Subplate neurons pioneer the first axon pathway from the cerebral cortex

During the development of the nervous system, growing axons must traverse considerable distances to find their targets. In insects, this problem is solved in part by pioneer neurons, which lay down the first axonal pathways when distances are at a minimum. Here the existence of a similar kind of neuron in the developing mammalian telencephalon is described. These are the subplate cells, the first postmitotic neurons of the cerebral cortex. Axons from subplate neurons traverse the internal capsule and invade the thalamus early in fetal life, even before the neurons of cortical layers 5 and 6, which will form the adult subcortical projections, are generated. During postnatal life, after the adult pattern of axonal projections is firmly established, most subplate neurons disappear. These observations raise the possibility that the early axonal scaffold formed by subplate cells may prove essential for the establishment of permanent subcortical projections.     

Regulation of neurotrophin-3 expression by epithelial-mesenchymal interactions: the role of Wnt factors

Neurotrophins regulate survival, axonal growth, and target innervation of sensory and other neurons. Neurotrophin-3 (NT-3) is expressed specifically in cells adjacent to extending axons of dorsal root ganglia neurons, and its absence results in loss of most of these neurons before their axons reach their targets. However, axons are not required for NT-3 expression in limbs; instead, local signals from ectoderm induce NT-3 expression in adjacent mesenchyme. Wnt factors expressed in limb ectoderm induce NT-3 in the underlying mesenchyme. Thus, epithelial-mesenchymal interactions mediated by Wnt factors control NT-3 expression and may regulate axonal growth and guidance.     

"Caudated-induced" cortical potentials: comparison between monkey and cat

The segment of the internal capsule which carries axons relating to the sensorimotor cortex does not closely adjoin the caudate in the monkey as it does in the cat. Therefore, in seeking evidence for caudate-induced cortical responses, activation of the adjoining internal capsule by stimulus spread can be avoided. In the monkey, caudate stimulation never produced cortical responses, and only capsule stimulation evoked the potential complex which has been attributed to caudate stimulation in the cat.     

Axonal proteins of presynaptic neurons during synaptogenesis

Changes occur in the synthesis and axonal transport of neuronal proteins in dorsal-root ganglia axons as a result of contact with cells from the spinal cord during synapse formation. Dorsal-root ganglia cells were cultured in a compartmental cel culture system that allows separate access to neuronal cell bodies and their axons. When cells from the ventral spinal cord were cultured with the dorsal-root ganglia axons, synapses were established within a few days. Metabolic labeling and two-dimensional electrophoresis revealed that four of more than 300 axonal proteins had changed in their expression by the time synapses were established. The highly selective nature of these changes suggests that the proteins involved may be important in the processes of axon growth and synapse formation and their regulation by the regional environment.     

Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway

Regenerating sensory axons in the dorsal roots of adult mammals are stopped at the junction between the root and spinal cord by reactive astrocytes. Do these cells stop axonal elongation by activating the physiological mechanisms that normally operate to stop axons during development, or do they physically obstruct the elongating axons? In order to distinguish these possibilities, the cytology of the axon tips of regenerating axons that were stopped by astrocytes was compared with the axon tips that were physically obstructed at a cul-de-sac produced by ligating a peripheral nerve. The terminals of the physically obstructed axon tips were distended with neurofilaments and other axonally transported structures that had accumulated when the axons stopped elongating. By contrast, neurofilaments did not accumulate in the tips of regenerating axons that were stopped by spinal cord astrocytes at the dorsal root transitional zone. These axo-glial terminals resembled the terminals that axons make on target neurons during normal development. On the basis of these observations, astrocytes appear to stop axons from regenerating in the mammalian spinal cord by activating the physiological stop pathway that is built into the axon and that normally operates when axons form stable terminals on target cells.     

Neuronal properties of nymphal and adult insect neurosecretory cells in vitro

Neurosecretory brain cells from late nymphal and adult cockroaches were grown for 1 to 3 months in a chemically defined medium in combined cultures with embryonic organs or oocytes from nymphal and adult specimens. Under these conditions, neurosecretory cells show vigorous axonal growth. Electron dense granules in cell perikarya and axons of 3-month-old cultures are suggestive of neurosecretory activity in vitro.     

Slow transport of tubulin in the neurites of differentiated PC12 cells

In order to study the rate and form of tubulin transport in cultured neuronal cells, the fluorescence recovery after the photobleaching of a fluorescent tubulin analog has been followed within the neuritic processes of differentiated PC12 cells. In these cells, as in peripheral axons, tubulin is transported in coherent, nondiffusing waves at two different slow rates that are within the range of the slow components a and b of axonal transport measured in vivo. Finally, it appears that most, if not all, of the tubulin analog is moving out these processes. Thus, slow neuroplasmic transport in cultured neuron-like cells is a good model of axonal transport, in which experimental manipulations of the system can be performed that would be difficult in the whole animal.     

A glial-neuronal signaling pathway revealed by mutations in a neurexin-related protein

In the nervous system, glial cells greatly outnumber neurons but the full extent of their role in determining neural activity remains unknown. Here the axotactin (axo) gene of Drosophila was shown to encode a member of the neurexin protein superfamily secreted by glia and subsequently localized to axonal tracts. Null mutations of axo caused temperature-sensitive paralysis and a corresponding blockade of axonal conduction. Thus, the AXO protein appears to be a component of a glial-neuronal signaling mechanism that helps to determine the membrane electrical properties of target axons.     

Cell recognition during neuronal development

Insect embryos, with their relatively simple nervous systems, provide a model system with which to study the cellular and molecular mechanisms underlying cell recognition during neuronal development. Such an approach can take advantage of the accessible cells of the grasshopper embryo and the accessible genes of Drosophila. The growth cones of identified neurons express selective affinities for specific axonal surfaces; such specificities give rise to the stereotyped patterns of selective fasciculation common to both species. These and other results suggest that early in development cell lineage and cell interactions lead to the differential expression of cell recognition molecules on the surfaces of small subsets of embryonic neurons whose axons selectively fasciculate with one another. Monoclonal antibodies reveal surface molecules in the Drosophila embryo whose expression correlates with this prediction. It should now be possible to isolate the genes encoding these potential cell recognition molecules and to test their function through the use of molecular genetic approaches in Drosophila.     

Cdh1-APC controls axonal growth and patterning in the mammalian brain

The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific growth of granule neuron axons and parallel fiber patterning. Cdh1 RNA interference in neurons was also found to override the inhibitory influence of myelin on axonal growth. Thus, Cdh1-APC appears to play a role in regulating axonal growth and patterning in the developing brain that may also limit the growth of injured axons in the adult brain.     

Lesion-induced sprouting in the rat dentate gyrus is inhibited by repeated ethanol administration

The effect of ethanol on hippocampal axonal sprouiting was studied with a histochemical technique for identifying acetylcholinesterase. Unilateral lesion of the entorhinal cortex in adult rats produced an increase in the density of acetylcho-linesterase staining in the outer molecular layer and a concomitant increase in the width of the pale-staining commissural-associational zone of the dentate gyrus. Other rats were given ethanol (11.3 +/- 0.45 grams per kilogram) for 2 weeks before and 9 days after receiving the lesion. Ethanol abolished the expansion of the commissural-associational zone. The effect of ethanol on sprouting axons suggests that it may inhibit recovery of function after brain injury.     

A strong influence of serotonin axons on beta-adrenergic receptors in rat brain

The role of serotonin axons in modulating the norepinephrine neurotransmission system in rat brain was investigated. Selective lesions of the forebrain serotonergic system were made by injecting 5,7-dihydroxytryptamine into the midbrain raphe nuclei. Four to six weeks after the lesion, the uptake of 3H-labeled serotonin in the frontal cortex and the hippocampus was reduced by more than 90 percent, while neither the uptake of 3H-labeled norepinephrine nor the content of norepinephrine was affected in either tissue. The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions. Similarly, specific lesions of central serotonin axons produced by systemically administered p-chloramphetamine resulted in an increase in the binding of 3H-labeled dihydroalprenolol to beta-adrenergic receptors and in the production of adenosine 3',5'-monophosphate in response to isoproterenol. These results indicate that serotonin axons may regulate beta-adrenergic receptor number and function in brain.     

Acute axonal dystrophy caused by fluorocitrate: the role of mitochondrial swelling

Fluorocitrate, a Krebs cycle inhibitor, induices neurons to rapidly expel multitudinous lysosomes, mitochondria, and other cytoplasmic constituents into their axons. After convulsive seizures commence, spectacular axonal balloons develop owing to obstruction of axonal flow by "log jams" of extruded organelles. A swelling of neuronal mitochondria is apparently responsible for the disgorgement of cytoplasmic material into axons.     

恒河猴胸腺的显微与超微结构观察

应用组织学、组织化学和透射电镜技术观察表明，恒河猴胸腺外包被膜，被膜结缔组织伸入其内部形成许多小隔，将胸腺实质分成许多小叶，小叶又由皮质和髓质组成，大部分的髓质彼此相连，被膜和小叶间隔内含有较多的肥大细胞。皮质主要由幼稚T细胞和皮皮细胞构成，另有少量的巨噬细胞和肥大细胞等；皮人还可见典型的血－胸腺屏障。髓质主要由成熟T细胞和上皮细胞组成，另有较多的肥大细胞和少量的巨噬细胞、交错突细胞、B淋巴细胞、浆细胞、嗜酸性粒细胞、肌样细胞以及一些胸腺小体和胸腺小囊。     

Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex

The functional and anatomical rearrangements of cortical sensory maps accompanying changes in experience are not well understood. We examined in vivo and in vitro how the sensory map and underlying synaptic connectivity of the developing rat barrel cortex are altered when the sensory input to the cortex is partially deprived. In the nondeprived cortex, both the sensory responses and synaptic connectivity between columns were strengthened through an increase in the synaptic connection probability between L2/3 pyramids in adjacent columns. This was accompanied by a selective growth of L2/3pyramid axonal arbors between spared columns. In contrast, deprived and nondeprived cortical columns became weakly connected in their L2/3 pyramid connections.     

Preferred microtubules for vesicle transport in lobster axons

The hypothesis that transported vesicles are preferentially associated with a subclass of microtubules has been tested in lobster axons. A cold block was used to collect moving vesicles in these axons; this treatment caused the vesicles to accumulate in files along some of the microtubules. Quantitative analysis of the number of vesicles associated with microtubule segments indicated that lobster axons have two distinct populations of microtubules--transport microtubules that are the preferred substrates for vesicle transport and architectural microtubules that contribute to axonal structure.     

Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats

The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as "bridges" between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.     

Human amnion membrane serves as a substratum for growing axons in vitro and in vivo

The epithelial cell layer of human amnion membrane can be removed while the basement membrane and stromal surfaces remain morphologically intact. Such a preparation has been used as a substratum for the in vitro culture of dissociated neurons. Embryonic motor neurons from chick ciliary ganglion attached to both surfaces but grew extensive neurites only on the basement membrane. On cross sections of rolled amnion membranes, regenerating axons of cultured neurons were guided along pathways of basement membrane that were immunoreactive with an antibody to laminin. In addition, when rolled amnion membranes were implanted into a lesion cavity between the rat septum and hippocampus, cholinergic neurons extended axons through the longitudinally oriented implant into the hippocampus. Thus, this amnion preparation can serve as a bridge to promote axonal regeneration in vivo in damaged adult brain.     

An in vitro neurite-promoting antigen functions in axonal regeneration in vivo

The function of the neurite growth-promoting antigen INO has been tested in an in vivo neurite regeneration system, the rat iris. The sympathetic innervation of the irides was removed by a single systemic injection of 6-hydroxydopamine. The subsequent regeneration of sympathetic axons into the iris of one eye bathed by the INO antibody, which inhibits neurite growth in vitro, was compared with the regrowth of sympathetic axons into the iris of the animal's other eye, which contained control antibody. Antibodies were released within the eye by implanted hybridoma cells. Neurite regeneration was measured by assaying [3H]norepinephrine uptake into freshly explained irides. The blockage of the function of the INO antigen by the antibody resulted in a decreased rate of axonal regeneration, thus suggesting the involvement of the INO antigen in the process of neurite regeneration in vivo.     

Action-potential modulation during axonal conduction

Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.