Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Axons”

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

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

At least 685 records · Page 38Linked to original sources
PubMed2006

Immobilized nerve growth factor and microtopography have distinct effects on polarization versus axon elongation in hippocampal cells in culture.

Cell interfacing with biomaterial surfaces dictates important aspects of cell behavior. In particular, axon extension in neurons is effectively influenced by surface properties, both for the initial formation of an axon as well as for the maintenance of axon growth. Here, we investigated how neurons behaved on poly(dimethyl siloxane) (PDMS) surfaces decorated with biochemical and physical cues presented individually or in combination. In particular, nerve growth factor (NGF) was covalently tethered to PDMS to create a bioactive surface, and microtopography was introduced to the material in the form of microchannels. Embryonic hippocampal neurons were used to investigate the impact of these surface cues on polarization (i.e., axon initiation or axogenesis) and overall axon length. We found that topography had a more pronounced effect on polarization (68% increase over controls) compared to immobilized NGF (0.1 ng/mm(2)) (27% increase). However, the effect of NGF was negligible when both types of stimuli were simultaneously presented on the biomaterial surface. In addition to axon formation, chemical and physical cues are also involved in axon growth following the initiation process. Interestingly, for the same studies described above, the effects of microchannels and NGF were opposite from the effects on polarization; the most evident effect was for the immobilized growth factor (10% increase in axon length with respect to controls) whereas there was no effect in general for the microtopography. More importantly, when the two surface stimuli were presented in combination, a synergistic increase in axon length was detected (25% increase with respect to controls), which could be a result of faster polarization triggered by topography plus enhanced growth from NGF. Additionally, axon orientation was also analyzed and we found the well-known tendency of perpendicular or parallel axonal alignment to be dependent on the width and depth of the channels. This investigation thoroughly compared and distinguished the individual and combined impact of material surface properties (chemical and physical) on axogenesis from the effects on axon length. Overall, topography dominated polarization mechanisms, whereas NGF, and particularly a synergy of immobilized NGF plus topography, dominated axon length. These results could be potentially applied for the design of biomaterials in applications were axon growth is critical.

Animals↗
PubMed2005

Mitochondrial dysfunction plays a key role in progressive axonal loss in Multiple Sclerosis.

Multiple Sclerosis is the most common inflammatory demyelinating disease of the central nervous system and is the leading cause of non traumatic neurological disability in young adults. In recent years it has become increasingly evident that axonal degeneration is a key player in the pathogenesis of disability in MS but the mechanisms that lead to axonal damage are not fully understood. It seems likely that the causes of axonal damage vary at different stages of the disease and several theories have evolved that address the mechanisms leading to axonal loss in the acute stages of demyelination. There has been relatively little attention given to investigation of the mechanisms involved in chronic axonal loss in the progressive stages of MS. We propose a hypothesis that mitochondria play a key role in this chronic axonal loss. Following demyelination there is redistribution of sodium channels along the axon and mitochondria are recruited to the demyelinated regions to meet the increased energy requirements necessary to maintain conduction. The mitochondria present within the chronically demyelinated axons will be functioning at full capacity. The axon may well be able to function for many years due to these adaptive mechanisms but we propose that eventually, despite antioxidant defences, free radical damage will accumulate and mitochondrial function will become compromised. ATP concentration within the axon will decrease and the effect on axonal function will be profound. The actual cause of cell death could be due to a number of mechanisms related to mitochondrial dysfunction including failure of ionic homeostasis, calcium influx, mitochondrial mediated cell death or impaired axonal transport. Whatever the cause of axonal loss our hypothesis is that mitochondria are central to this process. We explore steps to test this hypothesis and discuss the possible therapeutic approaches which target the mitochondrial mechanisms that may contribute to chronic axonal loss.

Adult↗
PubMed2005

Regenerating supernumerary axons are cholinergic and emerge from both autonomic and motor neurons in the rat spinal cord.

Multipolar neurons in the mammalian nervous system normally exhibit one axon and several dendrites. However, in response to an axonal injury, adult motoneurons may regenerate supernumerary axons. Supernumerary axons emerge from the cell body or dendritic trees in addition to the stem motor axon. It is not known whether these regenerating axons contain neurotransmitters for synaptic transmission at their terminals. Here, using immunohistochemistry for choline acetyltransferase, an enzyme that synthesizes acetylcholine, we demonstrate the emergence of cholinergic supernumerary axons at 6 weeks after a unilateral L5-S2 ventral root avulsion and acute implantation of the avulsed L6 ventral root into the adult rat spinal cord. Light microscopic serial reconstruction of choline acetyltransferase immunoreactive arbors shows that these supernumerary axons originate from both autonomic and motor neurons. The supernumerary axons emerge from the cell body or dendrites, exhibit an abnormal projection pattern within the intramedullary gray and white matters, make frequent abrupt turns in direction, and form bouton-like swellings as well as growth cone-like terminals. Double labeling immunohistochemistry studies show that the choline acetyltransferase immunoreactive supernumerary axons co-localized with two proteins associated with axonal growth and elongation, growth-associated protein 43 and p75, the low affinity neurotrophic factor receptor. Our findings suggest that regenerating supernumerary axons selectively transport and store choline acetyltransferase, supporting the notion that supernumerary axons may develop functional and active synaptic transmission. Therefore, regenerating supernumerary axons may contribute to the plasticity in neural circuits following injury in the adult nervous system.

Animals↗
PubMed1996

A re-examination of sex differences in axon density and number in the splenium of the rat corpus callosum.

Previous work from our laboratory reported a sex difference in axon number in the splenium of the adult rat corpus callosum. However, the cortical origin of the axons that were sampled is unknown and sex differences may exist in the topography of axons in this area. The present study revisits the issue of sex differences in axon number in the splenium. First, the topographical organization of axons in the splenium was investigated. Rats each received single intracortical injections of horseradish peroxidase (HRP). The location of HRP labelled fibers in the corpus callosum was compared across the various injection sites. There is a rostrocaudal organization of axons in the splenium based on rostral to caudal cortical location that does not vary by sex. Second, visual axons, which comprise the posterior fifth (relative to overall length) of the corpus callosum in both sexes, were thoroughly sampled with electron microscopy. Significant dorsoventral and rostrocaudal variation in myelinated and unmyelinated axon density was found. While axon density varied to some extent depending on the sex of the animal, axon number calculations revealed no sex differences in total axon number. Males, however, had significantly more myelinated axons than females. Thus, sex differences in axon density in the adult rat splenium were regional and did not result in overall sex differences in axon number.

Animals↗
PubMed1997

Ganglionic axons in motor roots and pia mater.

In addition to motor axons and preganglionic axons, ventral roots contain unmyelinated or thin myelinated sensory axons and postganglionic sympathetic axons. It has been said that ventral roots channel sensory axons to the CNS. However, it now seems that these axons end blindly, shift to the pia or loop and return towards the periphery and that these units reach the CNS via dorsal roots. Sensory ventral root axons project from a variety of somatic or visceral receptors; some of them are third branches of dorsal root afferents and some seem to lack a CNS projection. Many ventral root afferents contain substance P (SP) and/or calcitonin gene-related peptide (CGRP). These fibres are not affected by neonatal capsaicin treatment and they cannot induce radicular or pial extravasation. Some thin ventral root axons are sympathetic and relate to blood vessels. Afferents containing SP and/or CGRP and sympathetic axons also occur in the spinal pia mater. The sensory axons mediate pain. They might also have vasomotor, tissue-regulatory and/or mechanoreceptive functions. The motor roots of cranial nerves IV, VI and XI contain unmyelinated axons arranged like in ventral roots outside the autonomic outflow. However, the motor root of cranial nerve V channels some unmyelinated axons into the CNS. The occurrence of thin axons in ventral roots and pia mater changes during development and ageing. After peripheral nerve injury, ipsilateral ventral roots and pia are invaded by new sensory and postganglionic sympathetic axons.

Animals↗
PubMed2002

The non-immunosuppressive immunophilin ligand GPI-1046 potently stimulates regenerating axon growth from adult mouse dorsal root ganglia cultured in Matrigel.

We used explant cultures of adult mouse dorsal root ganglia with spinal nerve attached growing in Matrigel to assess the effects of the non-immunosuppressive immunophilin ligand GPI-1046 [Snyder et al. (1998) TIPS 19, 21-26] on the growth rate of regenerating sensory axons and found a potent stimulation of axon growth. In these explant cultures, naked, unfasciculated axons emerge from the cut end of the spinal nerve and continue to grow in the Matrigel for up to eight days [Tonge et al. (1996) Neuroscience 73, 541-551]. Some axons are entirely smooth whilst others show prominent varicosities. Some of the former express the phosphorylated neurofilament epitope recognised by monoclonal antibody RT97, a marker for large calibre, myelinated axons, whilst the latter express calcitonin gene-related peptide, predominantly a marker for unmyelinated, and small diameter myelinated sensory axons. Many of the axons in these cultures also express the low-affinity neurotrophin receptor p75. GPI-1046 has been shown to have striking stimulatory effects on embryonic primary sensory axons growing in vitro and it was therefore of interest to see whether it could also enhance regenerating sensory axon growth from the adult ganglia in our cultures. GPI-1046 potently stimulated axon growth in our cultures in a dose-dependent manner. The stimulatory effect was not dependent on the class of sensory axon. These observations show that GPI-1046 is a potent stimulator of regenerating axons from adult, primary sensory neurones. The cellular site of action of GPI-1046 is unknown. To distinguish between a direct effect of the drug on neurones and an indirect effect we compared the effects of GPI-1046 on explant and dissociated cultures. In confirmation of previous results, we found that GPI-1046 potently stimulated axon outgrowth from explants of embryonic chick dorsal root ganglia. However, the drug was without effect on dissociated embryonic dorsal root ganglion neurones, suggesting that non-neuronal cells are important for axon growth stimulation.

Animals↗
PubMedDate not supplied

Axons as computing devices: basic insights gained from models.

Detailed models of single neurons are typically focused on the dendritic tree and ignore the axonal tree, assuming that the axon is a simple transmission line. In the last 40 years, however, several theoretical and experimental studies have suggested that axons could implement information processing tasks by exploiting: 1) the time delay in action potential (AP) propagation along the axon; 2) the differential filtering of APs into the axonal subtrees; and 3) their activity-dependent excitability. Models for axonal trees have attempted to examine the feasibility of these ideas. However, because the physiological and anatomical data on axons are seriously limited, realistic models of axons have not been developed. The present paper summarizes the main insights that were gained from simplified models of axons; it also highlights the stochastic nature of axons, a topic that was largely neglected in classical models of axons. The advance of new experimental techniques makes it now possible to pay a very close experimental visit to axons. Theoretical tools and fast computers enable to go beyond the simplified models and to construct realistic models of axons. When tightly linked, experiments and theory will help to unravel how axons share the information processing tasks that single neurons implement.

Algorithms↗
PubMed1999

Schwann cells can induce collateral sprouting from intact axons: experimental study of end-to-side neurorrhaphy using a Y-chamber model.

Axonal regeneration across end-to-side neurorrhaphy has recently been reported; however, neither the mechanism by which collateral sprouting from intact axons is elicited, nor the origin of the regenerating axons are known. There has even been controversy over the presence of collateral axonal sprouting from intact axons altogether. This reported experimental study was designed to clarify these questions. A rat sciatic nerve model was used. To avoid any mechanical damage to the donor nerve during the procedure, a Y-shaped silicone chamber was employed instead of direct suture. Axonal regeneration from the intact tibial nerve across the gap into the peroneal nerve was assessed using a retrograde neurotracer and immunohistochemical staining. Axonal regeneration across the gap was observed in 66 percent of the animals. The neurotracer evaluation clearly showed that all regenerating axons were sensory axons from the dorsal root ganglia. The authors concluded that Schwann cells from the distal wallerian degeneration of nerve segments did elicit collateral axonal sprouting from intact sensory axons, but not from motor axons in end-to-side neurorrhaphy. Invasion of the Schwann cells into the epineurial layer was the crucial step for the initiation of collateral axonal sprouting from the intact axons.

Animals↗
PubMed2000

Uptake of lipoproteins for axonal growth of sympathetic neurons.

Lipoproteins originating from axon and myelin breakdown in injured peripheral nerves are believed to supply cholesterol to regenerating axons. We have used compartmented cultures of rat sympathetic neurons to investigate the utilization of lipids from lipoproteins for axon elongation. Lipids and proteins from human low density lipoproteins (LDL) and high density lipoproteins (HDL) were taken up by distal axons and transported to cell bodies, whereas cell bodies/proximal axons internalized these components from only LDL, not HDL. Consistent with these observations, the impairment of axonal growth, induced by inhibition of cholesterol synthesis, was reversed when LDL or HDL were added to distal axons or when LDL, but not HDL, were added to cell bodies. LDL receptors (LDLRs) and LR7/8B (apoER2) were present in cell bodies/proximal axons and distal axons, with LDLRs being more abundant in the former. Inhibition of cholesterol biosynthesis increased LDLR expression in cell bodies/proximal axons but not distal axons. LR11 (SorLA) was restricted to cell bodies/proximal axons and was undetectable in distal axons. Neither the LDL receptor-related protein nor the HDL receptor, SR-B1, was detected in sympathetic neurons. These studies demonstrate for the first time that lipids are taken up from lipoproteins by sympathetic neurons for use in axonal regeneration.

Animals↗
PubMed1998

Axonal injury caused by focal cerebral ischemia in the rat.

The susceptibility of axons to blunt head injury is well established. However, axonal injury following cerebral ischemia has attracted less attention than damage in gray matter. We have employed immunocytochemical methods to assess the vulnerability of axons to cerebral ischemia in vivo. Immunocytochemistry was performed using antibodies to a synaptosomal-associated protein of 25 kDa (SNAP25), which is transported by fast anterograde transport; the 68-kDa neurofilament subunit (NF68kD); and microtubule-associated protein 5 (MAP5) on sections from rats subjected to 30 min and 1, 2, and 4 h of ischemia induced by permanent middle cerebral artery (MCA) occlusion. After 4 h of occlusion, there was increased SNAP25 immunoreactivity, which was bulbous in appearance, reminiscent of the axonal swellings that occur following blunt head injury. Increased SNAP25 immunoreactivity was present in circumscribed zones in the subcortical white matter and in the axonal tracts at the border of infarction, a pattern similar to that previously described for amyloid precursor protein. Although less marked, similar changes in immunoreactivity in axons were evident following 2 h of ischemia. MAP5 and NF68kD had striking changes in immunoreactivity in axonal tracts permeating the caudate nucleus within the MCA territory at 4 h. The appearance was roughened and disorganized compared with the smooth regular staining in axons within the nonischemic areas. Profiles reminiscent of axonal bulbs were evident in MAP5-stained sections. The changes seen with NF68kD and MAP5 were also evident at 2 h but were more subtle at 1 h. There were no changes in axonal immunoreactivity with SNAP25 or NF68kD at 30 min after MCA occlusion. Altered immunoreactivity following ischemia using SNAP25, MAP5, and NF68kD provides further evidence for the progressive breakdown of the axonal cytoskeleton following an ischemic insult. NF68kD and MAP5 appear to be sensitive markers of the structural disruption of the cytoskeleton, which precedes the subsequent accumulation of SNAP25 within the damaged axons. Axonal cytoskeletal breakdown and disruption of fast axonal transport, which are well-recognized features of traumatic brain injury, are also sequalae of an ischemic insult.

Animals↗
PubMed2006

Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy.

Sensory polyneuropathies are the most frequent neurological complication of human immunodeficiency virus (HIV) infection. Distal symmetric polyneuropathy (DSP), associated with HIV infection, is characterized by length-dependent axonal degeneration of sensory fibres. In rodent dorsal root ganglia (DRG) cultures, HIV viral envelope protein gp120 results in neurotoxicity and axonal degeneration. Since it is unknown whether the axonal degeneration is a consequence of neuronal death or whether it is due to a direct toxic effect on axons, we investigated gp120-induced axonal toxicity using compartmentalized cultures of sensory neurons. Our results show that gp120 causes neuronal apoptosis and axonal degeneration through two, independent and spatially separated mechanisms of action: (i) an indirect insult to cell bodies, requiring the presence of Schwann cells, results in neuronal apoptotic death and subsequent axonal degeneration; (ii) a direct, local toxicity exerted on axons through activation of mitochondrial caspase pathway that is independent of cell body. This local axonal toxicity is mediated through binding of gp120 to axonal chemokine receptors and can be prevented by chemokine receptor blockers. In conclusion, we propose a novel pathway of axonal degeneration mediated by gp120 that is dependent on local activation of caspases in the axon. This observation suggests that axonal protection is a relevant therapeutic target for HIV-associated sensory neuropathy. Furthermore, chemokine receptor inhibitors, which are currently being developed as HIV entry inhibitor drugs, may also have a therapeutic role in HIV-associated peripheral neuropathies by preventing axonal degeneration.

Animals↗
PubMed1993

A high degree of spatial selectivity in the axonal and dendritic domains of physiologically identified local-circuit neurons in the dentate gyrus of the rat hippocampus.

The axonal and dendritic domains of neurons with extensive, locally arborizing axons were delineated in the dentate gyrus of the rat hippocampus. In horizontally cut slice preparations neurons were briefly recorded and subsequently filled with biocytin when one or several of the following physiological properties were observed: (i) high-amplitude short-latency spike afterhyperpolarization; (ii) lack of spike frequency adaptation; (iii) high firing rate in response to depolarizing current. In a sample of 14 neurons, sufficient dendritic and/or axonal detail was recovered to identify them as non-principal cells, i.e. non-granule, non-mossy cells. Five distinct types of cells were recognized, based on the spatial distribution of dendrites, presumably reflecting the availability of afferents, and on the basis of the highly selective distribution of their axon terminals, indicating synaptic target selectivity. They are: (1) the hilar cell forming a dense axonal plexus in the commissural and association pathway terminal field (HICAP cell; horizontal axon extent 1.6 mm) in the inner one-third of the molecular layer, and having dendrites extending from the hilus to the top of the molecular layer; (2) the hilar cell with its axon ramifying in the perforant path terminal field (HIPP cell, horizontal axon extent 2.0 mm) in the outer two-thirds of the molecular layer, whereas its spiny dendrites were restricted to the hilus; (3) the molecular layer cell with its dendritic and axonal domains confined to the perforant path terminal zone (MOPP cell, horizontal extent of axon 2.0 mm); (4) the dentate basket cell (horizontal axon extent 0.9 mm) had most of its axon concentrated in the granule cell layer, the remainder being localized in the inner molecular layer and hilus; (5) the hilar chandelier cell, or axo-axonic cell (horizontal axon extent 1.1 mm), densely innervating the granule cell layer with fascicles of radially oriented terminal rows, and also forming an extensive plexus in the hilus. The three cell types having their somata in the hilus projected to granule cells at the same septo-temporal level where their cell bodies were located. The results demonstrate that there is a spatially selective innervation of the granule cells by at least five distinct types of dentate neurons, which terminate in several instances in mutually exclusive domains. Their dendrites may have access to all (HICAP cell) or only a few (e.g. HIPP and MOPP cell) of the hippocampal afferents. This arrangement provides a framework for independent interaction between the output of local circuit neurons and subsets of excitatory afferents providing input to principal cells.

Animals↗
PubMed2004

A soluble Nogo receptor differentially affects plasticity of spinally projecting axons.

In the central nervous system, regeneration of injured axons and sprouting of intact axons are suppressed by myelin-derived molecules that bind to the Nogo receptor (NgR). We used a soluble form of the NgR (sNgR), constructed as an IgG of the human NgR extracellular domain, to manipulate plasticity of uninjured primary afferent and descending monoaminergic projections to the rat spinal cord following dorsal rhizotomy. Rats with quadruple dorsal rhizotomies were treated with intrathecal sNgR or saline, or were left untreated for 2 weeks. Rhizotomy alone resulted in sprouting of serotonergic axons and to a lesser extent, tyrosine-hydroxylase (TH)-expressing axons, while axons expressing dopamine-beta-hydroxylase (DbetaH) were unaffected. Human IgG immunohistochemistry revealed that sNgR infused into the intrathecal space penetrated approximately 300 microm into spinal white and grey matter. Separate axonal populations differed in their responses to intrathecal sNgR: TH-expressing and DbetaH-expressing axons responded most and least vigorously, respectively. Serotonergic axons were identified by serotonin (5-HT) or serotonin transporter (SERT) immunohistochemistry. Interestingly, a large increase in 5-HT compared to SERT-positive axons density in both saline and sNgR-treated rats indicated that serotonergic axons both sprouted and increased their transmitter content in response to rhizotomy and sNgR treatment. Calcitonin gene-related peptide-positive axons were largely depleted ipsilaterally by rhizotomy, and sNgR increased axon density only in deeper contralateral laminae (III-V). GAP-43 immunohistochemistry revealed a small increase in axon density following dorsal rhizotomy that was further augmented by sNgR treatment. These results reveal a differential effect of myelin antagonism on distinct populations of spinally projecting axons.

Animals↗
PubMed1968

Conduction failure in myelinated and non-myelinated axons at low temperatures.

1. The effects of low temperature on conduction in single myelinated and non-myelinated axons of the feline saphenous nerve were examined and compared. Nerves were cooled by a conventional thermode, but thermal gradients were minimized by an insulating layer of agar-saline gel over the nerve and the face of the thermode.2. The mean blocking temperature of thirty-one non-myelinated axons, 2.7 degrees C, was significantly lower than that of 111 myelinated axons, 7.2 degrees C. No evidence for a differential block of myelinated axons according to their normal conduction velocity could be demonstrated.3. Reductions in the proportional conduction velocities of both myelinated and non-myelinated axons were nearly identical between 17 and 37 degrees C. However, below 17 degrees C the rate at which the proportional conduction velocity of the non-myelinated axons fell during cooling was significantly less than for the myelinated axons and was sufficient to account for their lower blocking temperatures. As a result, critical minimum conduction velocities were reached at higher temperatures in myelinated axons than in non-myelinated axons.4. The conduction velocity of successive impulses in a train slowed progressively to a constant value which depended on the frequency of stimulation. Consequently, the early impulses were separated by intervals that exceeded those between stimuli and were not affected by temperatures that blocked later impulses. The pattern of block was consistent with an increasing refractoriness of the axons as the temperature fell.5. The maximal frequency of discharge that myelinated axons could carry at temperatures between normal and 12 degrees C was related directly to fibre size. Non-myelinated axons could conduct low frequency trains of impulses at temperatures that blocked such activity in myelinated axons. In all axons, high frequency trains of impulses could be completely blocked at temperatures which permitted lower frequency trains to pass uninterrupted.6. Hysteresis in the blocking temperatures of axons was related to the hysteresis in their conduction velocities.

Agar↗
PubMed1978

Evoked depolarizing and hyperpolarizing potentials in reticulospinal axons of lamprey.

1. Intracellular recordings were made from reticulospinal axons (Müller axons) in the lamprey spinal cord. Electrical stimuli applied to the spinal cord surface elicited depolarizing and hyperpolarizing 'synaptic-like' potentials in Müller axons. The physiological basis of these evoked potentials was investigated. 2. The depolarizing response was not the result of increased extracellular K, as demonstrated by the constancy of the undershoot of the axonal action potential during the depolarization, by the failure of the response to summate during repetitive stimulation and by the failure of the response amplitude to vary as predicted when the [K] of the saline was varied. 3. When the membrane potential of the axon was varied by passing current through a micro-electrode, the amplitude of the depolarizing evoked potential decreased at membrane potentials positive to the resting potential and increased up to a maximum when the axon was hyperpolarized by about 10 mV. The extrapolated 'reversal potential' for the depolarizing response was about 15 mV positive to the normal -80 mV resting potential of the axon. However, the amplitude of the response did not continue to grow with hyperpolarizations greater than 10 mV, and, thus, the response did not behave as would a normal depolarizing synaptic potential. 4. Müller axons make numerous electrical synapses with spinal motoneurones and interneurones, and this suggested that the depolarizing response might be a coupling potential. In agreement with this idea, quantitative correspondence was found between changes in the input resistance of the axon produced by the depolarizing response and the variation in the depolarizing response amplitude. Thus, although the depolarizing response mimicked in some ways the behaviour of an excitatory synaptic potential, we conclude that it is a coupling potential. 5. The hyperpolarizing response also appeared to be a coupling potential. Its amplitude was not changed by hyperpolarizing the axon up to 30 mV and was decreased by depolarizing the axon sufficiently to decrease the axon's input resistance. 6. It is proposed that both depolarizing and hyperpolarizing evoked potentials in lamprey Müller axons are a result of passive flow of current from cells activated by the spinal cord stimulus and electrically coupled to Müller axons.

Animals↗
PubMed1988

The axon terminal of goldfish retinal horizontal cells: a low membrane conductance measured in solitary preparations and its implication to the signal conduction from the soma.

1. Mechanical dissociation of the enzyme-treated goldfish retina yielded somata and axon terminals of horizontal cells. The membrane properties of these solitary axon terminals were investigated using the whole-cell patch-clamp technique. 2. Axon terminals had a large input resistance, comparable to the seal resistance (approximately 30 G omega). Most axon terminals (greater than 80%) showed a nearly linear current-voltage relation between -60 and +10 mV, where the slope conductance was as small as 5 muS/cm2. Some axon terminals showed a shallow negative slope conductance in the same potential range. 3. The membrane current consisted of two components: transient and sustained. The transient component was carried by sodium ions, and the sustained component was a mixture of calcium and potassium currents. The sodium current (INa) was activated by depolarization of beyond -45 mV and was maximal (approximately 60 pA) at -10 mV. It was blocked by 5 microM tetrodotoxin and disappeared in Na+-free medium. The maximum amplitude of INa was less than 10% of INa of the soma. 4. A small calcium current (less than 6 pA) was isolated in a small proportion of cells, with an amplitude approximately 5% of the calcium current evoked in the soma under the identical recording conditions. 5. A small amount of potassium current through the anomalous rectifier was induced in the axon terminal when the membrane potential was below -60 mV. Its conductance was 15-20 muS/cm2, only 1/20 of the estimate in the soma. Other types of potassium currents were not detected. 6. It is concluded that the soma and the axon terminal have a similar set of membrane currents, but the specific membrane conductance of the axon terminal is extremely low. The signal conductivity from soma to axon terminal was assessed using a passive cable model together with numerical values obtained from the present experiments. Although the membrane conductance of the connecting axon was not measurable directly, the calculation strongly suggests that low conductance of the axon terminal membrane minimizes the leakage of signals arriving electrotonically through the thin connecting axon, even if the membrane conductance of the axon was overestimated as being identical to the soma membrane. 7. These results can explain why light-evoked responses recorded from the axon terminal are similar in amplitude as well as in waveform to those recorded from the soma, despite the lack of direct inputs from photoreceptors.

Animals↗
PubMed1990

Identification of early developing axon projections from spinal interneurons in the chick embryo with a neuron specific beta-tubulin antibody: evidence for a new 'pioneer' pathway in the spinal cord.

The early development of interneurons in the chick embryo spinal cord was studied using a monoclonal antibody against a neuron-specific beta-tubulin isoform. Early developing interneurons were divided into two cell groups on the basis of their location and the pattern of growth of their axons. One group is composed of cells that establish a primitive longitudinal pathway (PL-cells), whereas the other group contains cells constituting a circumferential pathway (C-cells). The onset of axonal development in both cell groups occurs at stage (st.) 15 (embryonic day, (E), 2) in the branchial segments, which is prior to axonogenesis of motoneurons. PL-cells develop in the region between the floor plate and the motoneuron nucleus. Their axons are the first neuronal processes ('pioneer axons') to arrive in the ventrolateral marginal zone and they project both rostrally and caudally to establish a primitive longitudinal association pathway at the ventrolateral surface of the neural tube. This pathway is formed before axons of C-cells arrive in the ventrolateral region. The first C-cells are initially located in the most dorsal portion of the neural tube, whereas later appearing C-cells are also located in both intermediate and ventral regions of the neural tube. The axons of C-cells project ventrally, without fasciculating, along the lateral border of the neural tube. Some of their axons enter the ipsilateral ventrolateral longitudinal pathway at st. 17. We often observed apparent contacts and interactions between preexisting axons of PL-cells and newly arriving axons of C-cells. The axons of commissural C-cells first enter the floor plate at st. 17 and cross the midline at st. 18. Axons of C cells begin to join the contralateral ventrolateral longitudinal pathway at st. 18+ to st. 19. In the floor plate region, contacts between growth cones and axons were often observed. However, axons in the floor plate at these stages were not fasciculated. These observations establish the timing and pattern of growth of axons from two specific populations of early developing interneurons in the chick spinal cord. Additionally, we have identified an early and apparently previously undescribed 'pioneer' pathway that constitutes the first longitudinal pathway in the chick spinal cord.

Animals↗
PubMed2000

Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics.

During development of the adult Drosophila visual system, axons of the eight photoreceptors in each ommatidium fasciculate together and project as a single bundle towards the optic lobes of the brain. Within the brain, individual photoreceptor axons from each bundle then seek specific targets in distinct layers of the optic lobes. The axons of photoreceptors R1-R6 terminate in the lamina, while R7 and R8 axons pass through the lamina to terminate in separate layers of the medulla. To identify genes required for photoreceptor axon guidance, including those with essential functions during early development, we have devised a strategy for the simple and efficient generation of genetic mosaics in which mutant photoreceptor axons innervate a predominantly wild-type brain. In a large-scale saturation mutagenesis performed using this system, we recovered new alleles of the gene encoding the receptor tyrosine phosphatase PTP69D. PTP69D has previously been shown to function in the correct targeting of motor axons in the embryo and R1-R6 axons in the visual system. Here, we show that PTP69D is also required for correct targeting of R7 axons. Whereas mutant R1-R6 axons occasionally extend beyond their normal targets in the lamina, mutant R7 axons often fail to reach their targets in the medulla, stopping instead at the same level as the R8 axon. These targeting errors are difficult to reconcile with models in which PTP69D plays an instructive role in photoreceptor axon targeting, as previously proposed. Rather, we suggest that PTP69D plays a permissive role, perhaps reducing the adhesion of R1-R6 and R7 growth cones to the pioneer R8 axon so that they can respond independently to their specific targeting cues.

Amino Acid Sequence↗