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PubMed1990

Taxol-induced neuropathy after nerve crush: long-term effects on regenerating axons.

Previous studies have shown that newly derived axonal sprouts are sensitive to the effect of taxol. Taxol induced an accumulation of microtubules in axonal sprouts, which resulted in giant axonal bulbs with the subsequent excessive proliferation of distorted axonal twigs from the distal end of swollen axonal bulbs 3 weeks after the nerve crush. The present study was performed to evaluate the chronic effects of taxol upon regenerative axons and the morphological changes have now been followed up to 40 weeks post injection (PI). The results showed that 1 month PI, the giant axonal bulbs with the conglomerations of haphazardly arranged axonal twigs were numerous at the lesion site. Later on, the axonal twigs, filled with axoplasmic microtubules, elongated and showed more longitudinal orientation as they grew distally. After 8 weeks PI the axonal elongation progressed and the majority of the original small axonal twigs disappeared and several larger diameter axonal branches developed. Some of the axonal branches emerging from the giant axonal bulbs became myelinated and survived while others degenerated. Ultrastructurally, the number of microtubules remained high in the surviving axonal branches up to 3 months PI. The degenerating branches showed an unexpected loss of microtubules 2 months onwards with the subsequent accumulation of degenerative axoplasmic material. However, neurofilaments were numerous in the degenerating axonal branches even when degenerative axoplasmic material was present. The present results show that some of the taxol-induced axonal twigs develop into larger diameter axonal branches which persist for up to 10 months. The cytoskeletal differences in the surviving versus the degenerating axonal branches suggests local regulatory mechanisms for regulation of axonal cytoskeleton in axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1983

Morphology of the rat carotid sinus nerve. II. Number and size of axons.

Ten carotid sinus nerves from five rats were examined by electron microscopy at a level of 0.5 mm from the glossopharyngeal nerve (nerve IX). The sinus nerves were found to contain from 455 to 757 (mean 625) axons per nerve, of which an average of 86.3% were unmyelinated. The unmyelinated axons had a size distribution that fitted a Gaussian distribution with a mean diameter of 0.78 micron and a variance of 0.013 micron. Such axons ranged in size from 0.17 to 1.7 microns. The myelinated axons had a unimodal size distribution skewed to the right, with a median total fibre diameter of 2.49 microns. Although total diameter of myelinated fibres ranged from 1.5 to 5.3 microns, 96% of such fibres were smaller than 4 microns. Axon diameter of myelinated fibres averaged 64% of the total diameter, but this proportion tended to increase with the size of the axon. Some 68% of myelinated fibres had axons with a diameter within the range of sizes of unmyelinated axons. The number of axons varied along the length of the sinus nerve, but no consistent pattern of change was found among different rats. The two nerves examined at 0.1 and 0.5 mm from nerve IX had 8-10 more myelinated axons at the more distal level, and the number of unmyelinated axons increased by four in one nerve but decreased by 26 in the other nerve. In three nerves examined at 0.5 and 2.0 mm from nerve IX, the number of unmyelinated axons increased from proximal to distal by 11 (2%) to 220 (43%), whereas the number of myelinated axons increased by 20 (48%) in one nerve but decreased by 7-10 (13-21%) in the others. One day after nerve IX was cut distal to the petrosal ganglion, most myelinated axons in the sinus nerve were degenerating and only 109 unmyelinated axons were still present. By four days all but two myelinated axons were gone and the normal complement of unmyelinated axons was replaced by more than 1800 rounded profiles, most of which probably were pseudopodia of reactive Schwann cells. Transection of nerve IX central to the petrosal ganglion did not produce such ultrastructural changes in Schwann cells, nor did it reduce the number of axons in the sinus nerve to a degree sufficient to be detected by the counting procedure. Although these results indicate that most axons in the sinus nerve are sensory, some nonsensory axons undoubtedly are present too. The sensory and nonsensory axons in the nerve apparently are closely associated with one another and in some cases might be enveloped by the same Schwann cells.

Animals↗
PubMed1982

The axo-axonic interneuron in the cerebral cortex of the rat, cat and monkey.

The synaptic connections of a specific type of identified cortical interneuron, the axo-axonic cell, were studied using Golgi methods. In the light-microscope axo-axonic cells were demonstrated in certain layers of the primary and secondary visual cortex of rat, cat and monkey, in the motor cortex of cat and in the subiculum and pyriform cortex of rat. The dendrites originating from the oval soma were oriented radially in a lower and upper spray within a cylinder about 100-150 microns wide. Electron-microscopy of Golgi impregnated, gold-toned axo-axonic cells showed predominantly but not exclusively asymmetrical synaptic contacts on their dendrites and spines, few synaptic contacts on the perikarya some of which were asymmetrical, and no synaptic contacts on the axon initial segment. The axon usually arborized within the vicinity of the cell's own dendritic field in an area 100-200 microns in diameter. In the kitten motor cortex the axon of a neuron in layer III descended to layer VI, providing a columnar arborization. The axon formed specialized, 10-50 microns long terminal segments invariably oriented parallel with the axon initial segment of pyramidal cells. All 85 identified symmetrical-type synaptic contacts, deriving from 31 specialized terminal segments, were found exclusively on the axon initial segment of pyramidal neurons. Rare, lone boutons of axo-axonic cells also made synaptic contact only with axon initial segments, confirming the exclusive target specificity of these cells. In identified gold-toned boutons, flattened pleomorphic vesicles were present. Electron-microscopy showed that axons ending in specialized terminal segments may originate from myelinated fibres, indicating that Golgi impregnation has revealed only part of the axon. Counting of axon terminal segments, each of which was in contact with the axon initial segment of a pyramidal neuron, revealed 166 pyramidal neurons receiving input from a partially reconstructed axo-axonic cell in the motor cortex of the kitten, and 67 from another cell in the visual cortex of the cat. The convergence of five axo-axonic cells onto one pyramidal cell was demonstrated in the striate cortex of the cat by counting all synaptic contacts on three initial segments. Cells from a one-month-old kitten were compared with those of the adult. The axon of the developing neurons was more diverse, having many growth cones and filopodia which made no specialized membrane contacts. However, the developing specific terminal segments formed synapses only with axon initial segments. It is concluded that the presence of axo-axonic cells in all the species and cortical areas we have examined suggests their association with the structural design of pyramidal cells, wherever the latter occur, and with their participation in the information processing of pyramidal cells. Axo-axonic cells are uniquely endowed with the means of simultaneously influencing the action potential at the site of origin in groups of pyramidal cells...

Animals↗
PubMed1987

Morphology of physiologically identified retinogeniculate X- and Y-axons in the cat.

1. We studied the morphology of individual, physiologically identified retinogeniculate axons in normal adult cats. The axons were recorded in the lateral geniculate nucleus or in the subjacent optic tract, characterized as X or Y by physiological criteria, penetrated, and injected with horseradish peroxidase. With subsequent application of appropriate histochemistry, the enzyme provides a complete label of the terminal arbors and parent trunks for morphological analysis. We have recovered for such analysis 26 X- and 25 Y-axons; of these, 14 X- and 12 Y-axons were studied in detail. 2. Within the optic tract, the parent trunk of every X-axon is located closer to the lateral geniculate nucleus and thus further from the pial surface than that of every Y-axon. This probably reflects the earlier development of X- than of Y-axons. Furthermore, the parent axon trunks of the X-axons are noticeably thinner than are those of the Y-axons. Every retinogeniculate X- and Y-axon in our sample branches within the optic tract. One of these branches heads dorsally to innervate the lateral geniculate nucleus and one heads medially and rostrally toward the midbrain, although none of these labeled axons were traced to a terminal arbor beyond the lateral geniculate nucleus. For Y-axons, all branches are of comparable diameter, but for X-axons, the branch heading toward the lateral geniculate nucleus is always noticeably thicker than is the branch directed toward the midbrain. 3. Every retinogeniculate X- and Y-axon produces the greatest portion of its terminal arbor in lamina A (if from the contralateral retina) or A1 (if from the ipsilateral retina). These arbors typically extend across most of the lamina along a projection line. Not a single terminal bouton from any axon was found in the inappropriate lamina A or A1 (i.e., in lamina A for ipsilaterally projecting axons or in lamina A1 for contralaterally projecting ones). Occasionally, an X-axon also innervates the medial interlaminar nucleus, and even more rarely does an X-axon innervate the C-laminae. In contrast, nearly all Y-axons from the contralateral retina branch to innervate part of the C-laminae (probably lamina C), and most from either retina also innervate the medial interlaminar nucleus. Although these details imply considerable variation in the overall pattern of retinogeniculate innervation for both X- and Y-axons, we found no physiological properties to correlate with this variation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

Synthesis of beta-tubulin, actin, and other proteins in axons of sympathetic neurons in compartmented cultures.

The proteins needed for growth and maintenance of the axon are generally believed to be synthesized in the cell bodies and delivered to the axons by anterograde transport. However, recent reports suggest that some proteins can also be synthesized within axons. We used [35S]methionine metabolic labeling to investigate axonal protein synthesis in compartmented cultures of sympathetic neurons from newborn rats. Incubation of distal axons for 4 hr with [35S]methionine resulted in a highly specific pattern of labeled axonal proteins on SDS-PAGE, with 4 prominent bands in the 43-55 kDa range. The labeled proteins in axons were not synthesized in the cell bodies, because they were also produced by axons after the cell bodies had been removed. Two of the proteins were identified by immunoprecipitation as actin and beta-tubulin. Axons synthesized <1% of the actin and tubulin synthesized in the cell bodies and transported into the axons, and 75-85% inhibition of axonal protein synthesis by cycloheximide and puromycin failed to inhibit axonal elongation. Nonetheless, the specific production by axons of the major proteins of the axonal cytoskeleton suggests that axonal protein synthesis arises from specific mechanisms and likely has biological significance. One hypothetical scenario involves neurons with long axons in vivo in which losses from turnover during axonal transport may limit the availability of cell body synthesized proteins to the distal axons. In this case, a significant fraction of axonal proteins might be supplied by axonal synthesis, which could, therefore, play important roles in axonal maintenance, regeneration, and sprouting.

Actins↗
PubMed1988

Morphology of retinogeniculate X and Y axon arbors in cats raised with binocular lid suture.

1. We examined the terminal arbors of single, physiologically identified retinogeniculate X and Y axons in 13 adult cats raised from birth with binocular lid suture. We recorded in the optic tract from 146 retinogeniculate axons. We studied the response properties of each axon encountered and attempted to penetrate it for labeling with horseradish peroxidase. 2. We attempted to classify each retinogeniculate axon as X or Y on a standard battery of tests. We thus identified 46 X and 91 Y axons; 5 axons had unusual response properties, and 4 axons were lost before they could be adequately identified. The X and Y axons had response properties that were completely normal by our criteria. The 5 unusual axons exhibited linear spatial and temporal summation, which is a property of X cells, despite all of their other tested response properties being consistent with those of Y cells. 3. We achieved complete, dark labeling of 13 X and 13 Y axons that form the data base for all of our qualitative and quantitative morphological observations. All of these labeled axons had response properties entirely normal for their X or Y class. Nine of the labeled X axons arise from the contralateral retina and 4 from the ipsilateral retina, whereas the respective numbers for the Y axons are 8 and 5. 4. Each of the individual retinogeniculate X axons form terminal arbors that appeared essentially normal in terms of location within geniculate lamina A or A1, shape, volume, and number of terminal boutons. 5. In contrast, the retinogeniculate Y axons form clearly abnormal arbors with diminished projections, both in terms of bouton numbers and arbor volumes. For Y axons from the contralateral retina, a roughly normal arbor is formed in the C-laminae, despite greatly diminished or absent projections formed in lamina A, something never seen in normal cats. For Y axons from the ipsilateral retina, the projections to lamina A1 are also diminished, and the arbors there are all limited to the ventral half of the lamina, a pattern rarely seen for normal Y axons. 6. The selective reduction in retinogeniculate Y axon arbors in these binocularly lid-sutured cats is consistent with similar observations reported for monocularly lid-sutured and strabismic cats but is quite different from the apparently normal development of retinogeniculate axon arbors in cats raised in complete darkness.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

The structure of the terminal arborizations of physiologically identified retinal ganglion cell Y axons in the kitten.

Retinal ganglion cell (r.g.c.) axons (n = 17) in the optic tract of 4-5 week-old kittens and adult cats (n = 4, this study, n = 27 from other reports) were studied both physiologically and morphologically. Axons were initially classified during extracellular recording with a battery of physiological tests that included Fourier analysis of the response to a sinusoidally counterphased sine-wave grating. Y axons had a significant second harmonic response component (greater than twice the fundamental) present independent of the spatial phase position of the grating. These axons were then recorded from intracellularly and subsequently filled ionophoretically with horseradish peroxidase (HRP). The HRP filled the axons' terminal arborizations in the dorsal lateral geniculate nucleus (l.g.n.). The innervation pattern and and structure of the terminal arborizations of the kitten r.g.c. Y axons were compared to those of the adult. The kitten Y axons innervated the l.g.n. in a pattern similar to that of the adult (individual branches from a single axon always innervated lamina A or A1 and may also have innervated lamina C, the medial interlaminar nucleus (m.i.n.) and/or sent branches that coursed medial to the l.g.n.). Fourteen of seventeen of these Y axons in the kitten innervated either of the A-laminae heavily (greater than 200 terminal boutons per axon). The remaining three r.g.c. Y axons in the kitten had only small arborizations within lamina A (less than fifty terminal boutons per axon) but heavily innervated lamina C. The structure of the terminal boutons on the kitten r.g.c. Y axons was highly variable when compared to axons of adult cats. Some of the boutons were spherical or crenulated as in the adult. Many others had filopodia and growth cone-like terminals with fine extensions. This variable maturation of terminal boutons was seen both between axons and on individual axons. The number of boutons on the kitten r.g.c. Y axons in the A-laminae was significantly less than that of adult Y axons. The mean numbers of boutons per axon were 476 and 1553 in the kittens and adult cats, respectively (P less than 0.001, Mann-Whitney U test). The width of the terminal arborization of individual Y axons in the A-laminae of the kittens was considerably smaller than in adult cats (mean widths of the terminal arborizations are 192 and 293 micron in the kittens and adult cats, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Cytotypic differences in the protein composition of the axonally transported cytoskeleton in mammalian neurons.

Many of the structural and functional differences between axons are thought to reflect underlying differences in the biochemical composition and dynamic aspects of the axonal cytoskeleton and cytomatrix. In this study we investigated how the composition of the 2 slow components of axonal transport, SCa and SCb, which convey the cytoskeleton and cytomatrix, differs in axons that are structurally and functionally distinct. For this comparison we analyzed axons of retinal ganglion cells in the optic nerve (ON), axons of dorsal root ganglion (DRG) cells, and axons of ventral motor neurons (VMN) in adult rats. 35S-Methionine-labeled proteins transported with the peak of SCa and SCb were analyzed using high-resolution 2-dimensional polyacrylamide gels (2D-PAGE) and fluorography, and the amounts of major SCa and SCb proteins were quantified. The polypeptide composition of both SCa and SCb was found to be largely similar in DRG and VMN axons, but major qualitative as well as quantitative differences between these axons and ON axons were found. Notable among these were higher ratios of neurofilament protein to tubulin in SCa in DRG and VMN axons compared to ON axons, and significantly larger amounts of 2 microtubule-associated proteins relative to tubulin in SCa of ON axons than in both VMN and DRG axons. Tubulin was the major SCb protein in VMN and DRG axons, but it was not present in SCb in ON axons. Additionally, relatively larger amounts of 2 metabolic enzymes, creatine phosphokinase and nerve-specific enolase, were present in SCb in ON axons than in DRG or VMN axons. The results indicate that significant biochemical heterogeneity among different types of axons can be identified by examining the slow components of axonal transport.

Actins↗
PubMed1991

Dual serotoninergic projections to forebrain in the rat: morphologically distinct 5-HT axon terminals exhibit differential vulnerability to neurotoxic amphetamine derivatives.

The cerebral cortex of the rat and other mammals is innervated by two morphologically distinct classes of serotoninergic (5-HT) axon terminals: fine axons with minute varicosities and beaded axons characterized by large, spherical varicosities. Fine and beaded 5-HT axons exhibit different regional and laminar distributions in forebrain and arise from separate brainstem nuclei, the dorsal and median raphe nuclei, respectively. The present neuroanatomic study, based on immunocytochemical methods to visualize 5-HT axons, demonstrates that the two axon types differ markedly in their vulnerability to the neurotoxic amphetamine derivatives, methylenedioxyamphetamine (MDA), and p-chloroamphetamine (PCA). While both drugs cause extensive degeneration of fine 5-HT axons throughout forebrain, beaded 5-HT axons are consistently spared. Fine 5-HT axons, which richly innervate most regions of dorsal forebrain in control rats, are rarely seen 2 weeks after treatment with MDA or PCA; this loss of fine axons reflects a marked denervation that persists for months after drug administration. The serotoninergic axon terminals remaining after MDA or PCA administration are almost entirely of the beaded type and appear to be unaffected by both drugs. Over a wide range of doses (2.5-40 mg/kg PCA) and survival times (2 weeks to 2 months), these spared 5-HT axons with large, spherical varicosities cannot be distinguished from the normal, beaded 5-HT axons in control rats by morphologic criteria. Moreover, beaded 5-HT axons exhibit a highly characteristic regional distribution which is the same in control as in MDA- and PCA-treated rats: these axons innervate specific zones or layers within parietal and occipital cortex, hippocampus, cingulate cortex, entorhinal cortex, and the olfactory bulb, among other forebrain areas, and they form a dense plexus lining the ventricular system. Taken together, the results of this study demonstrate that fine 5-HT axons are highly vulnerable to the neurotoxic effects of the amphetamine derivatives MDA and PCA, while beaded 5-HT axons are markedly resistant. These findings are consistent with the hypothesis that there are two anatomically and functionally distinct sets of serotoninergic neurons projecting to forebrain. While both of these neuronal systems utilize 5-HT as a neurotransmitter, they differ in several features: 1) origin from separate nuclei in the brainstem (the dorsal and median raphe), 2) two types of morphologically distinct axon terminals, 3) markedly different distribution and innervation patterns in forebrain, and 4) dissimilar pharmacological properties. The results further suggest that psychotropic amphetamine derivatives have a selective action upon fine serotoninergic axons that arise from the dorsal raphe nucleus.

3,4-Methylenedioxyamphetamine↗
PubMed1990

Macromolecular structure of axon membrane and action potential conduction in myelin deficient and myelin deficient heterozygote rat optic nerves.

The macromolecular structure of the axon membrane in optic nerves from 25-day-old male littermate control and myelin deficient (md) rats and 16-month-old md heterozygotic rats was examined with quantitative freeze-fracture electron microscopy. The axon membrane of control optic nerves displayed an asymmetrical partitioning of intramembranous particles (IMPs); P-fracture faces of myelinated internodal axon membrane were more particulate than those of pre-myelinated axons (approximately 1600 v 1100 microns-2, respectively), while relatively few IMPs (approximately 150 microns-2) were present on external faces (E-faces) of internodal or pre-myelinated axon membrane. Amyelinated axons of md optic nerves also exhibited an asymmetrical partitioning of IMPs; protoplasmic membrane face (P-face) IMP densities, taken as a group, exhibited a wide range (approximately 600-2300 microns-2) and, in most regions, E-faces displayed a relatively low IMP density (approximately 175 microns-2). Axons of greater than 0.4 microns diameter exhibited significantly greater mean P-face IMP density than axons less than 0.4 microns diameter. Aggregations of E-face IMPs (approximately 350 microns-2) were occasionally observed along amyelinated axon membrane from md optic nerves. Optic nerves from md heterozygote rats exhibit myelin mosaicism, permitting examination of myelinated and amyelinated axon membrane along the same tract. The axon membrane exhibits different ultrastructure in these two domains. Myelinated internodal axon membrane from md heterozygote optic nerves exhibits similar P- and E-face IMP densities to those of control internodal axolemma (approximately 1800 and 140 microns-2, respectively). Amyelinated axons in the heterozygote exhibit a membrane structure similar to amyelinated axons in md optic nerve. P-face IMP density of large diameter (greater than 0.4 microns) amyelinated axons from md heterozygote optic nerves is significantly greater than that of small calibre (less than 0.4 microns) axons. In most regions, amyelinated axon membrane exhibits a relatively low E-face IMP density (approximately 200 microns-2); however, focal aggregations (approximately 400 microns-2) of E-face particles are present. Electrophysiological recordings demonstrate that amyelinated axons in md optic nerves support the conduction of action potentials. Compound action potentials in md optic nerves exhibit a monophasic configuration, even at 20-days postnatal, similar to that of pre-myelinated optic nerve of 7-day-old normal rats. Moreover, conduction velocities in the amyelinated 20-day-old md optic nerve are similar to those displayed by pre-myelinated axons from 7-day-old optic nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMedDate not supplied

Transient axonal branching in the developing corpus callosum.

During development, there is a transient overproduction of axons in the corpus callosum; this overproduction of axons is due, in part, to a transient excess of neurons that send an axon through the corpus callosum. However, transient axonal branching could also contribute to the developmental overproduction of callosal axons. To investigate this possibility, we filled developing callosal axons in the Syrian hamster with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Light microscopic analysis showed that, indeed, developing callosal axons branch transiently in the hamster: branching was robust on postnatal day 0 (P0) and P3 (P0 = the first 24 hr after birth), less prominent on P6 and P8, and absent by P11. Immature callosal axons branched before or after crossing the midline and at all rostral-caudal and medial-lateral levels within the corpus callosum. The majority of callosal axon collaterals that were contained within individual 100-micron-thick sections were relatively short (mean = 15.1 microns) but some collaterals extended up to approximately 135 microns from the main axon trunk before passing out of the section in which they were observed. Nearly all of the collaterals emanated from the main axon trunk; higher-order collaterals were rare. Some callosal axon trunks had multiple collaterals. Branching callosal axons originated from multiple cortical areas, including area 17. Electron microscopic observations indicated that the processes designated as axon collaterals by light microscopic criteria would have been included in electron microscopic counts of developing callosal axons. Some callosal axon trunks and branches had ultrastructural features that suggested they were degenerating. In cats, developing callosal axons branch on embryonic day 57 (E57; the first 24 hr after conception = E0) and P0. Thus, it is likely that transient branching of immature callosal axons is a generalized feature of mammalian cortical development and that it contributes to the overproduction of callosal axons, albeit perhaps to varying degrees, in multiple species.

Aging↗
PubMed1985

Physiological properties of individual cerebral axons studied in vivo for as long as one year.

The long-term stability of conduction velocity and recovery processes were studied in a fast-conducting (corticotectal) and in a more slowly conducting (visual callosal) axonal system. Chronic microelectrode recording methods were used in conjunction with antidromic activation via electrical stimulation at one or more axonal site. These methods enabled 54 axons to be studied for greater than 20 days and seven of these cells to be studied for 101-448 days. The conduction velocities of corticotectal axons were characteristic of myelinated axons and were very stable over time. The conduction velocities of most callosal axons were characteristic of nonmyelinated axons, and 68% of callosal axons had conduction velocities that were stable over long periods of time. Of the remaining callosal axons, approximately one third showed an increase in conduction velocity (8-14%), whereas two thirds showed a progressive and systematic decrease in conduction velocity (6-81%). These changes in conduction velocity were distributed along the callosal axon, rather than limited to a single segment of axon. Although the refractory period of callosal and corticotectal axons showed considerable variability over time, the minimal interval between two conducted impulses was stable. The stability of this property was remarkable because the minimal interspike intervals of different axons with similar conduction velocities often differed greatly. Callosal axons show a supernormal period of increased conduction velocity following the relative refractory period and a subsequent subnormal period of decreased conduction velocity following a burst of prior impulses. In different callosal axons the magnitude of the velocity changes (percent change) differs greatly, even among axons of the same conduction velocity. For a given axon, however, these properties are very stable over time. These results on axonal properties may be useful in studies requiring the examination of extracellular responses of individual neurons over long periods of time. Antidromic latency provides a useful means of identifying a cell, particularly when conduction times are long. The stability of the minimal interspike interval and the supernormal period within individual axons make them suitable as ancillary criteria in identifying individual neurons. These three measures are independent of spike amplitude and waveform, and together they provide a "signature" by which individual cortical neurons can be identified over periods that represent a significant portion of the lifespan of adult mammals.

Animals↗
PubMed1992

Growth and targeting of subplate axons and establishment of major cortical pathways.

In the developing mammalian neocortex, the first postmitotic neurons form the "preplate" superficial to the neuroepithelium. The preplate is later split into a marginal zone (layer 1) and subplate by cortical plate neurons that form layers 2-6. Cortical efferent axons from layers 5 and 6 and cortical afferent axons from thalamus pass between cortex and subcortical structures through the internal capsule. Here, we identify in rats the axonal populations that establish the internal capsule, and characterize the potential role of subplate axons in the development of cortical efferent and afferent projections. The early growth of cortical efferent and afferent axons was studied using 1-1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) as an anterograde and retrograde tracer in aldehyde-fixed brains of embryonic rats. Cortical axons first enter the nascent internal capsule on embryonic day (E) 14 and originate from lateral and anterior cortex; axons from posterior cortex extend rostrally but do not yet exit cortex. The labeled axons, tipped by growth cones with complex morphologies, take a pathway deep to the preplate. Preplate neurons extend these early cortical efferents, based on the developmental stage of the cortex, and on their location and morphology. Most of these cells later occupy the subplate. Cortical plate neurons extend axons into the internal capsule by E16. En route to the internal capsule, cortical plate axons take the same path as the earlier-growing preplate axons, through the intermediate zone deep to subplate. Subplate axons reach thalamus by E16; the first cortical plate axons enter thalamus about a day later. Thalamic axons enter cortex by E16, prior to other cortical afferents. On E15, both preplate and thalamic axons reach the midpoint of the internal capsule. To determine the subcortical distribution of subplate axons, we used Dil as a retrograde tracer in aldehyde-fixed brains and fast blue and rhodamine-B-isothiocyanate as in vivo retrograde markers in neonatal rats. Tracers were injected into the superior colliculus, the principal midbrain target of layer 5 neurons, at times before, during, and after the arrival of cortical axons, or into the subcortical pathway of primary layer 5 axons at two points, the cerebral peduncle caudal to the internal capsule, and the pyramidal decussation at the junction of the hindbrain and spinal cord, at times shortly after the passing of cortical axons. In every case, the labeled neurons are confined to layer 5; subplate neurons are not labeled.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1975

Cinematographic analysis of contractile events produced in intrafusal muscle fibres by stimulation of static and dynamic fusimotor axons.

1. Muscle spindles with an intact blood supply and uninterrupted connexions with ventral and dorsal spinal roots (Bessou & Pagés, 1967, 1972) have been prepared in cat's tenuissimus muscles with the aim of cinephotographically recording intrafusal movements induced by the stimulation of single static or dynamic gamma axons; the time cours of these movements and the morphological kind of activated intrafusal muscle fibres have been established. 2. Displacements of spindle guiding marks in the equatorial region elicited by stimulating single static gamma axons are 4-20 times greater in amplitude than the ones elicited by stimulating dynamic gamma axons at the same frequency. 3. The dynamic gamma axons induced a contraction only in nuclear bag fibres which, in addition, never received any static gamma innervation. The static gamma axons evoked contractions either in nuclear bag fibres alone, or in nuclear chain fibres alone, or in both types of intrafusal fibres. Two thirds of static gamma axons supplied nuclear bag fibres. For various reasons, one half only of static gamma axons innervating nuclear bag fibres could be shown to simultaneously innervate nuclear chain fibres. Consequently, about one third of static gamma axons supplied both nuclear bag fibres and nuclear chain fibres, but it is highly probable that this latter figure is an underestimate. One third of static gamma axons produced contraction in nuclear chain fibres only. In this work, the distribution of fusimotor axons has been established in only one muscle spindle of the cluster of muscle spindles that each fusimotor axon is generally innervating. 4. Generally speaking, a static gamma axon elicits contraction of several intrafusal fibres whereas a dynamic gamma axon innervates only one intrafusal fibre and frequently only one pole of the fibre. 5. One third of static gamma axons evoked contractions in nuclear chain fibres that seemed to involve the whole pole. The other static gamma axons and all dynamic gamma axons produced, in the intrafusal fibres that they supplied, one or several foci of localized contractions. 6. The nuclear chain fibres contract and relax faster than nuclear bag fibres. The contractions of nuclear bag fibres supplied by static gamma axons are stronger and faster than those of nuclear bag fibres innervated by dynamic gamma axons. Nearly all nuclear bag fibres innervated by static gamma axons, like the nuclear chain fibres, show transient contractions at each pulse of a stimulation at low frequency (2-20/sec). 7. The results are discussed taking into account the available anatomical and physiological data on the muscle spindle. Their consequences with regard to intrafusal working are briefly considered.

Animals↗
PubMed1987

The distribution of axons according to diameter in the optic nerve and optic tract of the rat.

The distribution of axons according to diameter was examined in the optic nerve and optic tract of adult hooded rats. Observations were made on semithin sections, and measurements of axonal diameters were made on electron micrographs taken from various locations across thin sections through the optic nerve and tract. The distribution of axons by size differs markedly in the optic nerve and tract. Coarse (greater than 2 microns) and fine (less than or equal to 2 microns) axons are distributed throughout all regions of the optic nerve. In the optic tract, in contrast, coarse axons are especially dense dorsally, at the deep border of the tract, while they are absent ventrally, subjacent to the pial surface. No regions of the optic nerve contain densities of coarse axons as high as the deep nor as low as the superficial extremes of the optic tract. Nevertheless, even at the deep (dorsal) border of the optic tract, the coarse axons make up only a small minority (roughly 15%) of the total number of axons in that region. The axons 2 microns or smaller may be divisible into two overlapping, fine and intermediate, diameter classes, that are partially segregated within the optic tract, but not in the optic nerve: the distributions of axon diameters smaller than 2 microns are skewed to distinctly smaller diameters at the dorsal and ventral extremes of the optic tract, while in between, at mid-positions along the deep-to-superficial axis of the optic tract, the axon size distributions contain many more axons greater than 1 micron in diameter. These different axon diameter groups may arise from the morphologically distinct retinal ganglion cell types, and may underlie the components of the trimodal compound axon potential seen in the rat's primary optic pathway. Their partial segregation within the tract anticipates the partial segregation of their terminal arborizations within the laminae of the dorsal lateral geniculate nucleus. The rearrangement of axons into a partial segregation by size within the optic tract may indicate a chronology of axonal arrival during early development, proximity to the pial surface being an index of recency of arrival. As axonal outgrowth and neurogenesis appear to be directly related within the retinal ganglion cell population in mammals, the relative birthdates of the retinal ganglion cell types giving rise to the axon diameter classes in the rat may be inferred from the present results.

Animals↗
PubMed1988

Axon diameter distributions across the monkey's optic nerve.

The distribution of axons according to diameter has been examined in the optic nerve of old world monkeys. Axon diameters were measured from electron micrographs, and histograms were constructed at regular intervals across a section through the optic nerve to reveal the local axon diameter distribution. The total axon diameter distribution was also estimated. Fine-calibre optic axons (less than 2.0 micron in diameter) are found at all locations across the optic nerve. They are most frequent centrotemporally, where very few coarse optic axons can be found, but also make up the majority at the optic nerve's periphery. Coarse optic axons (greater than 2.0 microns in diameter) are increasingly common at progressively peripheral positions in the nerve. Around the nerve's circumference, these coarse optic axons are least numerous temporally, and most common dorsonasally. The axon diameter distribution peaks around 1.25 microns at most locations across the optic nerve, but there are more, slightly larger (1.5-2.0 microns), optic axons dorsally than ventrally. The estimated total axon diameter distribution is unimodal, peaking at 1.0-1.25 microns, with an extended tail towards larger diameters. This centroperipheral gradient of increasing axon diameters across the optic nerve is not substantial enough to account for the partial segregation of axons by size in the monkey's optic tract: there, coarse optic axons form a conspicuously greater proportion of the local axon diameter distribution along the tract's superficial (sub-pial) border, and fine optic axons are the only axons present near the tract's deep border. Hence, the fibre distribution in the optic tract cannot be formed by a simple combination of the fibre distributions of the two respective half-nerves, as described in the classic neuro-ophthalmologic literature. Rather, the present results, in conjunction with previous results from the optic tract, demonstrate that there must be a reorganization of axons by size in or near the optic chiasm.

Animals↗
PubMed1994

Microtubule transport and assembly cooperate to generate the microtubule array of growing axons.

MTs are major architectural elements in growing axons. MTs overlap with each other along the axon, forming an array that is continuous from the cell body to the tip of the axon. The MT array constitutes a scaffolding that mechanically supports the elongate shape of the axon and also contributes directly to its shape. MTs also direct the transport of vesicular organelles between the cell body and the axon, and thereby determine, in part, the composition of the axon. In this article, I have discussed mechanisms involved in the elaboration of the MT array in growing axons, and I have emphasized the distinct but complementary roles of polymer transport mechanisms and local assembly dynamics. MTs for the axon originate in the cell body, and they are delivered to the axon by the polymer transport mechanisms. These mechanisms thus contribute directly to the shape of the axon by supplying it with essential architectural elements. The shape of the axon is further modulated by dynamic processes that alter cytoskeletal structure locally along its length. These dynamic processes include the assembly/disassembly mechanisms which influence polymer length and possibly number locally along the axon by subunit exchange between the monomer and polymer pools. In addition, the polymer transport mechanisms themselves are subject to modulation along the axon, as demonstrated by the observation that transport rate of MTs varies along the length of individual axons (Reinsch et al., 1991). Such local variations can, in and of themselves, change the number of MTs along the axon, and thereby focally affect axon shape. Thus, the dynamic processes of polymer transport and local assembly act cooperatively to shape the MT array of the axon, and thereby contribute directly to the elaboration of axonal morphology.

Animals↗
PubMed1996

Differential nerve block. Direct measurements on individual myelinated and unmyelinated dorsal root axons.

BACKGROUND: Clinically, differential block is manifested by the loss of small fiber mediated sensation (e.g., temperature) two or more dermatomes beyond the sensory limit for large fiber mediated sensations. These observations support the belief that sensitivity to local anesthetics is inversely proportional to axon diameter. This study reports the first measurements of differential sensitivity to lidocaine in individual myelinated and unmyelinated mammalian dorsal root axons. METHODS: Lumbar dorsal roots and vagus nerves were isolated from anesthetized adult rats and maintained in vitro in a perfusion/recording chamber at 37 +/- 0.3 degrees C. Using single fiber techniques, evoked action potentials in individual myelinated and unmyelinated axons were digitized and recorded for subsequent analysis. Axons were exposed to lidocaine at 150, 260, or 520 microM. Sensitivity to local anesthetic was assessed by measuring the incidence of conduction block and the magnitude of conduction velocity slowing under steady-state conditions. RESULTS: Data were obtained from 77 dorsal root axons and 41 vagal axons. The estimated steady-state EC50 lidocaine concentration for myelinated dorsal root axons (232 microM) was comparable to that for unmyelinated axons (228 microM). Similarly, the incidence of conduction block was not significantly different among dorsal root axon groups. However, unmyelinated dorsal root axons were significantly less sensitive to the conduction velocity slowing effect of lidocaine than their myelinated counterparts (P < 0.01). The incidence of conduction block in short (mean length 13.5 mm) dorsal root axons was not significantly different from that in long (mean length 22.4 mm) axons. Compared with dorsal root axons, the estimated EC50s for vagal myelinated and unmyelinated axons (345 and 285 microM, respectively), while lower were not significantly different. However, the incidence of conduction block at 260 microM lidocaine was significantly lower (16.7% vs. 56.7%; P < 0.05) in vagal myelinated axons. CONCLUSIONS: Although no difference in sensitivity to the conduction blocking effects of lidocaine could be demonstrated among dorsal root axons, myelinated axons were more sensitive to the conduction velocity slowing effects of lidocaine. This differential effect cannot explain clinical observations of differential nerve block. Differential sensory block with lidocaine may depend on factors (e.g., physiologic function) related only indirectly to individual axon conduction velocity (diameter).

Anesthetics, Local↗