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PubMed1992

Axonal injury in closed head injury by assault: a quantitative study.

Due to the controversy in the literature regarding the time course of axonal balloon formation in human material, we wished to determine if it was possible to diagnose axonal injury before the development of axonal balloonings. The hypothesis was that the presence of axonal swellings or axonal enlargements associated with a glial reaction could be used as a diagnostic aid in human axonal injury before 12 hours. The brains of eight individuals that survived for less than 48 hours following head injury, and also had evidence of axonal injury using the criteria of Vanezis et al. (1987), were systematically studied by looking at axonal swellings, axonal balloonings, reactive astrocytes, maximum diameter of axonal enlargements and density of axonal enlargements. Controls were eight selected cases without neurological disease. The variables studied were assessed in 25 fields from ten different areas of the brain, using silver stains and immunoperoxidase for glial fibrillary acidic protein (GFAP). Logarithms of one plus the count of each variable were taken from the raw data and these were analysed using percentile distribution and the median, the t-test, Mann-Whitney U test and the Wilcoxon signed rank test. We conclude that quantitation of axonal damage allows the detection of mild degrees of axonal injury that could be overlooked on routine examination, and that the criteria of axonal enlargements, rather than axonal balloonings, are indications of axonal damage, cannot be endorsed with the evidence provided.

Axons↗
PubMed2005

Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons.

Recent studies have begun to focus on the signals that regulate axonal protein synthesis and the functional significance of localized protein synthesis. However, identification of proteins that are synthesized in mammalian axons has been mainly based on predictions. Here, we used axons purified from cultures of injury-conditioned adult dorsal root ganglion (DRG) neurons and proteomics methodology to identify axonally synthesized proteins. Reverse transcription (RT)-PCR from axonal preparations was used to confirm that the mRNA for each identified protein extended into the DRG axons. Proteins and the encoding mRNAs for the cytoskeletal proteins beta-actin, peripherin, vimentin, gamma-tropomyosin 3, and cofilin 1 were present in the axonal preparations. In addition to the cytoskeletal elements, several heat shock proteins (HSP27, HSP60, HSP70, grp75, alphaB crystallin), resident endoplasmic reticulum (ER) proteins (calreticulin, grp78/BiP, ERp29), proteins associated with neurodegenerative diseases (ubiquitin C-terminal hydrolase L1, rat ortholog of human DJ-1/Park7, gamma-synuclein, superoxide dismutase 1), anti-oxidant proteins (peroxiredoxins 1 and 6), and metabolic proteins (e.g., phosphoglycerate kinase 1 (PGK 1), alpha enolase, aldolase C/Zebrin II) were included among the axonally synthesized proteins. Detection of the mRNAs encoding each of the axonally synthesized proteins identified by mass spectrometry in the axonal compartment indicates that the DRG axons have the potential to synthesize a complex population of proteins. Local treatment of the DRG axons with NGF or BDNF increased levels of cytoskeletal mRNAs into the axonal compartment by twofold to fivefold but had no effect on levels of the other axonal mRNAs studied. Neurotrophins selectively increased transport of beta-actin, peripherin, and vimentin mRNAs from the cell body into the axons rather than changing transcription or mRNA survival in the axonal compartment.

Animals↗
PubMed2001

A role for cingulate pioneering axons in the development of the corpus callosum.

In many vertebrate and invertebrate systems, pioneering axons play a crucial role in establishing large axon tracts. Previous studies have addressed whether the first axons to cross the midline to from the corpus callosum arise from neurons in either the cingulate cortex (Koester and O'Leary [1994] J. Neurosci. 11:6608-6620) or the rostrolateral neocortex (Ozaki and Wahlsten [1998] J. Comp. Neurol. 400:197-206). However, these studies have not provided a consensus on which populations pioneer the corpus callosum. We have found that neurons within the cingulate cortex project axons that cross the midline and enter the contralateral hemisphere at E15.5. By using different carbocyanine dyes injected into either the cingulate cortex or the neocortex of the same brain, we found that cingulate axons crossed the midline before neocortical axons and projected into the contralateral cortex. Furthermore, the first neocortical axons to reach the midline crossed within the tract formed by these cingulate callosal axons, and appeared to fasciculate with them as they crossed the midline. These data indicate that axons from the cingulate cortex might pioneer a pathway for later arriving neocortical axons that form the corpus callosum. We also found that a small number of cingulate axons project to the septum as well as to the ipsilateral hippocampus via the fornix. In addition, we found that neurons in the cingulate cortex projected laterally to the rostrolateral neocortex at least 1 day before the neocortical axons reach the midline. Because the rostrolateral neocortex is the first neocortical region to develop, it sends the first neocortical axons to the midline to form the corpus callosum. We postulate that, together, both laterally and medially projecting cingulate axons may pioneer a path for the medially directed neocortical axons, thus helping to guide these axons toward and across the midline during the formation of the corpus callosum.

Age Factors↗
PubMed1986

Retinotectal projection in reeler mutant mice: relationships among axon trajectories, arborization patterns and cytoarchitecture.

The distribution of axons in the midbrain and thalamus of homozygous reeler mutant mice is anomalous. The cytoarchitecture of these regions is normal. In the normal mouse SC there is a distinct SO in which fascicles of retinotectal axons pass caudally before terminating in the overlying SGS. In reeler, by contrast, fascicles of retinotectal axons are distributed through the entire thickness of SGS as well as through SO. There are also abnormalities of fiber pattern in the thalamus, most notably in the region of the dorsal nucleus of the LGd. Retinotectal axon trajectory and patterns of terminal arborization in reeler and normal animals were compared by single-fiber HRP axonography. In normal mice, two distinct morphological classes of retinotectal axons form focal terminal arborizations at different radial levels in the superficial layers of the SC. Class U axons are of relatively small diameter and terminate in upper portions of SGS. Class L1 axons are of larger diameter and form terminal arbors which are confined to SO and deeper regions of SGS. Axons of both classes ascend to their terminal zones from parent axons which course through SO. Similarly, in reeler mice axons of both large and small diameter can be distinguished. However, many axons of both classes pass caudally in anomalous fascicles distributed through the full thickness of SGS and descend to terminate. Other axons pass in normal fashion in SO and ascend to terminate in SGS. Regardless of their trajectories, the small axons terminate superficially in SGS while the thick axons terminate deeper in SGS and/or SO, as in normal mice. These findings suggest that the ingrowth of afferents and the formation of terminal arbors are regulated by different mechanisms and that fiber architecture and cytoarchitecture are regulated by different mechanisms. It is not known if the anomalous fiber pattern in reeler adults arises in development through a defect in initial patterns of axon fasciculation or from a failure of axon elimination.

Animals↗
PubMed1987

6-Hydroxydopamine induces serotonergic axon sprouting in cerebral cortex of newborn rat.

Newborn rats were administered the neurotoxin 6-hydroxydopamine (6-OHDA) to determine whether neonatal ablation of the noradrenergic (NE) innervation produces augmented growth (i.e., sprouting) of serotonergic (5-HT) raphe-cortical axons. Following NE denervation at birth, the density of 5-HT axons in motor cortex (AG1) was determined at 4 days postnatal. Using a computer microscope system, the positions of all 5-HT-positive axons were mapped in radial strips of cortex from treated and control rats. Cumulative axon length, expressed as a function of area inspected, was used as a parameter of innervation density. Following 6-hydroxydopamine, the cumulative length of 5-HT axons in motor cortex increases by 32% (P less than 0.05) while cortical serotonin levels measured by HPLC concomitantly increase by 29% (P less than 0.005). The combined increases in 5-HT axon density and in neurotransmitter levels indicate that NE denervation produces increased growth of the cortical 5-HT innervation by the 4th postnatal day. The amount of transmitter stored per unit length of 5-HT axons appears unchanged. In 6-OHDA-treated rats, 5-HT axons exhibit augmented growth in all layers of motor cortex. In the treated rats, the relative density of 5-HT axons in each cortical layer is roughly proportional to the normal innervation density. Accordingly, in motor cortex, the magnitude of 5-HT axon sprouting is greatest in layer VI, which normally receives a dense 5-HT innervation, and is less in layer V, which has a lower innervation density. Qualitative assessment of other cortical areas following 6-OHDA reveals that 5-HT axon density appears increased in cortical zones that normally receive a dense 5-HT innervation, while the density remains low in zones with sparse innervation. The absence of axonal sprouting is particularly striking in those zones which receive a dense NE innervation but are sparsely innervated by 5-HT axons. Thus, while 5-HT axons undergo sprouting, they do not appear to replace ablated NE terminals in areas with a sparse 5-HT innervation. Hence, normal laminar and regional specificity of 5-HT axons is preserved despite ablation of NE afferents. These data indicate that, while NE denervation may trigger serotonergic sprouting, competition between NE and 5-HT fibers for the same postsynaptic sites is not the main factor that regulates postnatal growth of these axonal projections. The present findings demonstrate that the early development of raphe-cortical projections is influenced by NE cortical innervation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Independent guidance of retinal axons in the developing visual system of Drosophila.

The development of the adult visual system of Drosophila requires the establishment of precise retinotopic connections between retinal photoreceptor cell axons and their synaptic partners in the optic lobe of the brain. To assess the role of axon-axon interactions in retinal axon guidance, we used genetic methods to disrupt the normal spatiotemporal order of retinal axon ingrowth. We examined retinal axon projections to the developing first optic ganglion, the lamina, in two mutants in which reduced numbers of ommatidia develop in the eye imaginal disk. We find that in the developing lamina of these mutants, sine oculis and Ellipse, retinal axons project to proper dorsoventral positions despite the absence of the usual array of neighboring retinal axons. In a second approach, we examined animals that were somatic mosaics for the mutation, glass. In glass- animals, retinal axons project aberrantly and the larval optic nerve is absent. We find that in the developing lamina of glass mosaic animals, wild-type retinal axons project to proper dorsoventral positions despite the misrouted projections of neighboring glass- retinal axons. In addition, wild-type retinal axons project normally in the absence of the larval optic nerve, indicating that the latter is not an essential pioneer for retinal axon navigation. Our observations support the proposal that axon fascicles can make at least some pathfinding decisions independently of other retinal axon fascicles. We suggest that positional guidance cues that might label axon pathways and target destinations contribute to retinotopic pattern formation in the Drosophila visual system.

Animals↗
PubMed1989

Terminal arbors of single ON-center and OFF-center X and Y retinal ganglion cell axons within the ferret's lateral geniculate nucleus.

The lateral geniculate nucleus of the ferret contains not only eye-specific layers, but a further subdivision of layers A and A1 into inner and outer sublaminae that contain, respectively, ON-center and OFF-center cells (Stryker and Zahs, '83). To study how the arbors of single retinal ganglion cell axons correlate with these cellular divisions, we have examined the morphology of physiologically classified retinal axons in the ferret's lateral geniculate nucleus. As in cats, we could classify retinal axons as X or Y on the basis of a number of physiological criteria. X and Y axons have distinct patterns of termination in the lateral geniculate nucleus. Contralateral X axons innervate lamina A and ipsilateral axons lamina A1. X axons are further segregated in these laminae so that ON-center axons terminate in the inner sublamina, and OFF-center axons in the outer sublamina. We did not observe any branches of X axons innervating the medial interlaminar nucleus or the midbrain. Y axons have much larger terminal arbors and exhibit greater variation in their terminations. Generally, within layers A and A1, ON-center Y axons innervate the inner sublamina and OFF-center Y axons innervate the outer sublamina. However, they often innervate both sublaminae, and occasionally have a few boutons in the inappropriate lamina as well. Y axons also terminate in the dorsal C laminae, the interlaminar zones, and the media interlaminar nucleus; branches of these axons course toward the midbrain, presumably to innervate the superior colliculus. Thus, whereas the Y pathway in the ferret is one of high divergence, the X pathway appears to be the substrate for segregated ON and OFF channels through the lateral geniculate nucleus.

Animals↗
PubMed1987

The serotoninergic innervation of cerebral cortex: different classes of axon terminals arise from dorsal and median raphe nuclei.

The objective of the present study was to characterize the morphology of serotoninergic axons in cerebral cortex of the rat and to determine whether dissimilar axon terminals arise from the dorsal vs. the median raphe nuclei. The anterograde tracer PHA-L was administered by iontophoresis into the dorsal (DR) and median (MR) raphe nuclei, and the morphologic features of the respective axonal projections from raphe to forebrain were analyzed. We have observed consistent structural differences between the axons from these two nuclei. Anterogradely labeled axons which arise from cells in the MR are characterized by large, spherical varicosities (type M axons) and by variations in axonal diameter. In contrast, DR fibers are very fine and typically have small, pleomorphic varicosities that are granular or fusiform in shape (type D axons). Similar features of serotonin (5-HT) axon morphology are also evident in 5-HT immunocytochemical preparations. In addition to structural differences, there is a differential topographic distribution of MR vs. DR fibers, with MR axons concentrated in particular areas of limbic cortex such as dentate gyrus, posterior cingulate, and entorhinal areas as well as in parietal cortex. Immunofluorescence with dual labels shows that over two-thirds of the raphe-cortical axons are serotoninergic. The dissimilarities in axon morphology indicate that individual raphe nuclei may form different patterns of synaptic organization. Based on the evidence that the dorsal and median raphe nuclei give rise to morphologically different axon terminals, we conclude that 5-HT axons in cortex may be subdivided into two distinct projections. This proposal is in accord with other, recent data showing that the two axon types have different pharmacologic properties and are likely to be functionally different.

Afferent Pathways↗
PubMed1993

Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates.

The concept of shearing of axons at the time of non-impact injury to the head was first suggested in the middle of this century. However, no experimental model of diffuse axonal injury (DAI) has provided morphological confirmation of this concept. Evidence from experiments on invertebrate axons suggests that membrane resealing after axonal transection occurs between 5 and 30 min after injury. Thus, ultrastructural evidence in support of axonal shearing will probably only be obtained by examination of very short-term survival animal models. We have examined serial thin sections from the corpus callosum of non-human primates exposed to lateral acceleration of the head under conditions which induce DAI. Tearing or shearing of axons was obtained 20 and 35 min after injury, but not at 60 min. Axonal fragmentation occurred more frequently at the node/paranode but also in the internodal regions of axons. Fragmentation occurred most frequently in small axons. Axonal shearing was associated with dissolution of the cytoskeleton and the occurrence of individual, morphologically abnormal membranous organelles. There was no aggregation of membranous organelles at 20 and 35 min but small groups did occur in some axons at 60 minutes. We suggest that two different mechanisms of injury may be occurring in non-impact injury to the head. The first is shearing of axons and sealing of fragmented axonal membranes within 60 min. A second mechanism occurs in other fibres where perturbation of the axon results in axonal swelling and disconnection at a minimum of 2 h after injury.

Acceleration↗
PubMed1991

Weak-base amines inhibit the anterograde-to-retrograde conversion of axonally transported vesicles in nerve terminals.

Acidotropic weak-base amines were used to investigate the role of acidic compartments in the pathway of aterograde-to-retrograde conversion of axonally transported vesicles in axon terminals. A local concentrated population of nascent axon tips was produced by transecting the rat sciatic nerve in situ to allow local and direct exposure of the axon tips to test solutions. Immersion of the nascent axon tips in solutions containing 10 mM ammonium choloride or 10 mM propylamine caused the axon tips to become distended by an accumulation of elongated membranous tubules and occasional large vacuoles that were both distinct from retrograde organelles. To test whether this accumulation was the result of an impairment of anterograde-to-retrograde conversion, a radioactive pulse-labelling method was used together with a retrograde collection ligature, to quantify the proportion of anterogradely transported proteins that returned from the axon tips by retrograde transport. Exposure of the axon tips to 10 mM ammonium chloride caused the anterogradely transported membrane proteins to accumulate in the axon tips and reduced by about 50% the amount of protein that returned to the retrograde collection ligature. These observations implicate the involvement of acidic membranous compartments in the anterograde-to-retrograde conversion pathway that leads to the formation of retrograde organelles in axon tips. Exposure of nerves to Acridine Orange, which is a vital acidotropic fluorescent dye, confirmed the presence of acidic compartments in the axon tips. Based on these observations, we propose that the membranous tubules that accumulated in the axon tips in the presence of weak-base amines represent a transient intermediate in the pathway of anterograde-to-retrograde conversion of axonally transported vesicles in axon terminals, and that acidic membranous compartments within axon terminals are required for the conversion of these tubules into retrograde organelles.

Acridine Orange↗
PubMed1988

Projections and terminations of single respiratory axons in the cervical spinal cord of cat.

Position, divergence, branching, and termination patterns of single, respiratory axons were studied in cat cervical spinal cord by injecting horseradish peroxidase (HRP) intra-axonally. We stained 12 axons which were characterized by their firing patterns and by electrical stimulation. Five axons discharged during inspiration (I); the remaining 7 discharged during expiration (E). No injected axon was evoked by stimulating ipsilateral phrenic nerve roots while 7 (4 I, 3 E) of 12 were excited at a short latency from stimulating at a medullary site (on the midline, 1-2 mm rostral to the obex, approximately 3 mm below the dorsal medullary surface) where many bulbospinal respiratory axons decussate. All injected stem axons were located in the ventral and ventrolateral funiculi, traversed in a rostrocaudal direction, and were stained for lengths ranging from 3.6 to 12.4 mm. Mean axonal diameter was 2.9 microns. In 6 axons (4 I, 2 E), 14 collaterals were stained: 1 on each E axon, 2 on one I axon, 3 each on 2 others and 4 on another I axon. Collaterals emerged perpendicularly from the descending stem axon and projected directly to the ventral horn. The average distance between neighboring collaterals was 1.0 mm (n = 7). Collaterals did not arborize until they were near or within the ventral horn. Both en passant and terminaux types of presynaptic boutons were found primarily within the rostrocaudal cylinder that defined the phrenic motor column. In addition, some boutons were located dorsomedial to the phrenic motor column. We conclude that I axons, presumably of medullary origin, have multiple collaterals which terminate primarily in the phrenic motor column. However, the same axon can have terminals in different regions of the ventral horn, which are known to contain dendrites of phrenic motoneurons.

Animals↗
PubMed1986

Multiple fates of newly synthesized neurofilament proteins: evidence for a stationary neurofilament network distributed nonuniformly along axons of retinal ganglion cell neurons.

We have studied the fate of neurofilament proteins (NFPs) in mouse retinal ganglion cell (RGC) neurons from 1 to 180 d after synthesis and examined the proximal-to-distal distribution of the newly synthesized 70-, 140-, and 200-kD subunits along RGC axons relative to the distribution of neurofilaments. Improved methodology for intravitreal delivery of [3H]proline enabled us to quantitate changes in the accumulation and subsequent decline of radiolabeled NFP subunits at various postinjection intervals and, for the first time, to estimate the steady state levels of NFPs in different pools within axons. Two pools of newly synthesized triplet NFPs were distinguished based on their kinetics of disappearance from a 9-mm "axonal window" comprising the optic nerve and tract and their temporal-spatial distribution pattern along axons. The first pool disappeared exponentially between 17 and 45 d after injection with a half-life of 20 d. Its radiolabeled wavefront advanced along axons at 0.5-0.7 mm/d before reaching the distal end of the axonal window at 17 d, indicating that this loss represented the exit of neurofilament proteins composing the slowest phase of axoplasmic transport (SCa or group V) from axons. About 32% of the total pool of radiolabeled neurofilament proteins, however, remained in axons after 45 d and disappeared exponentially at a much slower rate (t 1/2 = 55 d). This second NFP pool assumed a nonuniform distribution along axons that was characterized proximally to distally by a 2.5-fold gradient of increasing radioactivity. This distribution pattern did not change between 45 and 180 d indicating that neurofilament proteins in the second pool constitute a relatively stationary structure in axons. Based on the relative radioactivities and residence time (or turnover) of each neurofilament pool in axons, we estimate that, in the steady state, more neurofilament proteins in mouse RGC axons may be stationary than are undergoing continuous slow axoplasmic transport. This conclusion was supported by biochemical analyses of total NFP content and by electron microscopic morphometric studies of neurofilament distribution along RGC axons. The 70-, 140-, and 200-kD subunits displayed a 2.5-fold proximal to distal gradient of increasing content along RGC axons. Neurofilaments were more numerous at distal axonal levels, paralleling the increased content of NFP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

Light-induced calcium influx into retinal axons is regulated by presynaptic nicotinic acetylcholine receptor activity in vivo.

Visual activity is thought to be a critical factor in controlling the development of central retinal projections. Neuronal activity increases cytosolic calcium, which was hypothesized to regulate process outgrowth in neurons. We performed an in vivo imaging study in the retinotectal system of albino Xenopus laevis tadpoles with the fluorescent calcium indicator calcium green 1 dextran (CaGD) to test the role of calcium in regulating axon arbor development. We find that visual stimulus to the retina increased CaGD fluorescence intensity in retinal ganglion cell (RGC) axon arbors within the optic tectum and that branch additions to retinotectal axon arbors correlated with a local rise in calcium in the parent branch. We find three types of responses to visual stimulus, which roughly correlate with the ON, OFF, and SUSTAINED response types of RGC reported by physiological criteria. Imaging in bandscan mode indicated that patterns of calcium transients were nonuniform throughout the axons. We tested whether the increase in calcium in the retinotectal axons required synaptic activity in the retina; intraocular application of tetrodotoxin (10 microM) or nifedipine (1 and 10 microM) blocked the stimulus-induced increase in RGC axonal fluorescence. A second series of pharmacological investigations was designed to determine the mechanism of the calcium elevation in the axon terminals within the optic tectum. Injection of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid-AM (BAPTA-AM) (20 mM) into the tectal ventricle reduced axonal calcium levels, supporting the idea that visual stimulation increases axonal calcium. Injection of BAPTA (20 mM) into the tectal ventricle to chelate extracellular calcium also attenuated the calcium response to visual stimulation, indicating that calcium enters the axon from the extracellular medium. Caffeine (10 mM) caused a large increase in axonal calcium, indicating that intracellular stores contribute to the calcium signal. Presynaptic nicotinic acetylcholine receptors (nAChRs) may play a role in axon arbor development and the formation of the topographic retinotectal projection. Injection of nicotine (10 microM) into the tectal ventricle significantly elevated RGC axonal calcium levels, whereas application of the nAChR antagonist alphaBTX (100 nM) reduced the stimulus-evoked rise in RGC calcium fluorescence. These data suggest that light stimulus to the retina increases calcium in the axon terminal arbors through a mechanism that includes influx through nAChRs and amplification by calcium-induced calcium release from intracellular calcium stores. Such a mechanism may contribute to developmental plasticity of the retinotectal system by influencing both axon arbor elaboration and the strength of synaptic transmission.

Animals↗
PubMed1999

Morphology of single pontine reticulospinal axons in the lumbar enlargement of the cat: a study using the anterograde tracer PHA-L.

The fine morphology of single pontine reticulospinal axons in the lumbar enlargement was investigated by using an anterograde Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing technique. Localized injections of PHA-L were made into the nuclei reticularis pontis oralis and caudalis in four cats. Following survival periods of 8-9 weeks, PHA-L-labeled axons were found throughout the lumbar enlargement from segments L4 to S2, in which the diameter of labeled axons was 0.6-2.5 microns. From serial transverse sections (50 microns), trajectories of 21 single pontine reticulospinal axons were traced in continuity over distances of 18.9-36.3 mm, corresponding to three to six segments, respectively. All the identified axons gave off multiple (two to nine) axon collaterals along their courses, with mean intercollateral distances of approximately 5-6 mm. Detailed reconstruction of the collateral arborization in the lumbar enlargement showed a high degree of similarity to that of single axons in the cervical enlargement previously reported (Matsuyama et al. [1997] J. Comp. Neurol. 377:234-250). First, axon collaterals arising from a majority (n = 18) of identified axons innervated the gray matter unilaterally, ipsilateral to the parent axons, whereas those from the remaining three axons innervated the gray matter bilaterally. Second, collateral projections terminated mainly in laminae VIII and VII, with the arborization field confined to a narrow rostrocaudal extent (< 1 mm). Third, the termination fields of axon collaterals arising from a given reticulospinal axon were similar at each segmental level and differed from one stem axon to another. These results suggest that the long descending pontine reticulospinal pathway is composed of different types of axons that may innervate the cervical and lumbar enlargements in continuity in a similar manner.

Animals↗
PubMed1996

Morphology of single axons of tectospinal neurons in the upper cervical spinal cord.

Morphology of single axons of tectospinal (TS) neurons was investigated by intraaxonal injection of horseradish peroxidase (HRP) at the upper cervical spinal cord of the cat. TS axons were electrophysiologically identified by their direct responses to stimulation of the contralateral superior colliculus (SC). None of these axons responded to thoracic stimulation at Th2. Three-dimensional reconstructions of the axonal trajectories were made from 20 well-stained TS axons at C1-C3. Cell bodies of these axons were located in the intermediate or deep layers of the caudal two-thirds of the SC. Usually, TS axons had multiple axon collaterals, and up to seven collaterals were given off per stem axon [2.7 +/- 1.6 (mean +/- S.D.); n = 20]. Collaterals had simple structures and ramified a few times mainly in the transverse plane. The number of terminals for each collateral was small. These collaterals terminated in the lateral parts of laminae V-IX, mainly in laminae VI, VII, and VIII. There were usually gaps free from terminal arborizations between adjacent collaterals, because the rostrocaudal spread of each collateral (mean = 700 microns) was narrower than the intercollateral interval (mean = 2,500 microns). Seven of the 19 TS axons had terminals in the lateral parts of laminae V-VIII, with little projection to lamina IX, and the other 12 axons had terminals in lamina IX besides the projection to the lateral parts of laminae V-VIII. Axon terminals in lamina IX did not appear to make contacts with the somata or proximal dendrites of retrogradely labeled motoneurons, but contacts were found with the somata of counterstained interneurons in the lateral parts of laminae V-VIII. Three spinal interneurons (two in lamina VIII and one in lamina V at C1) that received monosynaptic excitation from the SC were stained, and their axonal trajectories were reconstructed. They had multiple axon collaterals at C1-C2 and mainly projected to laminae VIII and IX, with smaller projections to lamina VII. Many axon terminals of the interneurons were found in multiple neck motor nuclei, where some of them made contacts with retrogradely labeled motoneurons. The present finding provides evidence that the direct TS projection to the spinal cord may influence activities of multiple neck muscles, mainly via spinal interneurons, and may play an important role in control of head movement in parallel with the tectoreticulospinal system.

Animals↗
PubMed2005

Acute inactivation of MAP1b in growing sympathetic neurons destabilizes axonal microtubules.

Microtubule-associated-protein 1b (MAP1b) is abundant in neurons actively extending axons. MAP1b is present on microtubules throughout growing axons, but is preferentially concentrated on microtubule polymer in the distal axon and growth cone. Although MAP1b has been implicated in axon growth and pathfinding, its specific functions are not well understood. Biochemical and transfection studies suggest that MAP1b has microtubule-stabilizing activity, but recent studies with neurons genetically deficient in MAP1b have not confirmed this. We have explored MAP1b functions in growing sympathetic neurons using an acute inactivation approach. Neurons without axons were injected with polyclonal MAP1b antibodies and then stimulated to extend axons. Injected cells were compared to controls in terms of axon growth behavior and several properties of axonal microtubules. The injected antibodies rapidly and quantitatively sequestered MAP1b in the cell body, making it unavailable to perform its normal functions. This immunodepletion of MAP1b had no statistically significant effect on axon growth, the amount of microtubule polymer in the axon, and the relative tyrosinated tubulin content of this polymer, and this was true in sympathetic neurons from rat, wild type mice, and tau knockout mice. Thus, robust axon growth can occur in the absence of MAP1b alone or both MAP1b and tau. However, immunodepletion of MAP1b significantly increased the sensitivity of microtubules in the distal axon and growth cone to nocodazole-induced depolymerization. These results indicate that MAP1b has microtubule-stabilizing activity in growing axons. This stabilizing activity may be required for some axonal functions, but it is not necessary for axon growth.

Animals↗
PubMed1986

A quantitative analysis of frog optic nerve regeneration: is retrograde ganglion cell death or collateral axonal loss related to selective reinnervation?

The present study was designed to assess whether axon collateral formation and loss or retrograde cell death contribute to selective reinnervation during optic nerve regeneration in the frog, Rana pipiens. The right optic nerve was crushed in 18 frogs, and samples were taken near the optic disc (retinal segment) and near the optic chiasm (brain segment). These samples were studied quantitatively with the electron microscope at various postoperative survival times (1, 2, 3, 4, 6, 12 weeks, 6 months, 1 year; N = 2). The number and size of axons in each segment were estimated from a series of electron micrographs taken at intervals across the transverse extent of each nerve and compared with normal nerves (N = 4). Results show that there are 5.3 +/- 1.8 X 10(5) (S.D.) unmyelinated and 2.3 +/- .5 X 10(4) myelinated axons in the normal nerve. One week post-crush (p.c.) there is a 27% decrease in the number of axons in the retinal segment (4.1 +/- 1.4 X 10(5)), indicating early retrograde axonal loss. As expected, there is a greater loss of axons at this time in the brain segment (3.0 +/- 1.3 X 10(5)). Between 2 and 6 weeks p.c. the number of axons increases in the retinal segment to over twice the normal number of axons increases in the retinal segment to over twice the normal number (12.3 +/- 3.8 X 10(5)) and to over four times this number in the brain segment (20.0 +/- 3.0 X 10(5)), showing collateral axon formation results from this injury. A large loss in the number of axons occurs in both nerve segments between 6 and 12 weeks p.c. (4.3 +/- 1.5 X 10(5)) and an additional loss at 20 weeks p.c. (2.2 +/- .98 X 10(5)). Subsequently, the number remains constant, approximately 40% of normal. Visual recovery was seen in the two frogs tested one year after optic nerve crush that were used for optic axon counts. Autoradiography in these same animals showed the optic nerve projections normally seen after regeneration. Besides axonal loss, our results also indicate that the size of both myelinated and unmyelinated axons is significantly above normal at chronic postoperative periods. This increase in axonal size is interpreted to be related to the increased territory each remaining optic axon must fill to restore the optic projections.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Age changes in axon number along the cervical ventral spinal nerve roots in rats.

Axon counts were made at two standardised levels of C7 ventral spinal nerve roots from 46 female rats representing nine ages between birth and 500 days. The objective was to provide a definitive account of proximodistal changes in axon numbers and of age changes in axon numbers both during postnatal development and at several stages during maturity. At each age there is a proximodistal increase in the numbers of axons in all categories examined (myelinated, promyelin, transitional, and fetal) between levels midway along the subarachnoid course of the root and where it is apposed to but separate from the dorsal root ganglion. During maturation and throughout maturity axon totals change similarly at both levels: After a slight increase immediately postnatum, they decline sharply between 4 and 20 days due to a marked loss of unmyelinated axons. A gradual decline in myelinated axon numbers continues to 500 days. While these changes are occurring, axon numbers in all categories show a proximodistal increase throughout. The magnitude of this increase lessens with age for all but the transitional category due to a preferential decrease in numbers distally. Though these observations do not differentiate between axon branching and looping of sensory axons into the ventral root as a cause of the proximodistal increase in numbers, they tend to support the former. At each age during maturation axon proportions at proximal and distal levels correspond well for each animal, indicating that axon segregation proceeds at related rates within each root. Age changes in axon proportions within the transitional and fetal categories indicate that the postnatal stage of axon segregation results from axon loss, rather than Schwann cell proliferation.

Aging↗