Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis: A role for retrograde motors.
Mutations in the genes for components of the dynein-dynactin complex disrupt axon path finding and synaptogenesis during metamorphosis in the Drosophila central nervous system. In order to better understand the functions of this retrograde motor in nervous system assembly, we analyzed the path finding and arborization of sensory axons during metamorphosis in wild-type and mutant backgrounds. In wild-type specimens the sensory axons first reach the CNS 6-12 h after puparium formation and elaborate their terminal arborizations over the next 48 h. In Glued1 and Cytoplasmic dynein light chain mutants, proprioceptive and tactile axons arrive at the CNS on time but exhibit defects in terminal arborizations that increase in severity up to 48 h after puparium formation. The results show that axon growth occurs on schedule in these mutants but the final process of terminal branching, synaptogenesis, and stabilization of these sensory axons requires the dynein-dynactin complex. Since this complex functions as a retrograde motor, we suggest that a retrograde signal needs to be transported to the nucleus for the proper termination of some sensory neurons. (+info)
An unusual case of thoracic outlet syndrome associated with long distance running.
An amateur marathon runner presented with symptoms of thoracic outlet syndrome after long distance running. He complained of numbness on the C8 and T1 dermatome bilaterally. There were also symptoms of heaviness and discomfort of both upper limbs and shoulder girdles. These symptoms could be relieved temporarily by supporting both upper limbs on a rail or shrugging his shoulders. The symptoms and signs would subside spontaneously on resting. An exercise provocative test and instant relief manoeuvre, which are the main diagnostic tests for this unusual case of "dynamic" thoracic outlet syndrome, were introduced. (+info)
Sacral neural crest cell migration to the gut is dependent upon the migratory environment and not cell-autonomous migratory properties.
Avian neural crest cells from the vagal (somite level 1-7) and the sacral (somite level 28 and posterior) axial levels migrate into the gut and differentiate into the neurons and glial cells of the enteric nervous system. Neural crest cells that emigrate from the cervical and thoracic levels stop short of the dorsal mesentery and do not enter the gut. In this study we tested the hypothesis that neural crest cells derived from the sacral level have cell-autonomous migratory properties that allow them to reach and invade the gut mesenchyme. We heterotopically grafted neural crest cells from the sacral axial level to the thoracic level and vice versa and observed that the neural crest cells behaved according to their new position, rather than their site of origin. Our results show that the environment at the sacral level is sufficient to allow neural crest cells from other axial levels to enter the mesentery and gut mesenchyme. Our study further suggests that at least two environmental conditions at the sacral level enhance ventral migration. First, sacral neural crest cells take a ventral rather than a medial-to-lateral path through the somites and consequently arrive near the gut mesenchyme many hours earlier than their counterparts at the thoracic level. Our experimental evidence reveals only a narrow window of opportunity to invade the mesenchyme of the mesentery and the gut, so that earlier arrival assures the sacral neural crest of gaining access to the gut. Second, the gut endoderm is more dorsally situated at the sacral level than at the thoracic level. Thus, sacral neural crest cells take a more direct path to the gut than the thoracic neural crest, and also their target is closer to the site from which they initiate migration. In addition, there appears to be a barrier to migration at the thoracic level that prevents neural crest cells at that axial level from migrating ventral to the dorsal aorta and into the mesentery, which is the portal to the gut. (+info)
Heterogenous patterns of sensory dysfunction in postherpetic neuralgia suggest multiple pathophysiologic mechanisms.
BACKGROUND: Postherpetic neuralgia (PHN) is considered by some investigators to be predominantly a deafferentation-type central pain syndrome; others suggest that activity of remaining peripheral nociceptors plays a critical role. The authors investigated the sensory dysfunction in subjects with PHN of varying duration and at different sites to gain further insight into the mechanisms responsible for the clinical features of neuropathic pain. In addition, the relationships between ongoing pain and pain evoked by mechanical and thermal stimuli were compared in patients with trigeminal and truncal PHN, to determine if the pathophysiologic mechanisms differed among subjects. METHODS: In 63 subjects with PHN, quantitative sensory testing was performed in the region of maximum allodynia or ongoing pain and the corresponding contralateral site. The intensity of ongoing pain was recorded. Sensory thresholds for warmth, coolness, heat pain, and cold pain were determined. Pain induced by various mechanical stimuli (dynamic, static, punctate) was rated using a numerical rating scale of 0-10. RESULTS: The mean rating of ongoing PHN pain was 7.3 +/- 2.0 (mean +/- SD). Allodynia induced by one or more mechanical stimuli was observed in 78% of subjects. A smaller subset (40%) had hyperalgesia to heat or cold stimuli. In subjects with duration of PHN of < or = 1 yr duration, but not in those with duration of > 1 yr, the intensity of ongoing pain correlated with intensity of allodynia induced by dynamic stimuli. Deficits in thresholds for heat and cold pain were observed in the affected region of subjects with PHN in the thoracic dermatomes (P < 0.005), but not in the trigeminal distribution. No relationship was observed between the thermal deficits and ongoing pain or mechanical allodynia in the groups of subjects with either trigeminal or thoracic PHN. CONCLUSION: Despite a common cause, the patterns of sensory abnormalities differ between subjects. Particular differences were noted between groups with facial or truncal PHN and between groups with recent or more chronic PHN. The observations suggest that the relative contributions of peripheral and central mechanisms to the pathophysiology of pain differ among subjects and may vary over the course of PHN. (+info)
The effects of prolonged repetitive stimulation in hemicholinium on the frog neuromuscular junction.
1. Cutaneous pectoris nerve-muscle preparations from the frog were stimulated for prolonged periods in solutions with curare alone, curare and hemicholinium no. 3 (HC-3), or curare and glucose plus choline. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) were recorded intracellularly. Black widow spider venom (BWSV) was applied to determine the degree of depletion of the transmitter stores. 2. The ultrastructure of the neuromuscular junctions was studied in the electron microscope. Some of the preparations were fixed immediately at the end of the period of stimulation and others were fixed about an hour after BWSV had been applied. In some experiments horseradish peroxidase (HRP) was present during the period of stimulation and the fixed tissue was treated to reveal the distribution of the tracer. 3. The amplitude of the e.p.p. fell rapidly to almost zero during 2 hr of stimulation at 2/sec in 100 muM HC-3 and little recovery occurred during a subsequent hour of rest. About 2-7 times 10-5 quanta were secreted. The e.p.p.s usually persisted throughout the period of stimulation in the other solutions and 2-2-6 times as much transmitter was secreted. 4. When BWSV was applied immediately at the end of the period of stimulation in HC-3, almost no m.e.p.p.s were discharged and only small m.e.p.p.s were discharged when the venom was applied after an hour of rest. 5. When BWSV was applied to unstimulated terminals that had been bathed in HC-3, or to terminals that had been stimulated and rested for an hour in glucose plus choline, m.e.p.p.s of nearly normal amplitude were discharged. 6. Terminals stimulated for 2 hr at 2/sec in 100 muM HC-3 contained a normal complement of synaptic vesicles and a large proportion of vesicles were labelled with HRP when the tracer was present during the period of stimulation. 7. BWSV induced the almost complete depletion of vesicles from terminals that had been stimulated in HC-3. 8. Depletion of vesicles also occurred when terminals were stimulated for 20 min at 10/sec after they had been previously stimulated for 2 hr at 2/sec in HC-3. These terminals showed extensive infolding of the axolemma and they contained swollen mitochondria. 9. These results indicate that stimulation in HC-3 depletes terminals of their store of transmitter but not of their population of vesicles and that vesicles empty of transmitter can fuse with and reform from the axolemma of the nerve terminal. (+info)
Retroambiguus projections to the cutaneus trunci motoneurons may form a pathway in the central control of mating.
Our laboratory has proposed that the nucleus retroambiguus (NRA) generates the specific motor performance displayed by female cats during mating and that it uses direct pathways to the motoneurons of the lower limb muscles involved in this activity. In the hamster a similar NRA-projection system could generate the typical female mating posture, which is characterized by lordosis of the back as well as elevation of the tail. The present study attempted to determine whether this elevation of the tail is also part of the NRA-mating control system. The basic assumption was that elevation of the tail is a function of the cutaneous trunci muscle (CTM), which was verified by bilateral tetanic stimulation of the lateral thoracic nerves innervating the CTM. It resulted in upward movement of the tail to a position similar to the tail-up position during the lordosis posture. Retrograde tracing results showed that CTM motoneurons are located in the ventral and ventrolateral part of the C(7)-C(8) ventral horn, those innervating the tail region ventrolateral to those innervating the axillary region. Anterograde tracing studies showed that NRA fibers terminate bilaterally in both parts of the CTM motoneuronal cell groups. Electron microscopical studies revealed that labeled NRA terminals make monosynaptic contacts with retrogradely labeled dendrites of CTM motoneurons. Almost all of these terminal profiles had asymmetric synapses and contained spherical vesicles, which suggests an excitatory function. The observation that 15% of the labeled NRA terminals make more than one synaptic contact with a retrogradely labeled CTM motoneuronal dendrite within the same section indicates how powerful the NRA-CTM projection is. The results indicate that during mating the NRA not only could generate the lordosis posture but also the elevation of the tail. (+info)
Mechanism of glia-neuron cell-fate switch in the Drosophila thoracic neuroblast 6-4 lineage.
During development of the Drosophila central nervous system, neuroblast 6-4 in the thoracic segment (NB6-4T) divides asymmetrically into a medially located glial precursor cell and a laterally located neuronal precursor cell. In this study, to understand the molecular basis for this glia-neuron cell-fate decision, we examined the effects of some known mutations on the NB6-4T lineage. First, we found that prospero (pros) mutations led to a loss of expression of Glial cells missing, which is essential to trigger glial differentiation, in the NB6-4T lineage. In wild-type embryos, Pros protein was localized at the medial cell cortex of dividing NB6-4T and segregated to the nucleus of the glial precursor cell. miranda and inscuteable mutations altered the behavior of Pros, resulting in failure to correctly switch the glial and neuronal fates. Our results suggested that NB6-4T used the same molecular machinery in the asymmetric cell division as other neuroblasts in cell divisions producing ganglion mother cells. Furthermore, we showed that outside the NB6-4T lineage most glial cells appeared independently of Pros. (+info)
Scapulothoracic stabilisation for winging of the scapula using strips of autogenous fascia lata.
We have used a modified technique in five patients to correct winging of the scapula caused by injury to the brachial plexus or the long thoracic nerve during transaxillary resection of the first rib. The procedure stabilises the scapulothoracic articulation by using strips of autogenous fascia lata wrapped around the 4th, 6th and 7th ribs at least two, and preferably three, times. The mean age of the patients at the time of operation was 38 years (26 to 47) and the mean follow-up six years and four months (three years and three months to 11 years). Satisfactory stability was achieved in all patients with considerable improvement in shoulder function. There were no complications. (+info)