Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Axons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed1999

Axon damage and repair in multiple sclerosis.

It is well known that within long-standing multiple sclerosis (MS) lesions there is axonal loss but whether it is an early or late event has been more difficult to establish. The use of immunocytochemical methods that reveal axonal end-bulbs is a valuable approach to investigating acute axonal injury in human pathological material. The application of these techniques to multiple sclerosis tissue reveals evidence of axonal injury in acute lesions; the distribution of the end-bulbs in acute and active-chronic lesions is associated with regions of maximal density of infiltrating macrophages. Axon injury within the MS lesion will result in both Wallerian degeneration of the axon and also retrograde degeneration of the cell body. The functional consequences of the axon injury will depend upon numbers of axons injured and the topographical organization of the fibres coursing through the lesion. The molecular mechanisms by which the recruited leucocytes damage or transect the axons are not known. However, investigations in the Wld mutant mouse with very slow Wallerian degeneration demonstrate that axon degeneration is not simply a passive disintegration of the axon but has clear parallels with the active processes of programmed cell death. The presence of early axon injury and the consequences of an ever increasing load of neuronal damage has important implications not only for when therapy should be initiated in MS but also the therapeutic target.

Animals↗
PubMed1994

Juvenile visual callosal axons in kittens display origin- and fate-related morphology and distribution of arbors.

In kittens, callosal axons originating either from medial area 17 (transient axons) or near the 17/18 border (mostly permanent axons) were labelled with anterogradely transported biocytin; they were reconstructed by computer from serial sections, and their morphologies compared at different ages. During the first and second postnatal weeks both sets of axons branched profusely in the white matter of the lateral gyrus and the number of branches increased with age. The most common type of axon ending was the growth cone; others may have been collapsing growth cones, branches in the process of elimination or early synaptic boutons. Axons from medial area 17 distributed over a broad territory, including the 17/18 border where callosal axons terminate in the adult cat, but without aiming specifically at any one area. The majority of axons and their branches terminated in the white matter or at the bottom of layer VI; exceptionally they extended further into the cortex. Most of the axons originating near the 17/18 border were different from those described above, and the difference increased with age. Although they also terminated profusely in the white matter of the lateral gyrus, most of the branches terminated near the contralateral 17/18 border; they frequently entered the grey matter up to the superficial layers and branched into it. During the third week, axons from medial area 17 were rarely found to extend beyond the corpus callosum, probably because they were in the process of being eliminated. In contrast, axons originating near the 17/18 border had increased their number of branches in the grey matter. In conclusion, during the first and second postnatal weeks axons grew and differentiated according to their origin, and this anticipated whether they would be maintained or eliminated. Neurotrophic signals, possibly from the white matter or the subplate, and growth-inhibiting signals from area 17 may be involved in this process.

Aging↗
PubMed1996

Accurate synapse regeneration despite ablation of the distal axon segment.

In each body ganglion of the leech Hirudo medicinalis there is a single S-cell. After an S-cell axon is severed, it regenerates along its surviving distal segment and reconnects with its synaptic target, the axon of the neighbouring S-cell. In approximately half the cases the regenerating axon forms a temporary electrical synapse specifically with the distal segment, which remains active and connected to the target, thereby functioning as a splice until regeneration is complete. To determine whether the distal axon segment is required for successful regeneration, distal segments of severed S-cell axons were ablated by intracellular injection of bacterial protease. Fifty-seven preparations were examined from 2 to 212 days after injection of the axon segment. The extent of S-cell axon regeneration was assessed electrophysiologically by intracellular and extracellular recording, and anatomically by intracellular injection of markers followed by light microscopy and electron microscopy. The S-cell axons regenerated successfully in almost 90% of animals examined after 2 weeks or more. In a further four animals the target S-cell was ablated in addition to the distal axon segment, permanently disrupting conduction along the S-cell pathway. Nevertheless, the regenerating axon grew along its usual pathway and there was no evidence that alternative connections were formed. It is concluded that, although the distal axon segment can provide a means for rapid functional repair, the segment is not required for reliable regeneration of the axon along its usual pathway and accurate formation of an electrical synapse.

Animals↗
PubMed2005

Membrane-associated guidance cues direct the innervation of forebrain and midbrain by dorsal raphe-derived serotonergic axons.

Unlike many neurons that extend an axon precisely to a single target, individual dorsal raphe 5-HT neurons project to multiple brain regions and their axon terminals often lack classical synaptic specializations. It is not known how 5-HT axon collaterals select between multiple target fields, or even if 5-HT axons require specific guidance cues to innervate their targets. Nor is it known how these axon collaterals are restrained within specific innervation target regions. To investigate this, we challenged explants of dorsal raphe with co-explants, or cell membrane preparations of ventral midbrain, striatum or cerebral cortex. We provide evidence for membrane-associated cues that promote 5-HT axon growth into each of these three target regions. The axon growth-promoting activity was heat-, protease- and phosphatidylinositol-phospholipase-C (PI-PLC)-sensitive. Interestingly, 5-HT axons specifically lost the ability to grow in heterotypic explants, or membrane carpets, following contact with ventral midbrain or striatal, but not cortical, explants or membranes. This inductive activity associated with striatal and ventral midbrain membranes was sensitive to both high salt extraction and PI-PLC treatment. By contrast, the activity that inhibited 5-HT axon growth onto heterotypic membranes was sensitive only to high salt extraction. These results provide evidence that a glycosylphosphatidylinositol (GPI)-linked membrane protein promotes 5-HT axon growth, and that short-range membrane-bound, as well as GPI-linked, molecules contribute to the guidance of 5-HT axon collaterals. These findings suggest that 5-HT axon collaterals acquire a target-induced growth-inhibitory response to alternative targets, increasing their selectivity for the newly innervated field.

Age Factors↗
PubMed1982

Local protein synthesizing activity in axonal fields regenerating in vitro.

The goldfish retinal explant system of Landreth and Agranoff was used to study endogenous protein synthesizing activity of retinal ganglion cell axons regenerating in culture. Light and electron microscopic examination of axonal fields showed that axons were free of nonneural cell investment. Decentralized axons were incubated with a mixture of tritiated amino acids, and direct quantitative microanalysis of protein and tritium radioactivity was carried out on individual axonal fields. Our findings showed that radioactive amino acids were incorporated into axonal protein in a manner that inhibited significantly by cycloheximide, but not by chloramphenicol. Decentralized axons appeared to maintain their viability for at least 3-4 h. Axonal fields maintaining their central connections to the explant incorporated 3H-amino acids at an apparent rate that was similar to decentralized axonal fields. Labeled material transported into axonal fields from ganglion cell bodies appeared in significant amounts after a delay of 2-3 h. Fluorographic patterns of axonal proteins after labeling with either 3H-amino acids or [35S]methionine and separated by microelectrophoresis indicated that primarily tubulin and, to a lesser extent, actin were labeled. Our findings indicate that goldfish retinal ganglion cell axons regenerating in vitro exhibit measureable endogenous protein-synthesizing activity.

Amino Acids↗
PubMed1978

Identification of intrafusal muscle fibres activated by single fusimotor axons and injected with fluorescent dye in cat tenuissimus spindles.

1. Intrafusal muscle fibres of cat tenuissimus spindles have been injected with the fluorescent dye Procion Yellow and identified histologically after recording their changes in membrane potential during 1/sec stimulation of single static or dynamic gamma axons. 2. Thirteen intrafusal muscle fibres innervated by static gamma axons were identified as eight bag2 and five chain fibres. The fact that none proved to be a bag1 fibre is not regarded as significant, for reasons given in the Discussion. 3. In one spindle Procion Yellow was injected into two intrafusal muscle fibres activated by the same static gamma axon; they were identified as a bag2 and a chain fibre. 4. Nine intrafusal muscle fibres innervated by dynamic gamma axons were identified as seven bag1 fibres, one bag2 fibre, and one long chain fibre. 5. In one spindle two bag fibres were injected, one activated by a dynamic gamma axon, the other by a static gamma axon; the former proved to be a bag1 fibre, the latter a bag2 fibre. 6. Stimulation of static gamma axons elicited junctional potentials in seven bag2 fibres and one damaged chain fibre, and action potentials in one bag2 and four chain fibres. In the whole sample of impaled intrafusal muscle fibres (identified and unidentified) activated by static axons, junctional potentials were recorded from twenty-three (62.2%), and action potentials from fourteen (37.8%). Stimulation of dynamic gamma axons always elicited junctional potentials. 7. In a number of instances it was possible to examine the ultrastructure of motor endings belonging to the stimulated gamma axon. The myoneural junctions of trail endings supplied by static gamma axons to bag2 and chain fibres were both smooth and folded; the deepest and most regular folding occurred on chain fibres. The terminals of p2 plates supplied to bag1 fibres by dynamic gamma axons had smooth myoneural junctions.

Action Potentials↗
PubMed1982

Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential.

1. Electrophysiological techniques are described which allow intracellular recording from peripheral myelinated axons of lizards and frogs for up to several hours. The sciatic and intramuscular axons studied here have resting potentials of -60 to -80 mV and action potentials (evoked by stimulation of the proximal nerve trunk) of 50-90 mV. They show a prominent depolarizing afterpotential (d.a.p.), which is present both in isolated axons and in axons still attached to their peripheral terminals. This d.a.p. has a peak amplitude of 5-20 mV at the resting potential, and decays with a half-time of 20-100 msec.2. The peak amplitude of the d.a.p. is voltage-sensitive, increasing to up to 26 mV with membrane hyperpolarization. The d.a.p. disappears as the axon is depolarized to -60 to -45 mV, and does not appear to reverse with further depolarization.3. The d.a.p. is not reduced when bath Ca is replaced by 2-10 mm divalent Mn or Ni. The d.a.p. is not reversed when axons depleted of Cl (by prolonged exposure to Cl-deficient, SO(4)-enriched solutions) are bathed in Cl-rich solutions. These results suggest that the d.a.p. is not mediated by a conductance change specific for Ca or Cl ions. Partial substitution of tetramethylammonium for bath Na, or addition of 10(-5)m-tetrodotoxin to the normal bathing solution, reduces the amplitude of both the action potential and the d.a.p.4. The amplitude of the d.a.p. is not sensitive to bath [K] over the range 1-7.5 mm, provided that all measurements are made at the same holding potential. This result argues that the d.a.p. is not mediated by accumulation of K outside the active axon.5. Treatments expected to inhibit the Na-K exchange pump (cooling from 25 to 10 degrees C, or 0.15 mm-ouabain) do not enlarge or prolong the d.a.p., although they do abolish a slower hyperpolarizing afterpotential seen following repetitive stimulation.6. The passive voltage response of the axon to small injected pulses of depolarizing or hyperpolarizing current shows a prominent, slowly decaying component with a time course similar to that of the d.a.p. Depolarizing current reduces the input resistance of the axon, and increases the rate of decay of both the passive voltage response and the d.a.p. There is a slight conductance increase during the peak of the d.a.p., but the same conductance increase can be produced by a comparable passive depolarization.7. We conclude that the d.a.p. is due mainly to a passive capacitative current, probably resulting from discharge of the internodal axonal membrane capacitance through a resistive current pathway beneath or through the myelin sheath. We suggest that this slow capacitative discharge becomes evident as soon as most of the nodal ionic channels activated during the action potential have closed. An electrical model of the myelinated axon that incorporates the postulated internodal leakage pathway can account both for the prolonged d.a.p. recorded inside the axon, and for the potential profile recorded extra-axonally in or near the internodal periaxonal space.

Action Potentials↗
PubMed2002

Activity-dependent plasticity of calcium clearance from crayfish motor axons.

Previous studies of a crayfish explant culture demonstrated that regenerating motor axons with high impulse activity develop more rapid clearance of cytoplasmic free Ca(2+) than those with low impulse activity. We examined whether Ca(2+) clearance in mature axons also showed activity-dependent plasticity. We studied the phasic and tonic axons of the motor bundle innervating the crayfish closer muscle that display large differences in impulse activity. To compare their Ca(2+) regulation, we applied the Ca(2+) ionophore Br-23187 (1 microM) and measured the increase in intracellular free Ca(2+) concentration ([Ca(2+)](i)) with fura-2. After 55 min of ionophore application, the increase in [Ca(2+)](i) in the phasic axons (1,326 +/- 192 nM) was significantly greater than in the tonic axons (359 +/- 148 nM). This resulted from stronger Ca(2+) clearance in the tonic axon rather than less Ca(2+) influx because blocking Ca(2+) clearance by Na/Ca exchange and mitochondria eliminated these differences in [Ca(2+)](i). Next we determined whether Ca(2+) clearance from the phasic axon could be strengthened by a prolonged increase in impulse activity. The phasic axon was stimulated in vivo at 5 Hz for 1 h/day for 5 days, and 1-3 days after stimulation, Ca(2+) clearance was again examined. After 55 min of Br-23187 (1 microM) exposure, the increase in [Ca(2+)](i) in the stimulated phasic axon was only 232 plus minus 123 nM, which was much less than in the control phasic axons and similar to that in the tonic axons. Thus Ca(2+)-clearance mechanisms adapt to changes in impulse activity both in growing and mature axons.

Animals↗
PubMed1985

Axonal projection patterns of ventrolateral medullospinal sympathoexcitatory neurons.

We studied the following properties of cat ventrolateral medullary (VLM) neurons that projected to the thoracic spinal cord: the relationship between their spontaneous activity and that in the inferior cardiac postganglionic sympathetic nerve, their responses to baroreceptor-reflex activation, their axonal conduction velocities, the funicular trajectories of their axons, the likely sites of termination of their axons, and their axonal branching patterns. Microstimulation in the second thoracic spinal segment (T2) antidromically activated 67 VLM neurons (as determined with time-controlled collision of spontaneous and evoked action potentials), whose activity was correlated to inferior cardiac sympathetic nerve discharge (as determined with spike-triggered averaging). We tested the effect of baroreceptor-reflex activation on the firing rate of 20 of these VLM-spinal neurons. Because the firing rate decreased in each instance, these neurons apparently subserved a sympathoexcitatory function. The axonal branching patterns of 51 VLM-spinal sympathoexcitatory neurons were studied. Thirty-four neurons were antidromically activated by stimulation in the T2 gray matter and in more caudal thoracic spinal segments (T11 and/or T6). In each case, the antidromic response evoked by stimulation in the T2 gray matter was due to activation of an axonal branch rather than the main axon (via current spread to the white matter). This was demonstrated with tests that included time-controlled collision of the action potentials initiated by stimulation in T2 and a more caudal thoracic spinal segment. Some VLM-spinal axons that projected to T11 branched in T6 as well as in T2. These data indicate that some VLM-spinal neurons exerted widespread excitatory influences on sympathetic outflow. Seventeen VLM sympathoexcitatory neurons that innervated the T2 gray matter could not be antidromically activated by stimulation in T5, T6, and T11 despite an extensive search at each level. Thus the axonal projections of some VLM-spinal neurons were restricted to upper thoracic segments. Antidromic mapping in T2 revealed that the axons of VLM sympathoexcitatory neurons coursed through the dorsolateral or ventrolateral funiculus to innervate the region of the intermediolateral nucleus. Mean axonal conduction velocity was 3.5 +/- 0.3 m/s. Those VLM-spinal axons restricted to upper thoracic segments generally were located dorsally and/or medially to those that innervated widely separated thoracic segments. The discharges of 35 other VLM neurons that were antidromically activated by T2 stimulation were not related to sympathetic nerve activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Axonal projections of single bulbospinal inspiratory neurons revealed by spike-triggered averaging and antidromic activation.

Activity was recorded extracellularly from 26 inspiratory bulbospinal neurons in anesthetized, paralyzed, artificially ventilated cats. All but one were located in the ventral respiratory group. A neuron was classified as either I alpha or I beta by comparing its firing pattern during inspiratory cycles with lung inflation to its pattern when lung inflation was withheld during the central inspiratory phase (2, 14, 15). In this study, the projection and conduction velocity of these axons were determined using two methods: antidromic activation (AA) of the bulbospinal neurons and spike-triggered averaging (STA) of the extracellular field potentials. These methods have been compared directly because the same electrode was used both for stimulating the axon of the bulbospinal neuron and recording its axonal potential in the same location. Axonal projections from these neurons were mapped in the contralateral spinal cord with a mobile electrode by determining where the lowest stimulus threshold occurs for AA and greatest axonal potential can be recorded with STA. The locations of these axons were in the ventral and lateral funiculi. Each method determined a similar location for an axon. Positions of 10 axons were determined at both the third (C3) and fourth (C4) cervical segments. Single axons maintained their positions in either descending tract from rostral C3 to mid-C4. In five of six cases where two "neighboring" medullary units were characterized, the axons of each pair projected together within 350 micron of each other in the cervical spinal cord. Estimates of mean axonal conduction velocity (CV) from antidromic activation from a single stimulus site, "single-point AA," were as much as 42% less than corresponding estimates from STA extracellular field potentials at that point (P less than 0.001). Such single-point estimates were less than determinations that were calculated from the difference in conduction time and the difference in conduction distance from two points in the spinal cord. These two-point determinations averaged 55.4 +/- 13.1 m/s (using AA) and 53.3 +/- 13.1 (using STA) for 10 neurons. These values were not significantly (P greater than 0.2) different from each other and are greater than most earlier reports, which used the single-point AA method. Either method, AA or STA, can be used to determine axonal position and CV. The advantages and disadvantages of each method are discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Axons crossing in the ventral commissure express L1 and GAD65 in the developing rat spinal cord.

The neural cell adhesion molecule, L1, is thought to play a critical role in the formation and fasciculation of axon tracts during development. In the chick, the L1 cell adhesion molecule is expressed on both ipsi- and contralateral portions of commissural axons and perturbation studies produced a defasciculation of the ipsilateral commissural fibers. Yet in the rat, L1 is reported along commissural axons only after they have reached the contralateral marginal zone. When this species variation was reexamined, L1 was found to be expressed on rat commissural axons in a pattern similar to that observed in the chick. In addition, L1 is detected along commissural axons as early as embryonic day 12 in rats and maintained on both the ipsi- and contralateral surfaces during embryonic development. Other molecular markers that identify commissural axons in rats are TAG-1 (transiently expressed axonal glycoprotein) and DCC (deleted in colorectal cancer), and thus the pattern of L1 staining was compared with that of these other members of the immunoglobulin superfamily. Commissural axons emerging from dorsally located neurons are identified with TAG-1 and DCC, whereas L1 is detected only on ventrally located commissural axons. The pattern of L1 expression overlaps that of the more numerous laterally and ventromedially located GABAergic commissural axons. Furthermore, some of the GABAergic commissural axons express L1 on their surfaces. While commissural axons are often considered as a single population, differences in the combination of adhesion-type molecules on their surfaces and in their neurotransmitter phenotypes may signify distinctive neuronal subgroups.

Animals↗
PubMed2003

Extracellular cues and pioneers act together to guide axons in the ventral cord of C. elegans.

The ventral cord is the major longitudinal axon tract in C. elegans containing essential components of the motor circuit. Previous studies have shown that axons grow out sequentially and that there is a single pioneer for the right axon tract which is important for the correct outgrowth of follower axons. Here, the dependencies between early and late outgrowing axons in the ventral cord were studied systematically with laser ablation experiments and a detailed analysis of mutants using multi-color GFP markers. Different classes of axon were affected to a different extent when the AVG pioneer neuron was eliminated. In the majority of the animals, axons were able to grow out normally even in the absence of the pioneer, suggesting that its presence is not absolutely essential for the correct outgrowth of follower axons. The transcription factor LIN-11 was found to be essential for the differentiation and pioneering function of the AVG neuron. UNC-30 appears to play a similar role for the PVP pioneer neurons. Later outgrowing axons typically do not simply follow earlier outgrowing ones, but subtle dependencies between certain groups of early and late outgrowing axons do exist. Different groups of axons growing in the same axon bundle apparently use different combinations of guidance cues for their navigation and can navigate largely independently.

Animals↗
PubMed2006

Survival motor neuron function in motor axons is independent of functions required for small nuclear ribonucleoprotein biogenesis.

Spinal muscular atrophy (SMA) is a motor neuron degenerative disease caused by low levels of the survival motor neuron (SMN) protein and is linked to mutations or loss of SMN1 and retention of SMN2. How low levels of SMN cause SMA is unclear. SMN functions in small nuclear ribonucleoprotein (snRNP) biogenesis, but recent studies indicate that SMN may also function in axons. We showed previously that decreasing Smn levels in zebrafish using morpholinos (MO) results in motor axon defects. To determine how Smn functions in motor axon outgrowth, we coinjected smn MO with various human SMN RNAs and assayed the effect on motor axons. Wild-type SMN rescues motor axon defects caused by Smn reduction in zebrafish. Consistent with these defects playing a role in SMA, SMN lacking exon 7, the predominant form from the SMN2 gene, and human SMA mutations do not rescue defective motor axons. Moreover, the severity of the motor axon defects correlates with decreased longevity. We also show that a conserved region in SMN exon 7, QNQKE, is critical for motor axon outgrowth. To address the function of SMN important for motor axon outgrowth, we determined the ability of different SMN forms to oligomerization and bind Sm protein, functions required for snRNP biogenesis. We identified mutations that failed to rescue motor axon defects but retained snRNP function. Thus, we have dissociated the snRNP function of SMN from its function in motor axons. These data indicate that SMN has a novel function in motor axons that is relevant to SMA and is independent of snRNP biosynthesis.

Amino Acid Sequence↗
PubMed2005

Plexin-a4 mediates axon-repulsive activities of both secreted and transmembrane semaphorins and plays roles in nerve fiber guidance.

It has been proposed that four members of the plexin A subfamily (plexin-As; plexin-A1, -A2, -A3, and -A4) and two neuropilins (neuropilin-1 and neuropilin-2) form complexes and serve as receptors for class 3 secreted semaphorins (Semas), potent neural chemorepellents. The roles of given plexin-As in semaphorin signaling and axon guidance, however, are mostly unknown. Here, to elucidate functions of plexin-A4 in semaphorin signaling and axon guidance events in vivo, we generated plexin-A4 null mutant mice by targeted disruption of the plexin-A4 gene. Plexin-A4 mutant mice were defective in the trajectory and projection of peripheral sensory axons and sympathetic ganglion (SG) axons and the formation of the anterior commissure and the barrels. The defects in peripheral sensory and SG axons were fundamentally related to those of neuropilin-1 or Sema3A mutant embryos reported but were more moderate than the phenotype in these mutants. The growth cone collapse assay showed that dorsal root ganglion axons and SG axons of plexin-A4 mutant embryos partially lost their responsiveness to Sema3A. These results suggest that plexin-A4 plays roles in the propagation of Sema3A activities and regulation of axon guidance and that other members of the plexin-A subfamily are also involved in the propagation of Sema3A activities. Plexin-A4-deficient SG axons did not lose their responsiveness to Sema3F, suggesting that plexin-A4 serves as a Sema3A-specific receptor, at least in SG axons. In addition, the present study showed that plexin-A4 bound class 6 transmembrane semaphorins, Sema6A and Sema6B, and mediated their axon-repulsive activities, independently of neuropilin-1. Our results imply that plexin-A4 mediates multiple semaphorin signals and regulates axon guidance in vivo.

Animals↗
PubMed2004

Netrin-1 and semaphorin 3A promote or inhibit cortical axon branching, respectively, by reorganization of the cytoskeleton.

In many CNS pathways, target innervation occurs by axon branching rather than extension of the primary growth cone into targets. To investigate mechanisms of branch formation, we studied the effects of attractive and inhibitory guidance cues on cortical axon branching. We found that netrin-1, which attracts cortical axons, and FGF-2 increased branching by >50%, whereas semaphorin 3A (Sema3A), which repels cortical axons, inhibited branching by 50%. Importantly, none of the factors affected axon length significantly. The increase in branching by FGF-2 and the inhibition of branching by Sema3A were mediated by opposing effects on the growth cone (expansion vs collapse) and on the cytoskeleton. FGF-2 increased actin polymerization and formation of microtubule loops in growth cones over many hours, whereas Sema3A depolymerized actin filaments, attenuated microtubule dynamics, and collapsed microtubule arrays within minutes. Netrin-1 promoted rapid axon branching, often without involving the growth cone. Branches formed de novo on the axon shaft within 30 min after local application of netrin-1, which induced rapid accumulation of actin filaments in filopodia. Importantly, increased actin polymerization and microtubule dynamics were necessary for axon branching to occur. Taken together, these results show that guidance factors influence the organization and dynamics of the cytoskeleton at the growth cone and the axon shaft to promote or inhibit axon branching. Independent of axon outgrowth, axon branching in response to guidance cues can occur over different time courses by different cellular mechanisms.

Actins↗
PubMed2002

Reorganization of exuberant axonal arbors contributes to the development of laminar specificity in ferret visual cortex.

Layer-specific cortical axons are believed to develop precisely from the outset without making exuberant branches in incorrect cortical layers. We tested this hypothesis by following the development of axonal arbors of layer 2/3 pyramidal neurons in ferret visual cortex, which in the adult have dense axonal arbors in layers 2/3 and 5 and not in layer 4. We began our studies at earlier ages and sampled at closer intervals than in previous studies. Our studies reveal that between postnatal day (P) 14 and P18 the initial growth of axonal arbors lacks specificity for layers 2/3 and 5 and involves the formation of a small number of branches incorrectly in layer 4. After P18 the number of incorrect axonal branches in layer 4 decreased, whereas there was extensive axonal growth specifically in layers 2/3 and 5. To further study the mechanisms involved in directing the layer-specific growth and elimination of axonal branches, we studied the development of layer 2/3 neurons in slices kept in culture for 5 d. In these studies the initial imprecise growth at P14-18 followed by precise growth after P18 was mimicked in vitro, but the elimination of incorrect axons from layer 4 did not occur. These studies reveal that most axonal arbors grow precisely in the correct layers, but the initial growth involves the formation of a small number of incorrect axonal branches that are later eliminated. Therefore the mechanisms that regulate axonal growth are not as precise initially as later, and mechanisms must exist to allow selective elimination of axon collaterals from incorrect layers.

Animals↗
PubMed1999

Typology, early differentiation, and exuberant growth of a set of cortical axons.

The corpus callosum interconnects both corresponding (homotopic) and noncorresponding (heterotopic) cortical sites of the two hemispheres. We have studied the axons that establish heterotopic connections from visual areas 17 and 18 (E axons) by using anterogradely transported biocytin and three-dimensional serial reconstructions in adult cats and in kittens. Their site of termination distinguished four types of axons. Type EI ends near the border between areas 19/21a or 7, and type EII near the PMLS/PLLS border (posteromedial and posterolateral lateral suprasylvian areas). Type EIII and EIV terminate the first near the PMLS/PLLS and PMLS/21a borders, and the second near the PMLS/PLLS and 19/21a or 7 borders. Taking into account the previously studied homotopic axons (O axons; Houzel et al. [1994] Eur. J. Neurosci. 6:898-917), it can be concluded that areas 17 and 18 are interhemispherically connected by at least five types of axons, three of which (O, EI, and EII) terminate near one areal border, the other two (types EIII and EIV), near two areal borders. All types terminate near representations of the vertical meridian of the visual field. The different types of axons can be identified already during the first postnatal week; at this age, unlike in the adult, they originate not only near the 17/18 border, but also, transiently, in area 17. This suggests that the developing cortex contains sets of neurons destined to send their axon to different targets; however, the axons grow beyond their sites of adult termination. Indeed, exuberant growth takes place at the stage of axonal elongation, and at subsequent stages of axonal differentiation, i.e., during subcortical branching, intracortical branching and synaptogenesis. The growth is progressively more constrained in its topographic distribution and the axons are subsequently reshaped by regressive events.

Aging↗
PubMed1999

Development of a glia-rich axon-sorting zone in the olfactory pathway of the moth Manduca sexta.

Olfactory receptor cells (ORCs) of a particular odor tuning are dispersed in the olfactory epithelium, but their axons converge on distinct glomeruli in primary olfactory centers. As a consequence, axon associations must change to bring axons of ORCs with the same odor specificity together. Studies in Manduca sexta have indicated that just before they enter the antennal lobe (AL), ORC axons undergo extreme reorganization, finally entering the AL in fascicles destined for subsets of glomeruli. This axon-sorting zone is heavily populated by glial cells, and ORC axon growth cones often are in close physical contact with the glia. In moths rendered glia deficient, ORC axons fail to fasciculate in this region. Using propidium iodide to label nuclei and 5-bromo-2'-deoxyuridine to monitor proliferation, we found that the glia in the sorting zone arise from the AL, appearing shortly after the first ORC axons arrive. Experimental removal of some or all of the sensory innervation revealed that proliferation of sorting-zone glia is triggered by ORC axons. A second set of glia arises in the antenna and migrates along the antennal nerve toward the brain, populating the nerve after the establishment of the sorting zone. Development of this type of glial cell is independent of contact of the ORC axons with their central targets. We conclude that the sorting zone arises from CNS glia in response to ingrowth of ORC axons, and a critical number of glia must be present in the sorting zone for axons to correctly establish new neighbor-neighbor associations.

Aging↗