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PubMed1988

Trigeminal alveolar nerve of the lower jaw in the cichlid Tilapia mariae: evidence for continual axon generation and presence of exceptionally small myelinated axons.

Cross sections from the trigeminal alveolar nerve of the lower jaw in the cichlid Tilapia mariae were examined by electron microscopy. The nerve fibers are arranged in groups with a core of unmyelinated and small myelinated axons, surrounded by myelinated axons of varying sizes. The core contains large bundles of unmyelinated axons collectively ensheathed by circumferentially located Schwann cells, as well as smaller bundles of unmyelinated axons partly separated from each other by Schwann cell processes. Among the unmyelinated axons, occasional scattered profiles resembling growth cones are seen. The total number of axons in this tooth-related nerve increases from approximately 1,500 to 5,000, as the animals grow in length from 4.5 to 21.5 cm. Some 24-49% of the axons are unmyelinated. The myelinated axons have maximum diameters of 1.0-3.0 micron, depending on body size. Most myelinated axons have diameters less than 1.0 micron and the smallest ones reach down to 0.3 micron. These results show that there is a continual addition of axons to the alveolar nerve of the lower jaw in Tilapia mariae and that the critical diameter for myelination in this peripheral nerve is similar to that typically found in the mammalian CNS.

Animals↗
PubMed2000

Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H.

Neurofilament proteins (NFs) are made by co-polymerization of three intermediate filament proteins, NF-L, NF-M and NF-H and constitute the most abundant cytoskeletal element in large myelinated axons. NFs have a well-established role as intrinsic determinants of axon caliber with all the functional implications, but the role of each individual NF subunit is much less clear. The aim of our study was to examine functional properties of large myelinated axons with altered morphology from mice bearing a targeted disruption of each NF genes (NF-L -/-, NF-M-/- and NF-H -/- mice). Membrane properties, action potentials and single axon refractory period were measured in isolated sciatic nerves in vitro, using intra-axonal microelectrode recording in conjunction with current-clamp technique. Some results were obtained from whole nerves by sucrose-gap recording. The NF-knockout mice showed several deficits in physiological properties of low-threshold fibers. In keeping with smaller axon diameter, the conduction velocity was significantly decreased in NF-L -/- and NF-M -/- transgenic animals (control, 39.9+/-1.8 m/s, NF-M -/-; 23.5+/-1. 4 m/s, and NF-L-/-; 12.0+/-0.7 m/s, mean+/-S.E.M.; intra-axonal recording; similar ratios obtained by sucrose-gap recording; 22-26 degrees C). However, in spite of their preserved caliber, large myelinated axons in NF-H -/- mice also showed a significant decrease in conduction velocity (22.8+/-1.0 m/s, mean+/-S.E.M.). Although action potential amplitudes, duration and shape did not differ between control axons and transgenic animals, the refractory period was prolonged in NF-H -/- and NF-M -/- animals. Intracellular injections of 200 ms depolarizing and hyperpolarizing currents revealed outward and inward rectification in all animal groups. In comparison to control animals, NF-H -/- mice expressed a significant decrease in outward rectification. Potassium channel blockers (4AP and TEA) and cesium ions were able to block outward and inward rectification in all myelinated axons in qualitatively the same manner. These results suggest that NF-H may have a specific role in modulating ion channel functions in large myelinated fibers.

Action Potentials↗
PubMed2002

Model of spike propagation reliability along the myelinated axon corrupted by axonal intrinsic noise sources.

We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulating the axons with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same.

Action Potentials↗
PubMed1978

A morphological study of the axons and recurrent axon collaterals of cat sciatic alpha-motoneurons after intracellular staining with horseradish peroxidase.

Utilizing the centrifugal neuronal transport of intracellularly injected horseradish peroxidase (HRP), we have performed a light microscopic (LM) investigation of the intramedullary parts of the axons and axon collaterals of sciatic alpha-motoneurons in the adult cat. The intramedullary parts of the alpha-motor axons had comparatively short internodes (down to 75 microns) and were thinner than reported in earlier studies on the ventral root. Positive correlations were obtained when relating nodal diameters (2.8-7.8 micron) or the mean diameters of the motor axons in the white matter (4.4-9.0 micron) to the diameters of the initial axonal segments (2.3-4.9 micron). Eighty percent of the motor axons gave off one to five collaterals. There was no correlation between the numbers of collaterals and the lengths of the parent motor axons in the gray matter. The branching patterns of the axon collaterals showed considerable variation and the number of end branches from a single collateral ranged between 1 and 39. The rostro-caudal distribution of the collateral end branches was arranged symmetrically within a narrow space (+/- 300 micron) around the origins of the first order collaterals. Outbulgings of the motor axon collaterals, interpreted as synaptic terminals, were found along (59%) or at the ends (41%) of the collateral branches, and were located 200-700 micron away from the origin of the first order collateral. No characteristic LM feature of the outbulgings was distinguished.

Animals↗
PubMed1992

Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells.

Studies in Trembler and control mice demonstrated that myelinating Schwann cells exert a profound influence on axons. Extensive contacts between myelin and axons have been considered structural. However, demyelination decreases neurofilament phosphorylation, slow axonal transport, and axonal diameter, as well as significantly increasing neurofilament density. In control sciatic nerves with grafted Trembler nerve segments, these changes were spatially restricted: they were confined to axon segments without normal myelination. Adjacent regions of the same axons had normal diameters, neurofilament phosphorylation, cytoskeletal organization, and axonal transport rates. Close intercellular contacts between myelinating Schwann cells and axons modulate a kinase-phosphatase system acting on neurofilaments and possibly other substrates. Myelination by Schwann cells sculpts the axon-altering functional architecture, electrical properties, and neuronal morphologies.

Animals↗
PubMed2005

Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury.

Traumatic axonal injury (TAI) following traumatic brain injury (TBI) remains a clinical problem for which no effective treatment exists. TAI was thought to involve intraaxonal changes that universally led to impaired axonal transport (IAT), disconnection and axonal bulb formation. However, recent, immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and antibodies to neurofilament compaction (NFC), RM014, demonstrated that NFC typically occurs independent of IAT, indicating the existence of different populations of damaged axons. FK506 administration has been shown to attenuate IAT. However, in light of the above, the ability of FK506 to attenuate axonal damage demonstrating NFC requires evaluation. The current study explored the potential of FK506 to attenuate both populations of damaged axons. Rats were administered FK506 (3 mg/kg) or vehicle 30 min preinjury. Three hours post-TBI, tissue was prepared for the visualization of TAI using antibodies targeting IAT (APP) or NFC (RMO14) or a combined labeling strategy. Confirming previous reports, FK506 treatment reduced the number of axons demonstrating IAT in the CSpT, from 411 +/- 54.70 to 91.00 +/- 33.87 (P <or= 0.05) and in the ML from 78.62 +/- 16.87 to 41.00 +/- 5.80 (P <or= 0.05). FK506 treatment failed to reduce the number of axons demonstrating NFC in either the CSpT or ML. FK506's failure to attenuate NFC suggests that additional therapeutic agents may be necessary to blunt the full burden of TAI. Because FK506 targets IAT, calcineurin appears to be a major target for neuroprotection in damaged axons demonstrating IAT.

Amyloid beta-Protein Precursor↗
PubMed1979

Slowly migrating axonal polypeptides. Inequalities in their rate and amount of transport between two branches of bifurcating axons.

Polypeptides in the dorsal root ganglion (L5) of the adult rat were radioactively labeled, and components slowly migrating in the sciatic nerve (peripheral axons) and dorsal root (central axons) were analyzed, using SDS-polyacrylamide slab gel electrophoresis and fluorography. In particular, the transport rates and amounts of six major polypeptides, i.e., the triplet (reference 15; with mol wts of 200,000, 160,000, and 68,000 daltons), alpha- and beta-tubulins and actin were compared between the two axon branches. In peripheral axons, fronts of the triplet, tubulins, and actin migrate at 2-3 mm/d, 9-13 mm/d and approximately 19 mm/d, respectively. The corresponding values in central axons are 1-2 mm/d, 3-4 mm/d, and approximately 4 mm/d, indicating an obvious asymmetry in the transport rate between the two branches of bifurcating axons. A greater amount of labeled triplet, tubulins, and actin each is found to migrate in peripheral than in central axons. Another striking aspect of asymmetry between the two branches relates to the tubulins/triplet ratio which is significantly higher in the peripheral branch. Considerable proportions of radioactivities associated with tubulins and actin in the ganglion are nonmigratory, which are thought to derive mostly from periaxonal satellite cells. In contrast, most if not all of the labeled triplet is migratory, suggesting a virtual absence of triplet polypeptides in satellite cells. The possible significance of peripheral-central inequalities in slow axoplasmic transport is discussed from the viewpoints of axon volume and axonal outgrowth.

Actins↗
PubMed1997

Axonal structure and function after axolemmal leakage in the squid giant axon.

Membrane leakage is a common consequence of traumatic nerve injury. In order to measure the early secondary effects of different levels of membrane leakage on axonal structure and function we studied the squid giant axon after electroporation at field strengths of 0.5, 1.0, 1.6, or 3.3 kV/cm. Immediately after mild electroporation at 0.5 kV/cm, 40% of the axons had no action potentials, but by 1 h all of the mildly electroporated axons had recovered their action potentials. Many large organelles (mitochondria) were swollen, however, and their transport was reduced by 62% 1 h after this mild electroporation. One hour after moderate electroporation at 1.0 kV/cm, most of the axons had no action potentials, most large organelles were swollen, and their transport was reduced by 98%, whereas small organelle transport was reduced by 75%. Finally at severe electroporation levels of 1.65-3.0 kV/cm all conduction and transport was lost and the gel-like axoplasmic structure was clumped or liquefied. The structural damage and transport block seen after severe and moderate poration were early secondary injuries that could be prevented by placing the porated axons in an intracellular-type medium (low in Ca2+, Na+, and Cl-) immediately after poration. In moderately, but not severely, porated axons this protection of organelle transport and structure persisted, and action potential conduction returned when the axons were returned to the previously injurious extracellular-type medium. This suggests that the primary damage, the axolemmal leak, was repaired while the moderately porated axons were in the protective intracellular-type medium.

Animals↗
PubMed1989

Axonal degeneration and axonal caliber alterations following combined beta,beta'-iminodipropionitrile (IDPN) and acrylamide administration.

A new model of neurofilamentous axonal abnormality is described which employs combined administration of beta,beta'-iminodipropionitrile (IDPN) and acrylamide (AC). The model was developed to test the hypothesis that IDPN-induced swelling increases the vulnerability of the distal axon to a second neurotoxic chemical insult. Rats were given a single intraperitoneal (IP) injection of IDPN (1.5 g/kg) one week before receiving a single injection of AC (75 mg/kg, IP). Axonal degeneration was observed at multiple levels along the sciatic nerve at two weeks (with reference to IDPN administration), and was not progressive up to five weeks. Quantitation of degenerating fibers demonstrated that the extent of degeneration increased distally along the sciatic nerve. Single administration of either IDPN or AC did not produce degeneration. Thus, IDPN-induced neurofilamentous swellings alter the susceptibility of the axon to AC neurotoxicity. Two variations of this model were also studied. First, rats given five daily injections of AC (30 mg/kg, IP) beginning one week following IDPN administration developed accumulations of fast axonally transported materials in IDPN-induced microtubule channels. Second, rats given chronic injections of AC (30 mg/kg, IP, five days/week, for four weeks), to reduce the delivery of neurofilaments to the proximal axon, developed less prominent axonal enlargements when challenged with IDPN. Thus, axonal atrophy can mask the development of neurofilamentous axonal swellings.

Acrylamide↗
PubMed1978

Kinetic properties of normal and perturbed axonal transport of serotonin in a single identified axon.

1. The axonal transport of pulses of [3H]serotonin was studied in an axon of the serotonergic giant cerebral neurone (GCN) of Aplysia californica. 2. [3H]serotonin was transported as a discrete peak which was followed by a relatively low, smooth trail. 3. The peak broadened as it moved along the axon, sometimes skewing in the proximal direction. 4. The velocity of the transport was highly dependent on temperature, but the rate of peak broadening was not. The velocity was 130 mm per day at 23 degrees C and 48 mm per day at 14 degrees C. The rate of broadening was 143 micrometer per mm transport at 23 degrees C and 156 micrometer per mm transport at 14 degrees C. 5. In another series of experiments, almost the entire length of the lip nerve, which contained the axon of GCN, was maintained at 1--3 degrees C to block transport. The GCN's cell body and the proximal few millimetres of the nerve were maintained at 23 degrees C. As a result, the amount of [3H]serotonin in the proximal segment of the nerve increased manyfold during periods of up to 4 hr. The concentrated pulse of [3H]serotonin resulting from this treatment was transported more slowly than normal after the cooling was terminated. Sometimes, a minor peak split from the major peak of radioactivity and was transported a normal velocity. 6. Incubation of the cerebral ganglion and nerves for 16 hr in the presence of anisomycin, an inhibitor of protein synthesis, reduced by nearly fourfold the amount of [3H]serotonin subsequently exported into the axon of the GCN. The transport velocity at this reduced concentration was less than half the normal value. If the concentration of [3H]serotonin in the axon was restored to normal in the presence of anisomycin, the velocity of transport was also returned to normal. 7. We conclude that the velocity of transport of serotonergic vesicles in the axon of the GCN is positively dependent on the local concentration of vesicles, except at very high concentrations, where the dependence is negative. The results are interpreted in the context of a model for transport in which the serotonergic vesicle is translocated along the axon in an intermittent fashion, alternating between moving and stationary states. The local concentration of the vesicles along the axon would control the observed velocity of transport by altering the partitioning between the two states, that is, by changing the percentage of time vesicles spend in each state.

Animals↗
PubMed1986

Diversity in the axonal transport of structural proteins: major differences between optic and spinal axons in the rat.

Investigations of slow axonal transport reveal variation in both protein composition and the rate of movement. However, these studies involve a variety of nerve preparations in different species, and most lack the resolution needed to determine the kinetics of identified proteins. We have compared the axonal transport of slow-transported proteins in retinal ganglion cells and spinal motor neurons of young rats. Nine proteins that contribute to axonal structures were examined: the neurofilament triplet (NFT), alpha and beta tubulin, actin, fodrin, calmodulin, and clathrin. Axonally transported proteins were pulse-labeled by intraocular or intracord injections of 35S-methionine. After allowing sufficient time for labeled slow-component proteins to enter the spinal or optic nerves, consecutive 2-3 mm nerve segments were subjected to SDS-PAGE. Fluorographs were used as templates for locating the gel regions containing the above polypeptides, and the radioactivity in these regions was measured by liquid-scintillation spectrometry. In retinal ganglion cells, the peak of tubulin labeling advanced at 0.36 mm/d in association with the NFT and fodrin. The cotransport of tubulin and the NFT identified this complex as the slower subcomponent of slow transport, termed slow component a (SCa) and representing the movement of the microtubule-neurofilament network. The peaks of actin and calmodulin labeling were cotransported at 2.3 mm/d in near-register with peaks of fodrin and clathrin labeling. These 4 proteins, moving ahead of the NFT, identified this complex as SCb--the faster subcomponent of slow transport, which represents the movement of the cytoplasmic matrix and microtrabecular lattice. Both subcomponents had the same composition and rate as that reported for the optic axons of guinea pigs and rabbits, establishing a basic mammalian pattern. In spinal motor axons, the SCa tubulin peak advanced at 1.3 mm/d, and the SCb actin and calmodulin peaks were cotransported at 3.1 mm/d. Unlike optic axons, SCa in motor axons was more heavily labeled than SCb, and included labeled peaks of actin, clathrin, and calmodulin moving in register with the SCa tubulin peak. Actin was the most heavily labeled of these SCb proteins moving with SCa, and it left a higher plateau of radioactivity behind the advancing SCa peak. The SDS-PAGE labeling pattern for SCb did not differ from that seen in optic axons, except that some tubulin was found to form a peak that advanced in register with the actin and calmodulin peaks.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Fast axonal transport in permeabilized lobster giant axons is inhibited by vanadate.

We have developed a method for permeabilizing axons and reactivating the fast transport of microscopically visible organelles. Saltatory movements of organelles in motor axons isolated from lobster walking legs were observed using Nomarski optics and time-lapse video microscopy. In the center of the axon most of the particles and mitochondria moved in the retrograde direction, but immediately below the axolemma the majority moved in the anterograde direction. When axons were permeabilized with 0.02% saponin in an adenosine 5'-triphosphate (ATP)-free "internal" medium, all organelle movement ceased. Saltatory movements resembling those in intact axons immediately reappeared upon the addition of MgATP. Very slight movement could be detected with ATP concentrations as low as 10 microM, and movement appeared to be maximal with 1 to 5 mM ATP. Vanadate, which does not affect axonal transport in intact axons, inhibited the reactivated organelle movements in permeabilized axons. Movement was rapidly and reversibly inhibited by 50 to 100 microM sodium orthovanadate. The effects of vanadate, including the time course of inhibition, its reversibility, and its concentration dependence, are consistent with the hypothesis that a dyneinlike like molecule may play a role in the mechanism of fast axonal transport.

Adenosine Triphosphate↗
PubMed2000

Neuronal morphology, axonal integrity, and axonal regeneration in situ are regulated by cytoskeletal phosphorylation in identified lamprey central neurons.

The CNS of the sea lamprey (Petromyzon marinus) contains giant, individually identifiable neurons that can be microinjected intracellularly in the living animal. We have used the unique accessibility of this system to investigate the role played by serine/threonine kinases and phosphatases in regulating cytoskeletal stability in identified reticulospinal neurons (ABCs) in situ. Injection of broad spectrum kinase and phosphatase inhibitors induce marked changes in ABC gross morphology and in the extent and morphology of sprouts induced by axotomy. The kinase inhibitor K-252a causes regenerating sprouts to be longer and narrower than those seen in control preparations, and significantly reduces the diameters of axon stumps; this latter effect is similar to the effect of microinjecting anti neurofilament (NF) antibodies. By contrast, the phosphatase inhibitor okadaic acid (OA) causes the selective disruption of axonal integrity, blocking axonal regeneration and causing axon stump retraction in axotomized ABCs. The microtubule (MT) disrupting drug colchicine has an effect similar but less marked than OA on ABC axonal morphology. Both OA and colchicine also induce the formation of large somatodendritic swellings in axotomized (but not intact) ABCs by 1-3 weeks post-injection. Immunocytochemical analyses indicate that both colchicine and OA treatments result in the destabilization of MTs and the phosphorylation of NFs, while OA induces the accumulation of phosphorylated tau protein in some dendritic swellings. Control injections of inactive substances have none of these effects. These results suggest that OA does not have its primary effect on NF assembly at the doses used, but may block axonal regeneration by inducing a prolonged disruption of axonal MTs, possibly via an indirect mechanism involving the hyperphosphorylation of tau and other MAPs. K-252a, on the other hand, may interfere with NF assembly and sidearm phosphorylation, thereby reducing NF transport into both axon stumps and sprouts and in turn reducing sprout diameter. The implications of these results for the respective roles of MTs, MAPs, and NFs in axonal regeneration in the vertebrate CNS are discussed.

Animals↗
PubMed1985

Wide-spreading terminal axons in the inner plexiform layer of the cat's retina: evidence for intrinsic axon collaterals of ganglion cells.

Extracellular, iontophoretic injections of horseradish peroxidase (HRP) were made directly into the cat's retina. The retinas were processed with the cobalt-enhanced diaminobenzidine method and prepared as whole-mounts. These retinas reveal HRP-filled axons that extend widely and terminate within the inner plexiform layer. The axons are morphologically distinct from ganglion and amacrine cell dendritic trees that were retrogradely labelled from the same injection sites. The axons are long and straight, approximately 1 micron in diameter, and in some cases can be traced for several millimeters in the inner plexiform layer. Each axon gives rise to many short, terminal branches that extend, on average, 100 microns from the parent axon and bear clusters of boutons. The terminal branches are widely spaced so that the bouton clusters are distributed in small, isolated patches along the length of the axon. Bouton clusters vary in size and contain from two to over 100 loosely arranged boutons. Single boutons are frequently large, up to 3 microns in diameter. In one case a terminal axon was traced to its origin from the parent axon of an HRP-filled ganglion cell. It is suggested, therefore, that these axons are intrinsic to the retina and originate as primary collaterals of ganglion cells.

Animals↗
PubMed1991

Local control of axonal properties by Schwann cells: neurofilaments and axonal transport in homologous and heterologous nerve grafts.

A number of axonal properties, including slow axonal transport and neurofilament phosphorylation, are altered in a mutant mouse strain with a Schwann cell deficiency, the Trembler. The Trembler phenotype is associated with poor myelination and reduced axonal caliber in the peripheral nervous system, but the genetic lesion has not yet been identified. To determine whether changes in axonal properties resulted from a direct action of Schwann cells on the axon, a segment of sciatic nerve from myelin-deficient Trembler mouse was grafted into the sciatic nerve of a normal mouse and normal axons were allowed to regenerate. Normal axons surrounded by Trembler Schwann cells are reduced in diameter, but resume their original diameter distal to the graft. Neurofilament transport was also affected locally in sciatic nerves with Trembler grafts into normal nerve. The velocity of neurofilament transport was not significantly different from controls in portions of the nerve proximal to the Trembler graft, but there was a reduction in neurofilament transport rates upon entering the Trembler graft. This was accompanied by an increase in the ratio of neurofilament over tubulin in the case of the Trembler graft, suggesting both a slowing of the neurofilament and an increase in the rate of tubulin transport. Using heterologous grafts of Trembler nerve segments into wildtype nerves, Schwann cells were shown to locally influence axonal caliber, neurofilament organization, and slow axonal transport. These observations emphasize the importance of glial cells in modulating neuronal structure and functions, as well as focusing attention on the role of glia in the etiology of neuropathologies that alter the neuronal environment.

Animals↗
PubMed1994

Cell adhesion molecule SC1/DMGRASP is expressed on growing axons of retina ganglion cells and is involved in mediating their extension on axons.

We determined expression and function of a cell membrane protein in the developing chick retinotectal system identified by a monoclonal antibody (mAb 4H5) and the corresponding antiserum. Our data revealed that the protein shares a series of properties, including the N-terminal amino acid sequence, with a cell adhesion molecule termed DM-GRASP, SC1, BEN, and JC7. It can therefore be considered identical with this molecule and is referred to as SC1/DMGRASP. In early development of the retinotectal system, SC1/DMGRASP is exclusively expressed on growing, far-projecting, tract-forming axons. Expression begins at the onset of retina ganglion cell axogenesis and its maximum overlaps with the phase of maximal axon extension. Later in development, SC1/DMGRASP appears on distinct laminae within plexiform layers in spatiotemporal correlation with synaptogenesis. In an in vitro assay system designed to study the elongation of RGC axonal processes on preexisting RGC axons, addition of SC1/DMGRASP antiserum specifically reduces lengths of axonal processes. In contrast, axonal growth on laminin or basal lamina preparations is not SC1/DMGRASP-dependent. Taken together, the data provide evidence for a role of SC1/DMGRASP in axonal elongation of SC1/DMGRASP-positive axons on such axons, thereby possibly contributing to the pathway and target finding mechanisms of far-projecting, tract-forming central nervous system neurons.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1990

Relations between axons and oligodendroglial cells during initial myelination. II. The individual axon.

Axo-glial relations in the ventral funiculus of the spinal cord (SC) and in the corpus callosum (CC) of the cat were examined by electron microscopy during initial myelination. In addition to random transverse and longitudinal sections from several stages, two series of sections were studied. As a first step in myelination the axons become ensheathed by one to three uncompacted glial lamellae (E-sheaths). E-sheaths present a length range from less than 5 microns to 149 microns (SC) or to 93 microns (CC). E-sheaths are more frequent along SC-axons than CC-axons, and the mean E-sheath is 3.3-fold longer in the former compared to the latter. In both areas naked axon portions occur between successive E-sheaths, but these gaps are insufficient to allow elongation of all short E-sheaths into long ones. Sheaths composed of mixed compacted (M-sheaths) and uncompacted segments have a length range of 66-212 microns in the SC and 66-171 microns in the CC. In relation to the undifferentiated terminations of E-sheaths or mixed E/M-sheaths, undercoated axolemmal domains are always lacking. Fully compacted sheaths were not found in the series from the SC. In the CC, 141-212 microns long compact sheaths were found, with tight axoglial junctions at their terminations. Axolemmal domains with a 'nodal' undercoating occur in relation to some of these terminations. In both areas, individual developing axons present a chaotic mixture of naked, ensheathed and myelinated portions; bulges with clusters of vesiculotubular profiles are frequent along naked and ensheathed axonal portions, particularly in the SC. The axon diameter is clearly larger in myelinated than in naked portions of the same axon. On the basis of these results, we propose that the early glial sheaths of developing CNS axons actively elongate and undergo extensive remodelling before compaction. The maximal length of uncompacted E-sheaths, and the sheath length at which axoglial junctions and nodes of Ranvier form, are markedly different in the two areas.

Animals↗
PubMed1998

Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments.

The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-D-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15-20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimulation.

Animals↗