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N R Smalheiser

Publications and source records attributed to N R Smalheiser.

44 records · Page 3Linked to original sources
PubMed1984

The possible role of "sibling neurite bias" in the coordination of neurite extension, branching, and survival.

In this review we consider a novel mechanism, "sibling neurite bias," which may explain aspects of the coordination of elongation, branching, and resorption among different neurites growing from the same neuronal cell body. In this model, growing neurites which incorporate structural precursors at higher rates would deplete the cellular pool of precursors available to their "sibling" neurites; neurites would compete for survival, but in addition they would bias each other's behavior during active growth. Evidence is reviewed that "sibling neurite bias" may contribute to the establishment and stabilization of specific neural connections. Specific examples examined include the loss of polyinnervation at the developing neuromuscular junction, contextual mapping in the retino-tectal system, and selective neurite growth patterns and synaptic connections in nerve tissue culture model systems.

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PubMed1984

Radiosensitivity and differentiation of ganglion cells within fetal mouse retinal explants in vitro.

Fetal mouse retinas were explanted at 13-14 days of gestation, and exposed to gamma radiation in vitro. Not all regions of the retina were equally susceptible to radiation-induced necrosis; when exposed to 5000 rads soon after explanation, each explant had a single small radioresistant nubbin of apparently intact tissue, located near the optic nerve-head. This region of radioresistant tissue was larger when the dose of radiation was reduced and when the explants were exposed at later times in vitro, indicating the existence of a gradient of radioresistance across retinal explants which spread outward through at least the first week in vitro, the period examined. Based upon the extensive in situ literature which has correlated the emergence of radioresistance with the differentiation of retinal neurons, we conclude that the in situ central-to-peripheral sequence of cellular differentiation continues in vitro within our retinal explants. Whereas the ganglion cell axonal outgrowth from control retinas grown in isolation on collagen substrates underwent a gradual disintegration over 3 weeks in vitro, the sparse axonal outgrowth from explants exposed to 5000 rads disintegrated abruptly at 5-7 days in vitro. This did not appear to be due to direct damage from radiation, but instead reflected the fact that axons in irradiated cultures arose from central retinal regions only, while many axons in control cultures emerged from later-differentiating peripheral regions. We suggest that disintegration of individual axons in the outgrowth may occur rapidly and in a central-to-peripheral sequence. These findings should be useful in designing assays for trophic factors which may prevent ganglion cell axon disintegration in this in vitro model system.

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PubMed1984

Laminin as a substrate for retinal axons in vitro.

Fetal mouse retinal ganglion cell axons have been shown to ramify within co-cultured basement membrane secreting tumor explants and upon isolated basement membranes. Here we report that laminin, a glycoprotein found in basement membranes and adhesion sites of a variety of cell types, acted as a substrate for retinal explant attachment and axonal outgrowth. When axons were given a direct choice, laminin was preferred over collagen. Under suitable conditions (air-dried upon underlying collagen gels), laminin was more effective than fibronectin for promoting axon emergence from retinal explants. These findings have implications for the study of molecular mechanisms underlying CNS axonal outgrowth.

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PubMed1981

Positional specificity tests in co-cultures of retinal and tectal explants.

In previous studies we demonstrated that HRP-labeled ganglion-cell axons arising from fetal mouse retinal explants can distinguish appropriate (tectum) from inappropriate (spinal cord) CNS target regions in vitro. Retinal fibers preferentially invade the tectum where they ramify, develop terminal arbors, and make functional connections. The present study attempts to determine if fibers from a half-retina prefer the 'appropriate' half-region of a tectal explant. In one series, nasal or temporal halves were placed near the medial edge of the tectum, to test turning toward or away from the appropriate (posterior or anterior) half-tectal region. Several co-cultures showed apparent preferences, especially those with many ingrowing retinal fibers; but in other co-cultures the data were equivocal. A second paradigm placed the half-retinas near anterior or posterior tectal edges, and simply scored presence vs absence of retinal fiber ramifications within the nearest tectal half-region. This identified entry of retinal fibers into appropriate vs inappropriate half-tectal regions in 8 out of 8 blind scorings. These data encourage further, more critical analyses of retinotectal co-cultures to explore the basis of the specific neuritic connections which form in situ.

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PubMed1981

Neurites from mouse retina and dorsal root ganglion explants show specific behavior within co-cultured tectum or spinal cord.

We have utilized extracellular microiontophoretic injections of horseradish peroxidase into fetal mouse retinal explants to label retinal ganglion cell axons innervating co-cultured tectal explants in a solid Golgi-like manner. Using dorsal root ganglia-tectum and retina-spinal cord co-cultures as controls, our results indicate that retinal neurites show selective growth and arborizations within their appropriate tectal, target tissue. Retinotectal explant co-cultures may be a useful model system for studying aspects of neuronal specificity.

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PubMed1981

Development of ganglion cells and their axons in organized cultures of fetal mouse retinal explants.

Retinas from 13-15 day fetal mice were explanted alone, with adjacent eyeball tissue, or with nearby superior colliculus explants. The organotypic structure of the retina developed in situ, including photoreceptors, interneurons, plexiform layers, ganglion cells, and an optic fibre layer. Electrophysiologic recordings demonstrated that functional synaptic networks developed resembling bioelectric response patterns seen in situ. Within half-retinas, arrays of optic fibers converged to the optic nerve head; in co-cultures with tectum they could become myelinated. Large bundles of long, naked neurites--1 degree primary retinal fibers--emerged from the explant in the first few days in vitro; these could often be traced back to the optic nerve head and a detailed survey of their properties using horseradish peroxidase (HRP) tracing methods identified tham as ganglion cell axons. When growing upon collagen substrata, 1 degree fibers began to disintegrate during the second week in vitro; however, many 1 degree fibers that grew into superior colliculus explants were maintained for at least 5 weeks in vitro, where they formed elaborate, functional terminal arborizations. In a few cases, 1 degree fibers grew across skeletal muscle fibers and appeared to induce them to contract. A second type of neuritic outgrowth pattern appeared after the first week in vitro: 2 degrees retinal fibers. This was composed of a mixed population of interneuronal neurites; a small percentage was catecholaminergic. Our characterization of the morphologic properties of retinal ganglion cells and their axons in organotypic cultures provides the necessary background to interpret electrophysiologic mapping and neural-specificity analyses of retino-CNS co-cultures. This in vitro model system may have biological relevance to understanding the cues that control the development of the retinotectal projection in situ.

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PubMed1981

Specific neuritic pathways and arborizations formed by fetal mouse dorsal root ganglion cells within organized spinal cord explants in culture: a peroxidase-labeling study.

Extracellular microiontophoretic injections of horseradish peroxidase (HRP) into NGF-enhanced fetal mouse dorsal root ganglia (DRGs) produced an anterograde solid Golgi-like labeling of DRG neurites and their terminal arborizations within co-cultured spinal cord explants. In cultures of spinal cord transverse cross-sections with attached DRGs, the large NGF-enhanced DRGs remained in close proximity to the cord, often adjacent to both dorsal and ventral cord regions. Despite this, nearly all DRG neurites that entered the cord did so via dorsal root fascicles. They branched and ramified extensively within the dorsal region, taking on a wavy or kinky course and showed various types of arborizations. The density of cord innervation was much lower when isolated DRGs and cord explants were co-cultured 0.5-1 mm apart. Although fewer entering DRG fibers were labeled by our HRP injections the same qualitative growth and arborization patterns were seen within dorsal and ventral cord regions as in explants of cord with attached DRGs. When the facing edge contained both dorsal and ventral tissues, HRP-labeled DRG fibers entered dorsal regions selectively. DRG fibers readily entered, ramified and arborized within isolated strips of dorsal cord, whereas they sharply avoided isolated ventral cord explants. The avoidance of ventral cord cannot simply be due to the paucity of specific synaptic targets within the tissue, for larger numbers of DRG fibers entered completely inappropriate CNS target tissues, e.g. superior colliculus explants--though they did not ramify or arborize to any degree comparable to that seen within dorsal cord regions.

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