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PubMed1985

Localization and axonal transport of immunoreactive cholinergic organelles in rat motor neurons--an immunofluorescent study.

Antisera produced in rabbits against pure fractions of cholinergic vesicles from Narcine brasiliensis were used to study cholinergic organelles in rat motor neurons. The indirect immunofluorescence method was used on perfusion-fixed material. The rats were surgically sympathectomized to remove sympathetic adrenergic and cholinergic nerves from the sciatic nerve. In the intact animal immunoreactive material, likely to represent cholinergic vesicles, was observed in motor endplates, identified by labelling with rhodamine-conjugated alpha-bungarotoxin or with subsequent acetylcholinesterase staining. The motor perikarya contained very little immunoreactive material. Non-terminal axons were virtually devoid of immunofluorescence in the intact animal. After crushing the sciatic nerve, immunoreactive material (likely to represent axonal cholinergic organelles) accumulated rapidly on both sides of the crush, indicating a rapid bidirectional transport. The transport was sensitive to local application of mitotic inhibitors. The axons which accumulated immunoreactive organelles were motor axons, as demonstrated by various procedures: Cutting of ventral roots prevented accumulation of immunoreactive material in the nerve. Deafferentation did not notably influence accumulations of immunoreactive material. Ligated axons with immunoreactive material were acetylcholinesterase positive when identification was made on the same section; the intra-axonal distribution of immunoreactive material and acetylcholinesterase was not identical, however, and the Narcine antisera did not cross-react with bovine acetylcholinesterase in a solid phase immunoassay. Most axons in ventral roots, but not in dorsal roots, accumulated strongly fluorescent immunoreactive material, while axons in dorsal roots contained weakly fluorescent material. On the other hand, substance P-like immune reactivity was present in many dorsal root axons, but only very rarely in ventral roots. It is suggested that the antisera against Narcine cholinergic vesicles can be used as a marker for cholinergic organelles in the motor neuron, and may be an important tool for studying the axonal cholinergic vesicles. It cannot, however, be used to identify cholinergic structures in unknown locations because it recognizes common antigenic determinants in transmitter organelles of other nerves, e.g. adrenergic nerves. The axonal cholinergic organelles may carry important molecules, other than acetylcholine to the nerve endings.

Animals↗

PubMed1986

Morphometric analysis of experimental spinal cord injury in the cat: the relation of injury intensity to survival of myelinated axons.

The pattern of axonal destruction and demyelination that occurs in experimental contusion injury of cat thoracic spinal cord was studied by line sampling of axons in 1 micron thick plastic sections with the light microscope. Injuries were produced by a weight-drop apparatus, with the vertebral body (T9) below the impact stabilized by supports under the transverse processes. The effects of two combinations of weight and height were examined: 10 or 13 g dropped 20 cm onto an impact area of 5 mm diameter. Animals were kept for 3-5 months after injury, then fixed by perfusion for histological analysis. The number of surviving myelinated axons was found to vary both with the weight used and with the size of the spinal cord. A measure of impact intensity was derived from the calculated momentum of the weight at impact divided by the cross sectional area of the cord (interpolated from dimensions measured rostral and caudal of the lesion following fixation). At impact intensities greater than 0.02 kg-m/s/cm2 there was practically no survival of axons at the center of the injury site, combined with almost complete breakdown of the pial margin. Between 0.08 and 0.2 kg-m/s/cm2 the number of surviving axons varied between 100,000 and 2,000, approximating a negative exponential function (r = -0.88). The number of axons surviving in the outer 100 microns of the cord varied practically linearly (r = -0.82) between near normal and less than 1% of normal over the same range of injury intensity. The number of surviving axons decreased with depth from the pia, also approximating a negative exponential function, with a 10-fold decrease in density over approximately 500 microns. The average slope of this relation with depth remained similar over the range of injury intensity examined, though the slope appeared inversely related to variation in axonal survival for different individuals at a given intensity. It is argued that the loss of axons is probably determined primarily by mechanical stretch at the time of impact. Its centrifugal pattern may be explained by longitudinal displacement of the central contents of the cord, reflecting the viscoelastic "boundary layer" properties of parenchymal flow within the meningeal tube. This is illustrated with reference to the behavior of a gelatin model under compression. The preferential loss of large caliber axons and the characteristic shift to abnormally thin myelin sheaths (resulting from post-traumatic demyelination) both varied in extent independently of injury intensity and overall axonal survival.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Axonal transport of 16S acetylcholinesterase is increased in regenerating peripheral nerve in guinea-pig, but not in rat.

The axonal transport of the molecular forms of acetylcholinesterase was investigated in regenerating facial nerves of guinea-pig and rat. Four forms were separated by velocity sedimentation corresponding to 16S (A12), 10S (G4), 6S (G2) and 4S (G1) acetylcholinesterase. They displayed species-specific changes, which are in good accordance with those previously found in the neuronal perikarya. In the rat, axonal transport decreased for all forms. In the guinea-pig, however, the molecular forms showed differential changes. Whereas after transection, the nerve content of 10S acetylcholinesterase decreased, 16S activity was considerably increased. Anterograde transport of 16S acetylcholinesterase was found to be enhanced, whilst transport of the 10S from decreased. The two lighter forms showed only minor changes. Similar results were obtained for the guinea-pig sciatic nerve. Changes in the localization of acetylcholinesterase activity were investigated by electron microscopical cytochemistry. In the normal facial nerve of both species, activity was located intra-axonally in tubular membraneous structures and on the outer surface of the axonal membrane. In the regenerating facial nerve of the rat, intra-axonal as well as axolemmal activity decreased. Axonal sprouts at the end of the proximal nerve stump showed no activity. In the guinea-pig, however, activity of the axonal membrane increased. This was especially prominent on the surface of axonal sprouts. Strong activity was found also in the extracellular space between the sprouting axons and in the endoneurial space filled by collagen fibres. Biochemical analysis of this region revealed that the histochemical activity was mainly due to the A12 form. Thus it was concluded that, in the guinea-pig, axonal sprouts represent a target for axonally transported A12 acetylcholinesterase, which may also be secreted to extracellular sites.

Acetylcholinesterase↗

PubMed1989

Distinct morphologic classes of serotonergic axons in primates exhibit differential vulnerability to the psychotropic drug 3,4-methylenedioxymethamphetamine.

Immunohistochemical methods were used to analyse the distribution and morphology of serotonergic axons in normal macaque monkeys and in monkeys given (+/-)3,4-methylenedioxymethamphetamine. In untreated monkeys, we observed two morphologic classes of serotonergic axon terminals, which differ in regional and laminar distribution. These two axon types, fine and beaded, correspond to the serotonergic axon types which have been described in the rat. In 3,4-methylenedioxymethamphetamine-treated monkeys, there is a profound loss of serotonergic axon terminals, yet some are consistently spared. The surviving axon terminals are nearly all of the beaded type; in contrast, fine serotonergic axons are markedly reduced in density. There are regional differences in the magnitude of denervation, which reflect differences in the distribution of these two types of serotonergic axons in controls. The present study demonstrates that 3,4-methylenedioxymethamphetamine has differential neurotoxic effects on fine and beaded serotonergic axons. These results indicate that in the primate there are two distinct classes of serotonergic axon terminals, which differ in morphology, distribution, and vulnerability to psychotropic drugs. We hypothesize that in the primate, as demonstrated in the rat, these two classes of serotonergic axon terminals may arise from different raphe nuclei. In both rodent and primate, the dorsal and median raphe nuclei give rise to parallel ascending serotonergic projections, which are likely to have different pharmacologic properties and functions.

3,4-Methylenedioxyamphetamine↗

PubMed1996

Expression of a developmentally regulated, phosphorylated isoform of microtubule-associated protein 1B in regenerating axons of the sciatic nerve.

Monoclonal antibodies SMI-31 and 150 recognize phosphorylation epitopes on microtubule-associated protein 1B that have been shown to be developmentally down-regulated in the nervous system. We have used these antibodies to establish changes in the pattern of expression of their epitopes on microtubule-associated protein 1B in regenerating axons of the sciatic nerves in the adult mouse and rat. Immunohistochemical studies showed that, in the sciatic nerve, regenerating axons in both adult mice and rats were labelled with monoclonal antibody 150 in a proximodistal gradient which was highest at the growth cone. This is the first report of expression of a developmentally regulated, phosphorylated isoform of microtubule-associated protein 1B in regenerating axons. Immunoblotting showed that the expression of the isoform recognized by monoclonal antibody 150 is present in normal adult mouse sciatic nerve and in regenerating axons following crush or cut lesions, but was not detectable in the normal or regenerating adult rat peripheral nervous system. Regenerating axons were also labelled by monoclonal antibody SMI-31, but the labelling, unlike antibody 150 labelling, was uniform along the entire length of the axon and immunoblotting showed that it was due to recognition of neurofilament protein. We conclude that the phosphorylated isoforms of microtubule-associated protein 1B recognized by monoclonal antibody 150 that are developmentally down-regulated in the adult rat central and peripheral nervous systems and adult mouse cerebellum are maintained in the normal peripheral nervous system of the adult mouse. When peripheral axons regenerate in the adult mouse, the regenerating axons also contain these isoforms. Adult rat regenerating axons are stained by antibody 150 only in tissue sections, not in immunoblots. The maintenance of immature isoforms of microtubule-associated protein 1B in mouse peripheral axons may relate to a continual capacity for growth and remodelling. The immunohistochemical localization of the antibody 150 epitope in growth cone-like structures and sprouts in injured nerves shows that phosphorylation of microtubule-associated protein 1B is likely to be an integral part of the regenerative response. These results also show that the phosphorylation epitopes on microtubule-associated protein 1B recognized by monoclonal antibodies 150 and SMI-31 are different and that only expression of the former correlates with axonal regeneration.

Animals↗

PubMed2004

Opposite morphological responses of partially denervated cortical serotonergic and noradrenergic axons to repeated stress in adult rats.

We examined plastic changes in serotonin (5-HT) axons following repeated stress in the adult rat brain, and compared stress-induced changes between 5-HT and noradrenaline (NA) axons. We locally injected the specific neurotoxin to 5-HT axons or to NA axons into the frontal cortex to cause partial denervation. The animals were mildly restrained from 1 day after the neurotoxin injection and this stress was repeated daily for 20 min during the first 2 days and for 40 min during the next 11 days. On the fourteenth day after injection, the brains were removed to visualize 5-HT and NA axons by immunohistochemistry. Repeated stress did not significantly alter the denervation area of 5-HT or NA axons, but the density of 5-HT axons was increased whereas that of NA axons was decreased in cortical regions outside the denervation site. In addition, the expression of brain-derived neurotrophic factor (BDNF) was increased in cortical regions where the 5-HT axon density was increased in response to stress. These results suggest that repeated stress causes opposite changes in the morphology of partially denervated 5-HT and NA axons in the cerebral cortex. The stress-induced increase in BDNF expression may contribute to 5-HT axon sprouting following repeated stress.

5,6-Dihydroxytryptamine↗

PubMed2004

Axonal dystrophy of dorsal root ganglion sensory neurons in a mouse model of Niemann-Pick disease type C.

Niemann-Pick disease type C (NP-C) is a progressive and fatal neurological disorder characterized by intracellular accumulation of cholesterol and glycolipid. A Balb/c-npc1 mutant strain is a genetically authentic murine model of NP-C, and homozygous mice show progressive weight loss and tremor or ataxia until death at 12-14 weeks of age. Neuropathologically, this model is known to faithfully reproduce the cardinal histologic features of NP-C including neuronal storage, appearance of swollen axons (spheroids), and neuronal loss, although the cellular mechanisms of neural degeneration are largely unknown. To investigate the mode of neural degeneration of sensory neurons in NP-C, we studied the central processes of dorsal root ganglion (DRG) neurons at the level of the medullary dorsal column nuclei and the spinal dorsal horn with special attention to the ultrastructural changes of presynaptic axon terminals. The appearance of axonal spheroids in the dorsal column nuclei and the loss of axons in the spinal nerve roots were assessed quantitatively. We show that the gracile nuclei develop numerous axonal spheroids after only 3 weeks. At 6 and 9 weeks, dystrophic axons, which were separated from simple axonal spheroids by the ultrastructural presence of distinctive tubulo-vesicular elements, progressively increased in size and number. These neuropathological findings are identical to those of gracile axonal dystrophy (GAD) of the normal aging mouse. Presynaptic elements were exclusively involved in spheroid formation. The cuneate nuclei and the spinal dorsal horn revealed fewer axonal spheroids and only rare dystrophic changes. This was associated with a significant drop in the number of L4-5 dorsal root axons in NP-C mouse at 9 weeks of age compared with controls. These results support the existence of a length-dependent axonopathy in the central processes of DRG neurons and are consistent with the view that altered axonal transport, which is implicated in the pathogenesis of GAD in physiological aging, may be an underlying mechanism in neuronal degeneration in NP-C. Clinically, the premature development of GAD may be responsible for ataxia, one of the early manifestations of this disease.

Age Factors↗

PubMed2003

The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways.

Invading meningeal cells form a barrier to axon regeneration after damage to the spinal cord and other parts of the CNS, axons stopping at the interface between meningeal cells and astrocytes. Axon behavior was examined using an in vitro model of astrocyte/meningeal cell interfaces, created by plating aggregates of astrocytes and meningeal cells onto coverslips. At these interfaces growth of dorsal root ganglion axons attempting to grow from astrocytes to meningeal cells was blocked, but axons grew rapidly from meningeal cells onto astrocytes. Meningeal cells were examined for expression of axon growth inhibitory molecules, and found to express NG2, versican, and semaphorins 3A and 3C. Astrocytes express growth promoting molecules, including N-Cadherin, laminin, fibronectin, and tenascin-C. We treated cultures in various ways to attempt to promote axon growth across the inhibitory boundaries. Blockade of NG2 with antibody and blockade of neuropilin 2 but not neuropilin 1 both promoted axon growth from astrocytes to meningeal cells. Blockade of permissive molecules on astrocytes with N-Cadherin blocking peptide or anti beta-1 integrin had no effect. Manipulation of axonal signalling pathways also increased axon growth from astrocytes to meningeal cells. Increasing cAMP levels and inactivation of rho were both effective when the cultures were fixed in paraformaldehyde, demonstrating that their effect is on axons and not via effects on the glial cells.

Animals↗

PubMed2004

Tenascin-R as a repellent guidance molecule for newly growing and regenerating optic axons in adult zebrafish.

In adult fish, in contrast to mammals, new optic axons are continuously added to the optic projection, and optic axons regrow after injury. Thus, pathfinding of optic axons during development, adult growth, and adult regeneration may rely on the same guidance cues. We have shown that tenascin-R, a component of the extracellular matrix, borders the optic pathway in developing zebrafish and acts as a repellent guidance molecule for optic axons. Here we analyze tenascin-R expression patterns along the unlesioned and lesioned optic pathway of adult zebrafish and test the influence of tenascin-R on growing optic axons of adult fish in vitro. Within intraretinal fascicles of optic axons and in the optic nerve, newly added optic axons grow in a tenascin-R immunonegative pathway, which is bordered by tenascin-R immunoreactivity. In the brain, tenascin-R expression domains in the ventral diencephalon, in non-retinorecipient pretectal nuclei and in some tectal layers closely border the optic pathway in unlesioned animals and during axon regrowth. We mimicked these boundary situations with a sharp substrate border of tenascin-R in vitro. Optic axons emanating from adult retinal explants were repelled by tenascin-R substrate borders. This is consistent with a function of tenascin-R as a repellent guidance molecule in boundaries for adult optic axons. Thus, tenascin-R may guide newly added and regenerating optic axons by a contact-repellent mechanism in the optic pathway of adult fish.

Animals↗

PubMed1998

Cellular and molecular correlates of the regeneration of adult mammalian CNS axons into peripheral nerve grafts.

Studies of the regeneration of CNS axons into peripheral nerve grafts have provided information crucial to our understanding of the regenerative potential of CNS neurons. Injured axons in the thalamus and corpus striatum produce regenerative sprouts within a few days of graft implantation, apparently in response to living cells in the grafts. The regenerating axons often grow directly towards the grafts, and enter Schwann cell columns where they elongate surrounded by Schwann cell processes. The regenerating CNS axons, and the Schwann cell processes along which they grow, initially express the cell adhesion molecules NCAM, and L1. The axons also express polysialic acid and, unlike regenerating peripheral axons, bind tenascin-C derived from Schwann cells. Wherever peripheral nerve grafts are implanted into the CNS they appear to promote the differential regeneration of CNS axons. Most of the axons which grow into grafts in the thalamus are derived from the thalamic reticular nucleus (TRN), whereas grafts in the striatum promote regeneration of axons from the substantia nigra pars compacta (SNpc) and grafts in the cerebellum promote regeneration from deep cerebellar nuclei (DCN) and brainstem precerebellar neurons. In contrast most thalamocortical projection neurons, striatal projection neurons and Purkinje cells in the cerebellar cortex are poor at regenerating. There are patterns to the expression of regeneration-related molecules by axons injured by nerve grafts in the CNS. Most neurons which regenerate well (e.g. TRN and DCN neurons) upregulate GAP-43, L1 and the transcription factor c-jun in response to a graft, whereas those neurons which do not regenerate well (e.g. Purkinje cells, thalamocortical and striatal projection neurons) do not upregulate these molecules. These observations suggest that some classes of CNS neurons may be intrinsically unable to regenerate axons and the repair of injuries in the brain and spinal cord may consequently require some form of gene therapy for axotomised neurons.

Animals↗

PubMed1993

Pathobiology of traumatically induced axonal injury in animals and man.

STUDY OBJECTIVES: Although diffuse axonal injury is recognized as a consistent feature of traumatic brain injury, there is confusion regarding its pathogenesis. To provide insight into its pathogenesis, animal models of traumatic brain injury complemented by post mortem human analyses were used. DESIGN: In animals, anterograde tracers together with antibodies targeting the neurofilament subunits were used in light and electron microscopic analyses of axonal injury. In humans, antibodies to the neurofilament subunits also were used to follow diffuse axonal injury. Animals were followed from minutes to months after injury, whereas humans were studied from six hours to 59 days after injury. MEASUREMENTS AND MAIN RESULTS: In neither animals nor humans did traumatic brain injury cause direct axonal tearing. Instead, the traumatic brain injury triggered focal intra-axonal change in the 68-kd neurofilament subunit, which became disordered in its alignment and resulted in impaired axoplasmic transport. This caused axonal swelling and disconnection. The sequence of axonal change was similar in animals and man; however, its temporal progression was slower in humans. CONCLUSION: Traumatically induced axonal damage is triggered first by focal intra-axonal change involving the neurofilament subunits. This neurofilament change is due to either direct mechanical failure of the axonal cytoskeleton or the initiation of a biochemical event that causes neurofilament disassembly. In general, the temporal progression of the intra-axonal changes that lead to ultimate disconnection is influenced by the severity of the traumatic injury and the species evaluated.

Animals↗

PubMed1998

Use of explant cultures of peripheral nerves of adult vertebrates to study axonal regeneration in vitro.

Explanted preparations of peripheral nerves with attached dorsal root ganglia of adult mammals and amphibia survive for several days in serum-free medium and can be used to study axonal regeneration in vitro. This review outlines the methods which we routinely use and how they may be applied to study different aspects of axonal regeneration. When the peripheral nerves are crushed in vitro, axons regenerate through the crush site into the distal stump within 1 day (mouse) or 3 days (frog). The outgrowth distance of the leading sensory axons can be determined with the use of a simple method based on axonal transport of labelled proteins. A compartmentalised system permits selective application of drugs and other agents to either ganglia or peripheral nerve containing the regenerating axons and has been used to study selected aspects of regeneration including influence of non-neuronal cells, retrograde signalling, axonal release of proteins during regeneration and the role of phospholipase A2 activity. Explanted preparations may also be cultured in a layer of extracellular matrix material (matrigel), in which spontaneous outgrowth of a large number of naked axons from the cut ends of nerves starts within 1 day and continues for several days. This provides an opportunity to study the direct effects of different agents on axonal elongation. Preparations cultured in collagen gels show sparse spontaneous axonal growth, but this can be increased by addition of certain growth factors. The phenotype of the regenerating axons can be studied using immunohistochemical methods.

Animals↗

PubMed2002

Cooling enhances in vitro survival and fusion-repair of severed axons taken from the peripheral and central nervous systems of rats.

Severed segments of rat peripheral (PNS; sciatic) and central nervous system (CNS; spinal) axons continue to conduct action potentials when maintained in vitro at 6-9 degrees C for up to 7 (sciatic axons) and 2 days (spinal axons), compared with only 36 h at 37-38 degrees C for sciatic axons and 6 h for spinal axons. These PNS and CNS axonal segments can be crushed and then treated with polyethylene glycol (PEG), resulting in a rapid reconnection (fusion) of the surviving axons at the crush site, as assessed by conduction of action potentials through the crush site within minutes after PEG administration. Severed PNS or CNS axons maintained in vitro at 6-9 degrees C prior to crushing can be successfully PEG-fused for up to 4 and 1.5 days, respectively, compared with only 24 (sciatic) and 3 h (spinal) at 37-38 degrees C. These data demonstrate that cooling significantly increases both the survival time of severed mammalian PNS and CNS axons and the time that severed axons can still be PEG-fused (rejoined) to rapidly re-establish axonal continuity in vitro.

Action Potentials↗

PubMed1999

Selective stabilization of microtubules within the proximal region of developing axonal neurites.

This study examined the distribution of labile and stable microtubules (MTs) during axonal neurite elaboration in NB2a/d1 cells using immunocytochemical markers of unmodified (tyrosinated; Tyr), modified (detyrosinated [Glu] and acetylated [Acet]) and total tubulin. Prominent total and Tyr tubulin immunoreactivity was relatively evenly distributed throughout axonal neurites. By contrast, Acet or Glu immunoreactivity was relatively concentrated within the proximal region of the neurite. Ultrastructural analyses demonstrated an array of longitudinal MTs that apparently span the entire neurite length. The observed differential localization of modified tubulin subunits in axonal neurites of these cells may therefore derive from selective stabilization of proximal regions of full-length axonal MTs. This was substantiated by the observation of Acet immunoreactivity on 30-50% of MTs within the most proximal axonal region, along with a proximal-distal decline to < or =5% of Acet immunoreactive MTs, in immunoelectron microscopy (immuno-EM) analyses. Microinjected biotinylated subunits were initially detected in assembled form within soma and proximal neurites, indicative of ongoing tubulin subunit incorporation into MTs within, and/or MT translocation into, proximal neurites. Because acetylation and detyrosination are functions of MT age, their concentration in this region despite deposition and/or transport of biotinylated tubulin suggests that a subset of axonal MTs undergoes subunit turnover and/or translocation at rates vastly slower than that of the majority of axonal MTs. Selective stabilization of the proximal region of a subset of axonal MTs may serve to construct a relatively stationary scaffold against which other axonal elements could translocate to more distal axonal regions for continued axonal outgrowth.

Acetylation↗

PubMed2000

Differentiated neurons retain the capacity to generate axons from dendrites.

Cutting the axon of a morphologically polarized neuron (stage 3) close to the cell body causes another neurite to grow as an axon [1-3]. Stage 3 neurons still lack molecular segregation of axonal and dendritic proteins, however. Axonal and dendritic compartments acquire their distinct composition at stage 4 (4-5days in culture), when proteins such as the microtubule-associated protein 2 (MAP-2) and the glutamate receptor subunit GluR1 localize to the dendrites and disappear from the axon [4,5]. We investigated whether cultured hippocampal neurons retained axon/dendrite plasticity after axons and dendrites have created their distinct cytoskeletal architecture and acquired their specific membrane composition. We found that axotomy of stage 4 neurons transformed a dendrite into an axon. Using axonal and dendritic markers, we tested whether cytoskeletal changes could cause similar transformations, and found that actin depolymerization induced multiple axons in unpolarized neurons. Moreover, depletion of actin filaments from both morphologically and molecularly polarized cells also resulted in the growth of multiple axons from pre-existing dendrites. These results imply that dendrites retain the potential to become axons even after molecular segregation has occurred and that the dendritic fate depends on the integrity of the actin cytoskeleton.

Animals↗

PubMed2000

The synthesis and transport of lipids for axonal growth and nerve regeneration.

Neurons are unique polarized cells in which the growing axon is often located up to a meter or more from the cell body. Consequently, the intracellular movement of membrane lipids and proteins between cell bodies and axons poses a special challenge. The mechanisms of lipid transport within neurons are, for the most part, unknown although lipid transport via vesicles and via cholesterol- and sphingolipid-rich 'rafts' are considered likely mechanisms. Very active anterograde and retrograde transport of lipid-containing vesicles occurs between the cell body and distal axons. However, it is becoming clear that the axon need not obtain all of its membrane constituents from the cell body. For example, the synthesis of phosphatidylcholine, the major membrane phospholipid, occurs in axons, and its synthesis at this location is required for axonal elongation. In contrast, cholesterol synthesis appears to occur only in cell bodies, and cholesterol is efficiently delivered from cell bodies to axons by anterograde transport. Cholesterol that is required for axonal growth can also be exogenously supplied from lipoproteins to axons of cultured neurons. Several studies have suggested a role for apolipoprotein E in lipid delivery for growth and regeneration of axons after a nerve injury. Alternatively, or in addition, apolipoprotein E has been proposed to be a ligand for receptors that mediate signal transduction cascades. Lipids are also transported from axons to myelin, although the importance of this process for myelination is not clear.

Animals↗

PubMed1990

Development of geniculocortical axon arbors in a primate.

The main objective of the present study was to describe the postnatal development of magnocellular and parvocellular LGN axons within the primate striate cortex. For this purpose, we bulk labeled axons in neonatal prosimians (galagos) in vivo or in vitro at regular intervals from birth (PO) to 12 weeks after birth by injecting horseradish peroxidase (HRP) into white matter anterior to the striate cortex. Filled axons within layer IV were reconstructed, quantitatively analyzed, and compared to a population of adult axons described previously (Florence & Casagrande, 1987). Our results show that although axons are morphologically immature at birth, they are restricted to the upper (IV alpha) and lower (IV beta) tiers of layer IV of the striate cortex as in adults. In adults, we referred to the presumed magnocellular LGN axons terminating in IV alpha as type I and the presumed parvocellular axons terminating in IV beta as type II. We used the same convention for developing axons. From birth to 3 weeks postnatal, type I and II axon classes are more variable in appearance than adult counterparts, and are not morphologically class distinct. As axons mature, parent axon shafts increase in caliber, arbors become smaller and more radial, and other immature features (e.g. spikes, protrusions, growth cones) are less evident. Both arbor classes mature slowly and some still exhibit immature features (e.g. growth cones) as late as 12 weeks postnatally. Although arbors do not show class-distinctive features until late in development, each class does show some unique maturational trends. Type I arbors are only slightly larger than adult counterparts at birth, whereas type II arbors are dramatically larger. Type I arbors increase in branch complexity with age, whereas type II arbors simply show a shift in complexity toward the center of the arbor with decreasing size over time. These growth trends suggest that magnocellular and parvocellular pathways to cortex could be differentially vulnerable to the manipulation of postnatal visual experience.

Animals↗

PubMed1990

Organization of individual cortical axons projecting from area V1 (area 17) to V2 (area 18) in the macaque monkey.

The present study uses the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), to investigate the detailed morphology of individual axons projecting from area V1 to prestriate area V2. Observations are derived from serial reconstructions of 45 axons. Axons are found to differ both in laminar distribution and in arbor size. The majority (25/45; 56%) terminate in the upper half of layer 4 and the lower part of layer 3. Terminal clusters typically measure about 200 microns in diameter (dimensions are uncorrected for shrinkage), and are either in one, two, or occasionally three patches. Patches are separated by 200-500 microns. Of these 25 axons, four also have minor collaterals to layer 5. Of the remaining 20 axons in our sample, eight have one or two terminal arbors (about 200 microns in diameter) mainly in layer 3; another eight have terminations, organized as a single field (about 350 microns in diameter), within layer 4; and four axons have much larger terminal fields (1.0-1.2 mm x 0.3 mm), in layers 3 and 4. These morphological differences might constitute a gradient or, alternately, indicate distinct subgroups within the striate efferent population. Large terminal fields are asymmetrical, with their long axis oriented in an anterior-posterior fashion toward the depth of the lunate sulcus. Axons with two terminal arbors have a similar bias. As this arrangement is approximately perpendicular to the border of V1, we suggest that striate axons may be extended preferentially along the length of the stripelike compartments in V2. These compartments are also arrayed perpendicular to the border between areas V1 and V2. Reconstruction of small groups of 2-4 convergent axons demonstrates that axons with different morphology (i.e. large or small terminal fields) can occur within the same projection focus. Terminal arbors belonging to different axons can overlap, but tend not to be superimposed exactly.

Animals↗