Longer Axons Research Articles

Four mutations of the spastin gene in Japanese families with spastic paraplegia

Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.

The RNA binding and transport proteins staufen and fragile X mental retardation protein are expressed by rat primary afferent neurons and localize to peripheral and central axons

Neuronal proteins have been traditionally viewed as being derived solely from the soma; however, accumulating evidence indicates that dendritic and axonal sites are capable of a more autonomous role in terms of new protein synthesis. Such extra-somal translation allows for more rapid, on-demand regulation of neuronal structure and function than would otherwise be possible. While mechanisms of dendritic RNA transport have been elucidated, it remains unclear how RNA is trafficked into the axon for this purpose. Primary afferent neurons of the dorsal root (DRG) and trigeminal (TG) ganglia have among the longest axons in the neuraxis and such axonal protein synthesis would be advantageous, given the greater time involved for protein trafficking to occur via axonal transport. Therefore, we hypothesized that these primary sensory neurons might express proteins involved in RNA transport. Rat DRG and TG neurons expressed staufen (stau) 1 and 2 (detected at the mRNA level) and stau2 and fragile x mental retardation protein (FMRP; detected at the protein level). Stau2 mRNA was also detected in human TG neurons. Stau2 and FMRP protein were localized to the sciatic nerve and dorsal roots by immunohistochemistry and to dorsal roots by Western blot. Stau2 and FMRP immunoreactivities colocalized with transient receptor potential channel type 1 immunoreactivity in sensory axons of the sciatic nerve and dorsal root, suggesting that these proteins are being transported into the peripheral and central terminals of nociceptive sensory axons. Based on these findings, we propose that stau2 and FMRP proteins are attractive candidates to subserve RNA transport in sensory neurons, linking somal transcriptional events to axonal translation.

SADly Promoting Neuronal Polarity

As neurons wire together networks of communication, they need to know not only which other neurons to connect to, but in which direction they should send signals. Such polarity within a single neuron is reflected by its morphology: Multiple short dendrites receive signals, and the single longer axon sends signals. Kishi et al. examined the role of SAD protein kinases, relatives of nematode synaptic differentiation regulators, in establishing neuronal polarity. Neurons lacking SADs did not polarize to produce morphologically and functionally distinct axons and dendrites. M. Kishi, Y. A. Pan, J. G. Crump, J. R. Sanes, Mammalian SAD kinases are required for neuronal polarization. Science 307 , 929-932 (2005). [Abstract] [Full Text]

A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses

The slow Wallerian degeneration phenotype, Wld(S), which delays Wallerian degeneration and axon pathology for several weeks, has so far been studied only in mice. A rat model would have several advantages. First, rats model some human disorders better than mice. Second, the larger body size of rats facilitates more complex surgical manipulations. Third, rats provide a greater yield of tissue for primary culture and biochemical investigations. We generated transgenic Wld(S) rats expressing the Ube4b/Nmnat1 chimeric gene in the central and peripheral nervous system. As in Wld(S) mice, their axons survive up to 3 weeks after transection and remain functional for at least 1 week. Protection of axotomized nerve terminals is stronger than in mice, particularly in one line, where 95-100% of neuromuscular junctions remained intact and functional after 5 days. Furthermore, the loss of synaptic phenotype with age was much less in rats than in mice. Thus, the slow Wallerian degeneration phenotype can be transferred to another mammalian species and synapses may be more effectively preserved after axotomy in species with longer axons.

Retinal target cells of the centrifugal projection from the isthmo-optic nucleus.

Although the avian retina has long been known to receive projection from a midbrain nucleus, the isthmo-optic nucleus (ION), the output of its target cells has remained obscure. We labeled the isthmo-optic (IO) terminals in the Japanese quail retina, by using anterograde transport of fluorescent tracer injected into the ION, and then labeled target cells for these terminals by means of intracellular tracer injection under direct microscopic observation. Somata of the IO target cells (IOTCs) lie in the innermost zone of the inner nuclear layer of the ventral half of the retina and have no dendrites but an axon. The axons run in the inner plexiform layer (IPL) for up to 6 mm and terminate densely in a round or elliptical terminal field, about 90-290 microm in diameter, of the outermost zone of the IPL. Longer axons (> 2 mm) extend dorsally, but shorter ones (< 1 mm) project ventrally or horizontally, so the terminals are distributed widely in both dorsal and ventral halves of the retina. The IOTCs cannot be classified into any of the five conventional major classes of retinal cells, including amacrine cells, and are thought to be "slave" neurons whose output is controlled by the neurons in the brain. Topographic separation between input to and output from the IOTCs by the axons might be essential for the overall topographic organization of the centrifugal visual system in birds.

The Usefulness of Sural/Radial Amplitude Ratio in the Diagnosis of Mild Axonal Polyneuropathy

Backgrounds and objectives： In the length-dependent axonal polyneuropathy, the distal part of the longer axons are affected earlier. In cases of mild axonal polyneuropathy, nerve conduction studies are frequently normal. We theorized that a sural/radial amplitude ratio (SRAR) might be a sensitive indicator of mild polyneuropathy. We investigated whether the SRAR may be a more sensitive indicator than sural amplitude alone in the diagnosis of mild axonal polyneuropathy.Methods： We analyzed medical records and electrophysiological studies of 32 patients with mild axonal polyneuropathy and 30 normal subjects. Sural amplitudes and SRAR in patients with signs of mild axonal polyneuropathy were compared to those of normal, age-matched control subjects. Sural and radial sensory amplitudes were measured in a standard method in all subjects.Results： Thirty five patients had an average SRAR of 0.26 as compared to 0.65 for the normal subjects. An SRAR of less than 0.50 was a strong predictor of axonal polyneuropathy, with the balance of sensitivity and specificity (80%), as compared to an absolute sural amplitude, which had sensitivity of only 57%. The SRAR did not vary significantly with age.Conclusion： We conclude that the SRAR is a useful electrodiagnostic test for mild axonal polyneuropathy.

Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury.

Immunoreactive substance P was investigated in turtle lumbar spinal cord after sciatic nerve transection. In control animals immunoreactive fibers were densest in synaptic field Ia, where the longest axons invaded synaptic field III. Positive neuronal bodies were identified in the lateral column of the dorsal horn and substance P immunoreactive varicosities were observed in the ventral horn, in close relationship with presumed motoneurons. Other varicosities appeared in the lateral and anterior funiculi. After axotomy, substance P immunoreactive fibers were reduced slightly on the side of the lesion, which was located in long fibers that invaded synaptic field III and in the varicosities of the lateral and anterior funiculus. The changes were observed at 7 days after axonal injury and persisted at 15, 30, 60 and 90 days after the lesion. These findings show that turtles should be considered as a model to study the role of substance P in peripheral axonal injury, since the distribution and temporal changes of substance P were similar to those found in mammals.

Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3.

In diabetic sensory polyneuropathy the earliest and most severe pathophysiology occurs in neurones with the longest axons. The aim of this study was to characterise a diabetes-induced neurodegenerative marker that was selective for sensory neurones with the longest axons. We studied alterations in calcium homeostasis since this occurs in other neurodegenerative diseases. Sensory neurones were cultured from control and streptozotocin-diabetic rats, treated with or without human recombinant neurotrophin-3 (hrNT-3), and neurones from L4-L6 dorsal root ganglia (DRG) which exhibit the longest axons in vivo were compared with those from C5-L3 DRG. Fluorescent video-imaging was used to measure cytoplasmic calcium dynamics. Streptozotocin diabetes of 8 to 14 weeks, induced an increase in resting internal Ca(2+) concentration ([Ca(2+)](i)), from 67 +/- 7 nmol/l in small neurones and 79 +/- 9 nmol/l in big neurones obtained from control animals to 214 +/- 19 nmol/l in small neurones and 273 +/- 30 nmol/l in big neurones after 14 weeks of diabetes ( p < 0.05) in L4-L6 DRG cultures. Neurones from C5-L3 ganglia and non-neuronal cells were not affected. Treatment of 14-week streptozotocin-diabetic rats with subcutaneous injection of 5 mg/kg NT-3 normalised the increase in resting [Ca(2+)](i). The amplitudes induced by depolarisation, caffeine and ATP [Ca(2+)](i) responses were reduced in small ( < 30 microm diameter) but not big ( > 35 microm diameter) neurones of L4-L6 DRG from streptozotocin-diabetic animals; the C5-L3 DRG were not similarly affected and the changes in the L4-L6 DRG were corrected by NT-3 treatment. Altered calcium homeostasis could be an early molecular marker linked to the onset of diabetic sensory neuropathy. This neurodegenerative index can be corrected by NT-3 therapy and should encourage further work aimed at understanding the mechanistic basis of these observations.

Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics

Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs, caused by the specific degeneration of the corticospinal tracts, the longest axons in humans. Most cases of the autosomal dominant form of the disease are due to mutations in the SPG4 gene, which encodes spastin, an ATPase belonging to the AAA family. The cellular pathways in which spastin operates and its role in causing degeneration of motor axons are currently unknown. By expressing wild-type or ATPase-defective spastin in several cell types, we now show that spastin interacts dynamically with microtubules. Spastin association with the microtubule cytoskeleton is mediated by the N-terminal region of the protein, and is regulated through the ATPase activity of the AAA domain. Expression of all the missense mutations into the AAA domain, which were previously identified in patients, leads to constitutive binding to microtubules in transfected cells and induces the disappearance of the aster and the formation of thick perinuclear bundles, suggesting a role of spastin in microtubule dynamics. Consistently, wild-type spastin promotes microtubule disassembly in transfected cells. These data suggest that spastin may be involved in microtubule dynamics similarly to the highly homologous microtubule-severing protein, katanin. Impairment of fine regulation of the microtubule cytoskeleton in long axons, due to spastin mutations, may underlie pathogenesis of HSP.

Soluble factors guide gonadotropin-releasing hormone axonal targeting to the median eminence.

Axons of GnRH neurons terminate at the median eminence in the medial basal hypothalamus (MBH) of the brain early in development. Similarly, GnRH neurons in grafts of preoptic area (POA) tissue within the third ventricle of hypogonadal mice preferentially innervate the median eminence. Organotypic cocultures of POA explants with other neural tissues suggest that a soluble substance(s) derived from the MBH may be directing this targeting. To begin to identify diffusable chemoattractants, we used preincubated heparin-coated acrylic beads to present specific solutes to POA explants on collagen- and laminin-coated membranes in insert chambers. GnRH axons grew on the membrane in greater number and with longer axons toward conditioned medium from MBH cultures than on the side away from the beads (P < 0.01). In contrast, GnRH axons showed no preferential outgrowth when incubated with beads soaked in control, defined medium. The attraction of MBH-conditioned medium was not generalizable to all neuroendocrine neurons, as it was not seen for galanin immunoreactive outgrowth from POA explants. There also were more GnRH axons toward conditioned medium from mouse brain microvascular endothelial cells, but no difference in axon length. Basic fibroblast growth factor (bFGF), a component of both endothelial cells and ventricular tanycytes, significantly attracted more and longer GnRH axons. Thus, bFGF may be one of the soluble factors directing GnRH outgrowth to the median eminence. However, as with so many other redundancies in the reproductive system, it is unlikely that it is the only targeting factor, as bFGF knockout mice are reported to be reproductively competent.

Quantitative and neurogenic analysis of neurons with supraspinal projections in the superficial dorsal horn of the rat lumbar spinal cord.

Dual retrograde axonal tracers, Fluoro-Gold (FG) and true blue (TB), were used in conjunction with [3H]thymidine autoradiography to determine the number and neurogenic pattern of neurons with supraspinal projections in the superficial dorsal horn (SDH), i.e., laminae I and II, in spinal segment L1 of the rat. FG was injected into rostral brain centers (dorsal thalamus and midbrain), and TB was injected into the caudal brainstem (medulla) in young adult rats previously administered [3H]thymidine in utero. Following stereological correction, each dorsal horn had an average of 1.22 neurons in lamina I and 0.24 neurons in lamina II that had supraspinal projections per 10-microm transverse section. In the SDH, 52% of the neurons with supraspinal projections were found to project to rostral brain centers alone, 3.0% only to the caudal brainstem, and 45% to both areas. There was no significant difference in the percentage distribution of each of the three groups of neurons between lamina I and lamina II. Cell counts in the present study, in conjunction with previous observations in the literature, suggest that the majority of supraspinal projection neurons in the SDH fall into two groups: 1) spinomesencephalic neurons with collaterals to the medulla and 2) spinothalamic neurons with collaterals to the midbrain. The neurogenesis of supraspinal projection neurons in the SDH proceeded along an axon-length gradient, whereby neurons with the longest axons, those with projections to rostral brain centers, completed neurogenesis prior to neurons with shorter axons, those with projections only to the caudal brainstem. The generation of all SDH neurons with supraspinal projections was completed on embryonic day 14 (E14), 2 days prior to the completion of neurogenesis for SDH neurons with intraspinal projections.

The Effect of Acrylamide and Other Sulfhydryl Alkylators on the Ability of Dynein and Kinesin to Translocate Microtubules in Vitro

Chronic exposure to acrylamide leads to a dying-back axonopathy afflicting the longest axons of all tested mammalian and avian species. Prior to the onset of acrylamide-induced axonal degeneration, alterations in axonal fast transport have been consistently reported to be more severe for the retrograde than the anterograde direction. The putative retrograde motor protein, dynein, is compromised by exposure to the sulfhydryl-alkylating agent N-ethylmaleimide (NEM) at concentrations far below those required to inactivate kinesin, the putative anterograde motor protein. Since acrylamide is capable of alkylating protein sulfhydryl moieties, we tested whether a direct exposure of purified kinesin or dynein to acrylamide would result in an impairment of either enzyme's ability to translocate microtubules. Motor activity was assayed by sequentially adsorbing either kinesin or dynein to acid-washed coverslips, treating with an alkylating agent or control solution, adding microtubules and ATP, and finally imaging and quantifying the binding and gliding of microtubules using video-enhanced differential interference contrast (VE-DIC) microscopy. In comparison to controls, incubation of dynein with NEM, ethacrynic acid, or iodoacetic acid resulted in dose-dependent decreases in the amount and rate of microtubule gliding, but increases in irreversible high-affinity microtubule binding. In contrast, exposure of dynein to 1-100 mM solutions of acrylamide did not significantly alter either the binding or gliding of microtubules (a molar/hour exposure to acrylamide equivalent to 50 times that which causes retrograde transport deficits in vivo). Likewise, kinesin motility parameters were not significantly affected by acrylamide concentrations up to 100 mM while NEM solutions > 100 microM led to significant losses in the ability of kinesin to bind MT. These data indicate that acrylamide does not significantly interact with bound (adsorbed) kinesin or dynein, implying that the mechanism by which acrylamide interferes with fast axonal transport in vivo is by interaction with other factor(s) that govern the movement of vesicles.

Astroglia demonstrate regional differences in their ability to maintain primary dendritic outgrowth from mouse cortical neurons in vitro

To determine whether glia from different regions of the central nervous system (CNS) initiate or maintain primary dendritic growth, embryonic day 18 mouse cortical neurons were co-cultured with rat (postnatal day 4) astroglial cells derived from retina, spinal cord, mesencephalon, striatum, olfactory bulb, retina, and cortex. Axon and dendrite outgrowth from isolated neurons was quantified using morphological and immunohistochemical techniques at 18 h and 1, 3, and 5 days in vitro. Neurons initially extend the same number of neurites, regardless of the source of glial monolayer; however, glial cells differ in their ability to maintain primary dendrites. Homotypic cortical astrocytes maintain the greatest number of primary dendrites. Glia derived from the olfactory bulb and retina maintained intermediate numbers of dendrites, whereas only a small number of primary dendrites were maintained by glia derived from striatum, spinal cord, or mesencephalon. Longer axons were initially observed from neurons grown on glia that did not maintain dendrite number. Axonal length, however, was similar on the various monolayers after 5 days in vitro. Neurons that were grown in media conditioned by either mesencephalic or cortical glia for the first 24 h followed by culture media from glia of the alternate source for 4 days in vitro confirmed that glia maintained, rather than initiated, the outgrowth of the primary dendritic arbor. These results indicate that glial cells derived from various CNS regions differ in their ability to maintain the primary dendritic arbor from mouse cortical neurons in vitro.

Spinal neurogenesis and axon projection: a correlative study in the rat.

The purpose of the present study was to determine the relationship between the duration of a spinal neuron's neurogenic period and the length of its axon or level of projection. Spinal segment L1 was chosen for examination and neurons were divided into four projection groups: 1) supraspinal projection (SSp), 2) long ascending propriospinal (LAPr), 3) short ascending propriospinal (SAPr), and 4) descending propriospinal (DPr). To determine the duration of the neurogenic period for each group, 3H-thymidine was administered to fetal rats during the proliferative period for spinal neuroblasts on one of embryonic (E) days E13 through E16. Between 50 and 100 days after birth neurons in each group were labeled with the retrograde fluorescent tracer Fluoro-Gold. To demonstrate nerve cells with SSp projections, spinal cords were hemisected at spinal segment C3 in one group of animals and Fluoro-Gold was applied to the sectioned surface of the cord. Three additional sets of animals were used to label nerve cells with LAPr, SAPr, and DPr projections by injecting Fluoro-Gold into the gray matter at spinal segments C6, T12, and L5, respectively. Neurons labeled with both Fluoro-Gold and 3H-thymidine and neurons labeled with Fluoro-Gold alone in each animal in each group were counted and the data statistically analyzed. Results showed that within each spinal lamina neurons with different projections were generated, i.e., completed cell division, at significantly different rates. Neurons with the longest axons, those with SSP projections, were generated first. These were followed by those with LAPr projections, and finally those with SAPr and DPr projections. In most laminate there was no significant difference between the neurogenic periods of rostrally projecting short propriospinal (SAPr) neurons versus caudally projecting short propriospinal (DPr) neurons. It was concluded that the duration of the neurogenic period for a given group of neurons within each spinal lamina is inversely related to the distance between the nerve cell and its projection site regardless of the direction of its projection.

Molecular mechanisms of gamma-diketone neuropathy.

We know from human and animal exposure data that inhalation of high concentrations of n-hexane are required, for prolonged periods of time, before a peripheral neuropathy will develop, a product of the rates of production of its ultimate toxic metabolite and of the reactions which occur within the axon (Yamamura, 1969; Herskowitz, et al., 1971). In both human and animal species, the greater vulnerability of long over short axons is a manifestation of the greater number of molecular targets for reaction with the toxic metabolite in the longer axons and a reflection of the stability of those targets. Looking back on the 20 years that we have been aware of this neurotoxicant, it is clear that these conclusions, so important to our understanding of the molecular pathogenesis of n-hexane neuropathy, might have been drawn from the clinical observation of these patients, and, subsequently, of exposed laboratory animals.KeywordsMolecular PathogenesisProtein CrosslinkingCovalent CrosslinkingAxonal SwellingLysyl ResidueThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Neurogenetic patterns in the medial limbic cortex of the rat related to anatomical connections with the thalamus and striatum

[ 3H]Thymidine autoradiography was used to investigate neurogenesis in all areas of the limbic cortex in the medial wall of the hemisphere. The experimental animals were the offspring of pregnant females injected with [ 3H]thymidine on 2 consecutive days: Embryonic Day (E)13–E14, E14–E15, …E21–E22, respectively. On Postnatal Day (P)60, the proportion of neurons originating during 24-h periods were quantified at nine anteroposterior levels. Three types of neurogenetic gradients are found. (i) Deep cells are older than superficial cells: layer VI is generated mainly on E15–E16, layer V on E16–E18, and layers IV-II on E18–E20. (ii) There is a ventral/older to dorsal/younger gradient between the dorsal peduncular, infralimbic, and anterior cingulate areas rostral to the genu of the corpus callosum. A ventral/older to dorsal/younger gradient is also found between superficial cells (layers II–IV) in anterior cingulate (CG3/CG1), posterior cingulate (CG2/CG1), and retrosplenial areas (RSG/RSA). (iii) An anterior/older to posterior/younger gradient is found between areas throughout the medial limbic cortex. Some of these neurogenetic patterns correlate with anatomical interconnections between the supracallosal medial limbic cortex (posterior cingulate and retrosplenial areas) and the anteroventral/anteromedial thalamic nuclei: older thalamic cells have longer axons that terminate in cortical areas containing younger cells, while younger thalamic cells have shorter axons that terminate in cortical areas containing older cells. Projections from the medial limbic cortex to the striatum also correlate with neurogenetic gradients: older cortical source cells in the infralimbic area project to the older striatal cells in the enkephalin-rich patches, while younger cortical source cells in the cingulate areas project to younger striatal cells in the surrounding matrix.

Medullary locomotor strip and column in the cat

Responses of lateral medullary neurons to microstimulation of two points in the locomotor strip—rostral and caudal to the obex—were recorded intracellularly in mesencephalic decerebellated uncurarized cats. Excitatory and inhibitory postsynaptic potentials and orthodromic action potentials occurred up to 20 ms after a single stimulus. A number of cells responded to stimulation of a locomotor point by a repetitive discharge, and in some cells synaptic responses were evoked by contralateral stimulation. The responsive neurons were scattered among other cells in the lateral medullary tegmentum. At least one-third of neurons with synaptic responses to stimulation of the rostral locomotor point were antidromically invaded from the caudal one. The characteristic length of these descending axons was between 4 and 9 mm, although there were longer axons too. The lateral medullary cells which give synaptic responses to stimulation of the locomotor strip form the locomotor column located medial to the strip, and a portion of these cells send their axons to the strip. It is suggested that the activity is propagated polysynaptically along the column through axonal collaterals of its neurons. One can assume that when repetitive stimulation achieves a threshold for locomotion such a propagation occurs without decrement. As a result, spinal stepping generators are activated.

Ultrastructural studies of the dying-back process. I. Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication.

The spatio-temporal pattern of distal peripheral nerve, sensory and motor nerve terminal, degeneration in experimental acrylamide neuropathy has been examined. Tissue was sampled from limbs of cats throughout various stages of intoxication (e.g. 7–32 days of 10 mg/kg/day and up to 294 days of 3 mg/kg/day of acrylamide) and examined by light and electron microscopy. Nerve terminals of a few Pacinian corpuscles in hindfoot and forefoot toepads displayed the first abnormalities, before the onset of clinical signs; filopod axon processes were lost, axolemmas disappeared and axoplasm was phagocytosed by inner core cells. Degeneration of adjacent primary annulospiral endings of muscle spindles in hindfoot muscle began shortly after the first changes in Pacinian corpuscle axons. Later, juxtaposed secondary muscle spindle endings and motor nerve terminals, supplying nearby extrafusal muscle fibers, began to degenerate. These sensory and motor nerve terminals accumulated neurofilaments, became swollen and disappeared. Contemporaneous with the early degenerative changes in some nerve terminals, seattered preterminal nodes, and their paranodes, displayed focal axonal accumulations of neurofilaments, mitochondria and dense bodies. These organelle conglomerations were associated with focal axonal swelling and paranodal retraction of myelin. This axonal change appeared to spread along internodes and to lead to fiber degeneration with the formation of ovoids which were later replaced by bands of Büngner. Fiber degeneration proceeded proximally as intoxication progressed. Above the proximal limit of fiber breakdown, axons displayed progressively fewer abnormalities in the form of adaxonal Schwann cell ingrowths and swollen paranodal regions. The cardinal conclusions of this study of acrylamide neuropathy are: 1-some distal sensory nerve endings (Pacinian corpuscle and annulospiral terminals) in the hindfeet begin to degenerate before adjacent motor nerve terminals supplying extrafusal muscles, and 2− the distal tips of the largest and longest axons are not most vulnerable, although there is a propensity for long and large axons to die-back first. In view of these observations, the etiology of the dying-back process requires re-examination.

Axonal transport in the asymmetric optic axons of flatfish

Axonal transport of protein was studied in the asymmetric optic axons of adult flounders, Pseudopleuronectes americanus. In these animals, the right optic nerve averaged 36% longer than the left optic nerve. There was no significant difference between the two sides in optic tract length or retinal ganglion cell body size. 3H-Proline was injected into the eyes and the amount of labeled protein accumulating in the optic tectum at selected intervals was measured by liquid scintillation counting. The rate at which proteins traveled with the fast component was estimated at 20–24 mm/day in both long and short axons; labeled protein, therefore, arrived in the right tectum earlier than in the left tectum. No such difference in accumulation of labeled protein could be demonstrated in the two tecta at longer intervals, suggesting that the rate of slow transport is not identical in the long and short axons, but that the net rate is greater in the longer axons. A consistently greater amount of labeled protein reached the right tectum at the longer intervals, indicating a greater utilization of the newly synthesized protein by the longer axons. The rate of slow transport thus seems to be influenced by the length of axon, perhaps in response to a greater rate of utilization of transported material required by the longer anox.

A light microscope study of the cytology and organization of neurons in the simple mammalian nucleus lateralis: columns and swirls.

The lateral nucleus in the rat is investigated with several variants of the rapid Golgi method and in Nissl preparations. The neurons are divided into two classes according to their size and the disposition of their axons. The smaller neurons or interneurons have cross sectional areas less than 180 μm2, and short axons that ramify in the vicinity of the cell bodies. Small neurons have also been seen on rare occasions with longer axons that may leave the nucleus. The larger cells (areas greater than 180 μm2) have long axons that leave the nucleus and emit short, beaded, recurrent collaterals. In the rostral and caudal poles of the lateral nucleus, the large projection neurons as well as the small neurons are multipolar with swirled dendritic arborizations. Neurons in the dorsal rim and ventral third of the nucleus have similar dispositions of their dendrites. In the central columnar zone, the projection neurons have dendrites that are arranged in columns directed diagonally across the body of the nucleus in the 4 to 10 o'clock direction in the right lateral nucleus and the 8 to 2 o'clock direction in the left nucleus. A collection of small neurons is generally found in the medial hilus zone. In each part of the lateral nucleus, the neurons are arranged in characteristic ways.