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At least 361 records · Page 20Linked to original sources

Ribosomal RNA in Mauthner axon: implications for a protein synthesizing machinery in the myelinated axon.

RNA was extracted from myelin-free Mauthner axons of the goldfish on a microscale and fractionated by microelectrophoresis. Microextracts showed the presence of nominal 26 SE, 18 SE, 5 SE and 4 SE components, which co-migrated with rRNA from fish brain. In addition, a non-ribosomal 15 SE component was present in axon microextracts, but not in RNA extracts of fish brain or of myelin sheath from Mauthner axon, indicating an unusual enrichment of a putative mRNA class. Evidence was presented to support the contention that axonal rRNA was not due to contamination from the myelin sheath. Possible reasons for the lack of ultrastructural evidence for axoplasmic ribosomes are discussed.

Animals↗

Short-axon neurons with two axon-like processes in the visual cortex of the cat. A Golgi study.

In the visual cortex (areas 17, 18 and 19) of adult cats and a 40-day-old kitten, short-axon cells with two axon-like processes are described. These neurons belong to different cell types (spineless stellates of layers II/III and IV, fusiform cells of layers III, IV and V, and a large multipolar spineless cell of layer III). The axon-like processes present the same morphological characteristics as single axons of the corresponding neuronal type.

Animals↗

The relation between axon diameter and axonal conduction velocity of Y, X and W cells in the cat retina.

Axon diameters of ganglion cells were measured electronmicroscopically from the cross-sections of the optic nerve fiber layer in the cat retina. The diameter distribution revealed 3 well-separated groups which correspond to axons of Y, X and W cells. Mean intraretinal axonal conduction velocities were estimated physiologically for the 3 classes. Between the means of axon diameter (D, micron) and conduction velocity (V, m/s) the following positive correlations were obtained: V = 3.85 square root D-2.3 when short axes of cross-sections were measured, and V = 3.33 square root D-2.3 when long axes were measured.

Animals↗

Anterograde to retrograde reversal of fast axonal transport within cold blocked and rewarmed intact axons.

The possibility that anterograde to retrograde reversal of axonal transport might take place in mid axon at a site distant from any nerve termination was investigated in sciatic nerve preparations from Xenopus laevis. The nerve, containing a pulse of anterogradely transported protein labeled with [35S]methionine, was kept in a two-compartment temperature controlled chamber. One compartment containing the proximal nerve was maintained at room temperature throughout the duration of an experiment while the second compartment containing the distal nerve, and separated from the first by a thermal barrier, was initially cooled to 3-4 degrees C and later warmed to room temperature. Transport of labeled proteins in the nerve was detected with a position-sensitive detector of ionizing radiation. With the distal portion of the nerve cold, the pulse of labeled protein transported up to the thermal barrier and stopped. When the distal part of the nerve was warmed to room temperature, retrograde and anterograde pulses of label propagated away from the thermal barrier with no time delay. The retrograde pulse could be collected on the distal side of a proximally placed tie and could be eliminated by treatment of the proximal nerve with vinblastine or dinitrophenol. Functional and structural evidence indicated that the cold block and thermal barrier were not destructive to the axons. Electron microscopy showed that the numerical density of axonal microtubules distal to the cold block was decreased about seven fold during the cold treatment and that this decrease could be prevented by 10 mumol/l taxol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Proteins of fast axonal transport in regenerating rat sciatic sensory axons: a conditioning lesion does not amplify the characteristic response to axotomy.

The regeneration rate of axons following injury can be influenced by the past history of the neuron: if an axon received a "conditioning" lesion its regeneration rate from a subsequent "test" lesion is increased. Because regeneration is associated with the increased synthesis and fast axonal transport of growth-associated proteins of unknown functions, we investigated whether the increased regeneration rate (to 81%) seen in conditioned rat sciatic sensory axons following a test lesion was associated with an amplification of the increase in growth-associated protein expression. The test lesion did not produce any amplification of the increase in growth-associated protein expression resulting from the preceding conditioning lesion. We conclude that this aspect of the cell body reaction to axotomy is not involved in the conditioning lesion effect on regeneration rate, and, as a corollary, it appears that fast-transported proteins whose expression alters after axotomy are not involved in the regulation of the regeneration rate.

Animals↗

Measurement of axonal conduction velocity in single mammalian motor axons.

In deeply anesthetized cats, determinations of motor-axonal conduction velocity (CV) were made using extracellular potentials recorded from single, functionally isolated motor axons innervating the muscle tibialis posterior. Axons were activated by suprathreshold electrical stimulation at the ventral-root level. Action potentials were recorded with 3 bipolar electrodes located on the muscle nerve at the level of the popliteal fossa. The most proximal and distal of the bipolar muscle-nerve electrodes were 16.4-22.0 mm apart. Estimates were made of CV from ventral root to muscle nerve (conventional CV) and between the proximal and the distal pairs of muscle-nerve electrodes (muscle-nerve CV). An evaluation was based on comparison of these CVs, estimates of uncertainties in time and distance measurements and simulations of the effects of recording conditions on CV estimates. The analysis indicated that the uncertainty in the conventional CV measurement of mammalian motor axons is at least +/- 2%. However, variability may be as great as 20% between muscle-nerve CV measurements from different experiments, probably due to such factors as regional variation in CV and differences in recording configuration.

Action Potentials↗

Anterograde axonal tracing with the subunit B of cholera toxin: a highly sensitive immunohistochemical protocol for revealing fine axonal morphology in adult and neonatal brains.

We report an improved immunohistochemical protocol for revealing anterograde axonal transport of the subunit B of cholera toxin (CTB) which stains axons and terminals in great detail, so that single axons can be followed over long distances and their arbors reconstructed in their entirety. Our modifications enhance the quality of staining mainly by increasing the penetration of the primary antibody in the tissue. The protocol can be modified to allow combination in alternate sections with tetramethylbenzidine (TMB) histochemical staining of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Using the protocol, we tested the performance of CTB as an anterograde tracer under two experimental paradigms which render other anterograde tracers less sensitive or unreliable: (1) labeling the entire retinofugal projection to the brain after injections into the vitreal chamber of the eye, and (2) labeling developing projections in the cortex and thalamus of early postnatal mammals. Qualitative comparisons were made with other tracers (Phaseolus vulgaris leucoagglutinin, dextran rhodamine, biotinylated dextran, free WGA, or WGA-HRP) that were used to label these same projections. From these observations it is clear that CTB, visualized with our protocol, provides more sensitive anterograde labeling of retinofugal projections as well as of axonal connections in the neonatal forebrain.

Animals↗

Floor plate chemoattracts crossed axons and chemorepels uncrossed axons in the vertebrate brain.

In the bilaterally symmetrical vertebrate CNS, all developing axons must choose between remaining on the same side of the midline or growing across it. The mechanism underlying this axonal pathfinding is, however, poorly understood. Here we demonstrate that the ventral midline floor plate (FP) chemorepels two types of ipsilaterally projecting axons, one from the alar plate and another from the basal plate in the mesencephalon. We further demonstrate that the FP chemoattracts contralaterally projecting myelencephalic as well as metencephalic axons. The FP at all axial levels displayed both chemoattractive and chemorepellent activities, suggesting that FP chemoattraction and chemorepulsion may be at work throughout the neuraxis. Chemotropic guidance by the FP may therefore play a key role in the establishment of neuronal projection laterality.

Animals↗

Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation.

Neuronal migration and axon guidance constitute fundamental processes in brain development that are generally studied independently. Although both share common mechanisms of cell biology and biochemistry, little is known about their coordinated integration in the formation of neural circuits. Here we show that the development of the thalamocortical projection, one of the most prominent tracts in the mammalian brain, depends on the early tangential migration of a population of neurons derived from the ventral telencephalon. This tangential migration contributes to the establishment of a permissive corridor that is essential for thalamocortical axon pathfinding. Our results also demonstrate that in this process two different products of the Neuregulin-1 gene, CRD-NRG1 and Ig-NRG1, mediate the guidance of thalamocortical axons. These results show that neuronal tangential migration constitutes a novel mechanism to control the timely arrangement of guidance cues required for axonal tract formation in the mammalian brain.

Animals↗

Neural repetitive firing: modifications of the Hodgkin-Huxley axon suggested by experimental results from crustacean axons.

The Hodgkin-Huxley equations for space-clamped squid axon (18 degrees C) have been modified to approximate voltage clamp data from repetitive-firing crustacean walking leg axons and activity in response to constant current stimulation has been computed. The m infinity and h infinity parameters of the sodium conductance system were shifted along the voltage axis in opposite directions so that their relative overlap was increased approximately 7 mV. Time constants tau m and tau h, were moved in a similar manner. Voltage-dependent parameters of delayed potassium conductance, n infinity and tau n, were shifted 4.3 mV in the positive direction and tau n was uniformly increased by a factor of 2. Leakage conductance and capacitance were unchanged. Repetitive activity of this modified circuit was qualitatively similar to that of the standard model. A fifth branch was added to the circuit representing a transient potassium conductance system present in the repetitive walking leg axons and in other repetitive neurons. This model, with various parameter choices, fired repetitively down to approximately 2 spikes/s and up to 350/s. The frequency vs. stimulus current plot could be fit well by a straight line over a decade of the low frequency range and the general appearance of the spike trains was similar to that of other repetitive neurons. Stimulus intensities were of the same order as those which produce repetitive activity in the standard Hodgkin-Huxley axon. The repetitive firing rate and first spike latency (utilization time) were found to be most strongly influenced by the inactivation time constant of the transient potassium conductance (tau b), the delayed potassium conductance (tau n), and the value of leakage conductance (gL). The model presents a mechanism by which stable low frequency discharge can be generated by millisecond-order membrane conductance changes.

Action Potentials↗

Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo.

Topographic maps, which maintain the spatial order of neurons in the order of their axonal connections, are found throughout the nervous system. In the visual retinotectal projection, ELF-1, a ligand in the tectum, and its receptors in the retina show complementary gradients in expression and binding, indicating they may be positional labels for map development. Here we show that ELF-1 acts as a repellent axon guidance factor in vitro. In vivo, when the tectal ELF-1 pattern is modified by retroviral overexpression, retinal axons avoid ectopic ELF-1 patches and map to abnormally anterior positions. All these effects were seen on axons from temporal but not nasal retina, indicating that ELF-1 could determine nasal versus temporal retinotectal specificity, and providing a direct demonstration of a cell recognition molecule with topographically specific effects on neural map development.

Animals↗

Two substrates for medial forebrain bundle self-stimulation: myelinated axons and dopamine axons.

The directly activated substrates for medial forebrain bundle (MFB) self-stimulation are primarily low threshold, myelinated axons with absolute refractory periods of 0.4 to 1.2 msec, conduction velocities of 1 to 8 m/sec and current-distance constants of 1000 to 3000 microA/mm2. When small electrode tips or high currents are used, however, a second population of long refractory period (1.2 to 5 msec) axons is added. The excitability properties of this second population are almost identical with those of dopamine (DA) axons. Furthermore, the long-refractory period effects of MFB self-stimulation are reduced, but not completely blocked, by peripheral injections of alpha-flupenthixol, suggesting that dopamine axons make small contributions to MFB self-stimulation when small tips are used. Collision data, strength-duration data and refractory period data in various self-stimulation experiments are compared. Asymmetric collision effects, recently observed in cortical and striatal sites mediating electrically evoked turning, may help determine where synapses are located in circuits mediating electrically evoked behaviors. A neural model of symmetric, asymmetric and mixed collision is proposed.

Animals↗

Sorting signals and targeting of infectious agents through axons: an annotation to the 100 years' birth of the name "axon".

A brief review is given on mechanisms by which axons may be initiated during development and by which the polarity of neurons is maintained by selective sorting and delivery of molecules to axons and dendrites. The use of viruses as tools to study targeting of newly synthesized proteins to axons is described. Emphasis is then given to the hazards that are presented to the individual by the retrograde transport of infectious agents in axons to the brain. Borna disease virus, prions, and Listeria monocytogenes are examined briefly as examples of these mechanisms. These agents have attracted interest previously in veterinary medicine for the most part, but they may present potential and substantial threats to human health. Such infectious agents also represent a new type of virus, a new principle for disease transmission, and a new mechanism for intracellular transport, respectively.

Animals↗

Genetic analysis of Netrin genes in Drosophila: Netrins guide CNS commissural axons and peripheral motor axons.

Two tandem Netrin genes in Drosophila are expressed at the midline of the developing CNS and in different subsets of neurons, muscles, and epidermal patches. In embryos carrying a small deficiency that deletes both genes, CNS axon commissures are partially missing or thinner. This phenotype is rescued by expressing either Netrin gene at the midline. Pan-neural expression of either gene causes disruption of commissural and longitudinal tracts, indicating that the pattern of Netrin expression is crucial and that Netrins function as instructive cues. The double mutant also shows defects in motor axon projections. Expression of either Netrin gene in all muscles also results in aberrant motor projections. Thus, Drosophila Netrins are required for the guidance of commissural axons at the midline, and of motor axons to their target muscles.

Animals↗

Axon-glia interactions modulate axonal excitability in mammalian unmyelinated nerves.

A period of electrical activity in unmyelinated nerve fibers is followed by a post-tetanic hyperpolarization (PTH), generated by the hyperactivity of the electrogenic Na(+)-K(+) pump. In order to protect the membrane potential against these strong hyperpolarizations, different types of axonal inward currents are activated during the PTH. We investigated in the rabbit vagus nerve one of these currents, which was activated by carbamylcholine (CCh). We observed that the effect of CCh on the PTH amplitude could be blocked or reversed with scopolamine. Moreover, the PTH amplitude increased when scopolamine alone was added to the perfusate, indicating that an endogenous muscarinic agonist was liberated in the preparation during the period of electrical activity. This CCh-activated current was TEA but not Ba(2+) or Cs(+) sensitive. It has been shown previously that muscarinic acetylcholine receptors (mAChRs) in the rabbit vagus nerve are located on the axonal but not glial membrane and that Schwann cells express several types of purinergic receptors, which activation evoke Ca(2+) transients in Schwann cells. We hypothesise that during electrical activity axons release a transmitter, presumably ATP. This transmitter evoke in the neighbouring Schwann cells a Ca(2+)-dependent liberation of a endogenous muscarinic agonist, which in turn activates a TEA-sensitive inward current in axons. We suggest that the major purpose of this mechanism is the control of the membrane potential during and after a period of intense electrical activity when the Na(+)-K(+) pump generates a robust PTH.

Animals↗

Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres.

Clinical trials are under way using fetal cells to repair damaged neuronal circuitry. However, little is known about how transplanted immature neurons can grow anatomically correct connections in the adult central nervous system (CNS). We transplanted embryonic porcine neural cells in vivo into adult rat brains with neuronal and axonal loss typical of Parkinson's or Huntington's disease. Using complementary species-specific cellular markers, we found donor axons and CD44+ astroglial fibres in host white matter tracts up to 8 mm from CNS transplant sites, although only donor axons were capable of reaching correct gray matter target regions. This work demonstrates that adult host brain can orient growth of transplanted neurons and that there are differences in transplant donor glial and axonal growth patterns in cellular repair of the mature CNS.

Animals↗

Neuronal dynamics and axonal flow. V. The semisolid state of the moving axonal column.

Evidence assembled since the first comprehensive description of "axonal flow", by deformation analysis, electron microscopy, cinemicrography, and microrheology, has confirmed that the axon of the mature neuron is (a) a semisolid column; (b) in cellulifugal motion at about 1 mum/min (1 mm per day); (c) continuously reproduced at its perikaryal base; (d) propelled by a microperistaltic pulse wave in its surface; and (e) undergoing internal dissolution at the nerve ending. The axon thus "flows" as a structural entity ("axonal flow"), in contradistinction to fast "intraaxonal transport" of molecules and molecular assemblies along internal routes and by mechanisms that are still unknown.

Axonal Transport↗

Neurofascin induces neurites by heterophilic interactions with axonal NrCAM while NrCAM requires F11 on the axonal surface to extend neurites.

Neurofascin and NrCAM are two axon-associated transmembrane glycoproteins belonging to the L1 subgroup of the Ig superfamily. In this study, we have analyzed the interaction of both proteins using neurite outgrowth and binding assays. A neurofascin-Fc chimera was found to stimulate the outgrowth of tectal cells when immobilized on an inert surface but not as a soluble form using polylysine as substrate. Antibody blocking experiments demonstrate that neurite extension on immobilized neurofascin is mediated by NrCAM on the axonal surface. Under the reverse experimental conditions where NrCAM induces neurite extension, F11, and not neurofascin, serves as axonal receptor. Binding studies using transfected COS7 cells and immunoprecipitations reveal a direct interaction between neurofascin and NrCAM. This binding activity was mapped to the Ig domains within neurofascin. The neurofascin-NrCAM binding can be modulated by alternative splicing of specific stretches within neurofascin. These studies indicate that heterophilic interactions between Ig-like proteins implicated in axonal extension underlie a regulation by the neuron.

Animals↗