of 140 units 84 were cutaneous neurones. The remainder were tap- and deep-neurones. Tap-neurones were activated by sharp brief taps. Activity in deep-neurones was comparable to joint and tendon receptors but not to muscle spindles. Thirty-four cutaneous neurones were vibration sensitive neurones, 36 were slowly adapting neurones and 14 neurones were rapidly adapting and fast habituating cells. Vibration sensitive neurones were most sensitive to 200 to 500 Hz. Frequencies above 100 Hz elicited phase coupled responses.Within the nn. gracilis et cuneatus 61 were cutaneous neurones, 13 were deep-neurones and 7 were tap-cells. Within n. cuneatus externus 17 were cutaneous units, 21 were deep-neurones and 11 were tap-neurones. No vibration sensitive neurones were found within n. cuneatus externus. This means that coding for vibration is represented in the nn. gracilis et cuneatus.Abbreviations CE n. cuneatus externus - DCN dorsal column nuclei - GC n. gracilis et cuneatus - HC Herbst corpuscle - PH phasic and habituating - Imps./s Impulses per second - INTH interval histogram - PSTH peristimulus time histogram - PHASE Phase histogram - RF receptive field - SA slowly adapting - Vec. vector strength     

Horseradish peroxidase in axons of the dorsal funiculi of the cat: distribution after an injection of the enzyme into the dorsal column nuclei

Horseradish peroxidase (HRP) was injected into the left dorsal column nuclei of adult cats. Large dorsal funiculi axons of the C3, C5, C8 and L7 segments were searched for HRP-activity after 12, 24, 36 and 48rh using light and electron microscopy. Accumulations of intra-axonal HRP-positive bodies occurred at nodes of Ranvier in the C3-C8 segments at 12, 24 and 36rh and in the L7 segments at 24, 36, and 48rh. The accumulations of HRP in three spatio-temporally different consecutive patterns, noted earlier at nodes of Ranvier in the peripheral nervous system (PNS) portion of feline alpha motor axons for more than 70rh after an intramuscular injection of the enzyme, were not observed in the present material. We suggest that the differences in the modes in which large PNS and CNS axons interact with retrogradely transported HRP are due to differences in the organization of the respective nodal regions. We also emphasize that endocytosis via axon terminals in the CNS normally represents uptake of material from an extracellular space which is controlled and protected by the blood-brain barrier. This is in contrast to endocytosis via axon terminals in a muscle, which represents uptake of material from an extracellular space openly exposed to influx of different substances from the blood stream.     

Structural and functional organization of the dorsal column nuclei after unilateral exclusion of the medial lemniscus

The authors studied ultrastructural changes in neurons and alterations in evoked electrical responses after stimulation of the forelegs in the nuclei gracilis and cuneatus one year after unilateral section of the medial lemniscus in cats. It was shown that intact projectional elements of the nuclei gracilis and cuneatus had the normal cytological appearance and functional activity of their synaptical organization in spite of the cytoarchitectonic asymmetry. After disruption of the medial lemniscus the symmetrical nuclei of the dorsal columns did not exhibit any asymmetry in the distribution of evoked responses after stimulation of the forelegs.     

Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury.

Regeneration is abortive following adult mammalian CNS injury. We have investigated whether increasing the intrinsic growth state of primary sensory neurons by a conditioning peripheral nerve lesion increases regrowth of their central axons. After dorsal column lesions, all fibers stop at the injury site. Animals with a peripheral axotomy concomitant with the central lesion show axonal growth into the lesion but not into the spinal cord above the lesion. A preconditioning lesion 1 or 2 weeks prior to the dorsal column injury results in growth into the spinal cord above the lesion. In vitro, the growth capacity of DRG neurite is also increased following preconditioning lesions. The intrinsic growth state of injured neurons is, therefore, a key determinant for central regeneration.     

Excitation of cat spinal cord dorsal column fibers during stimulation of different fiber groups of cutaneous and somatic nerves

The effects of electrically stimulating different groups of nerve fibers supplying the skin and muscle on evoked potentials in cat spinal cord dorsal columns were studied. Significant differences in the configuration of dorsal column potentials recorded in response to stimulation of these nerves were found. It was shown that cutaneous nerve unmyelinated fibres were connected to unmyelinated dorsal column fibers. In addition, excitation of cutaneous C-fibers lead to activation of dorsal column fibers with the maximum conduction velocity. The somatic nerve was only connected to myelinated dorsal column fibers, and excitation of its non-myelinated fibers did not cause other types of dorsal column fibers to be activated. It is suggested that the acceleration of cutaneous signal transmission in the dorsal column system may be brought about by the necessity for rapid warning of potentially harmful stimuli.Medical Institute, Russian Federation Ministry of Public Health, Nizhny Novgorod. Translated from Neirofiziologiya, Vol. 24, No. 5, pp. 625–635, September–October, 1992.     

Discrepancy between SEPs directly recorded from the dorsal column nuclei following upper and lower limb stimulation in patients with syringomyelia

Somatosensory evoked potentials (SEPs) in response to electrical stimulation of the median nerve (MN) and posterior tibial nerve (PTN) were studied in 2 patients with syringomyelia. Intraoperative recordings were made from the surface of the dorsal column nuclei as well as from the scalp. Following MN stimulation, there was a preservation of scalp-recorded P9, P11, P13 and N20, however, there was an absence of spinal N13-P13. The dorsal column SEPs to MN stimulation were normal, characterized by a major negativity (N1), preceded by a small positivity (P1) and followed by a large positivity (P2). On the other hand, there was little or no cortical response (P37) to PTN stimulation. The dorsal column SEPs to PTN stimulation showed a disappearance of the normal P1′-N1′-P2′ configuration, being replaced by a series of small spiky waves. The syringomyelic cavity may have thus compressed the gracile dorsal column which courses more medially than the cuneate pathway, causing desynchronization of the dorsal column SEPs. These findings suggest that dorsal column pathway arising from the lower limb is more vulnerable than that from the upper limb when a cervical syrinx is present.     

The fine structure of the dorsal column nucleus and the nucleus of bischoff of the python (Python reticulatus)

Three types of neuronal perikaryal profiles were identified in the dorsal column nucleus and the nucleus of Bischoff of the python (Python reticulatus). Type I neuronal profiles are large (diameters 12–20 μm) with a deeply indented uncleus. The cisterns of rough endoplasmic reticulum (rER) are mostly randomly dispersed. Axosomatic synapses are few. Type II neuronal profiles (9–11 μm) have a smooth, round, or slightly oval nucleus. Several small stacks of rER are present. Type III neuronal profiles (8–10 μm) have little cytoplasm. The nuclear margin is irregular but not deeply infolded. The rER usually consists of a single long perinuclear ribosome-studded cistern. Two types of astrocytic profiles have been identified. Both types contain abundant filaments. Type I astrocytes are large cells, and the nucleus is very irregular in shape. Type II astrocytes are smaller and are found among the myelinated axons in the dorsal funiculus. Two classes of axon terminals have been identified. One class contains round synaptic vesicles (R profiles) and the other flattened vesicles (F profiles). Some R profiles are small (SR profiles), others are large (LR profiles). Some R profiles also contain a few large, dense-cored vesicles. The R and F profiles establish axodendritic and axoaxonal synapses, some of which are located in the synaptic glomeruli and others in the extraglomerular neuropil. In most of the axoaxonal synapses, the presynaptic element is an F profile and the post synaptic element an LR profile. Occasionally, LR profiles are presynaptic to F profiles. The findings in the python are compared with those of the dorsal column nuclei of the rat, cat, and monkey.     

Long ascending fibers in the dorsal column of a teleost fish: a disynaptic pathway connecting sense organs to cerebellum]

In spite of the generally accepted opinion that long ascending proprioceptive and tactile fibers do not occur in the spinal dorsal columns of teleost fish, it was demonstrated with degeneration and axonal transport tracing methods that such dorsal column fibers exist in the teleost fish Gnathonemus petersii. These fibers are in fact common spinal afferent fibers originating in spinal ganglion cells. They connect the peripheral sense organs with the lateral funicular nuclei (Fl2) in which the dorsal column fibers terminate, directly through the dorsal columns. In contrast to the dorsal column nuclei of higher vertebrates, the Fl2 nuclei do not project to the diencephalic thalamus but to the caudal lobe and the second lobe (C2) of the corpus cerebelli. Thus, sense organs and cerebellum are connected by a disynaptic pathway. Since the caudal lobe projects directly to the electrosensory lobe, that is, to the target of electrosensory afferents, the presence of a disynaptic pathway in G. petersii suggests the existence of a proprioceptive control of the electrosensory input.