Converting an American Optical ophthalmoscope handle to use standard C batteries.
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Electric Power Supplies↗
Biomedical subjects
J E Cook
Publications and source records attributed to J E Cook.
Independent mosaics of large inner- and outer-stratified ganglion cells in the goldfish retina.
Goldfish retinal ganglion cells were filled with horseradish peroxidase and studied in flatmounts. Two regular mosaics of large neurons with many of the properties of mammalian alpha ganglion cells were found, differing from each other in spacing, size, and dendritic stratification. The existence of biplexiform ganglion cells with additional dendrites in the outer plexiform layer was also confirmed. One of the two alpha-like mosaics consisted of giant ganglion cells with thick primary dendrites and large, sparsely branched dendritic trees in the outer sublamina of the inner plexiform layer (IPL). In fish 55-65 mm long, about 300 formed a tessellated array across each retina. Their somata (mean area 277 +/- 6 microns 2) were displaced to varying degrees into the IPL, neighbours in the mosaic often occupying different levels. Their dendrites ramified in one stratum near the inner nuclear layer, at a mean depth of 70.8 +/- 0.5% of the IPL. The other alpha-like mosaic comprised about 900 large ganglion cells, with slightly smaller somata (mean area 193 +/- 4 microns 2) in the ganglion cell layer. Most of their dendrites lay in a narrow stratum at 41.9 +/- 0.5% of the depth of the IPL. However, deviations (usually into more vitread strata) were common, which was not true for similar cells in the distantly related cichlid fish Oreochromis. Measurements of nearest neighbour distance (NND) for 4 outer and 4 inner mosaics showed that they were at least as regular as the alpha cell mosaics of mammals: the ratio of the mean NND to the standard deviation ranged from 4.03 for the least regular outer mosaic to 6.47 for the most regular inner mosaic. The wide phylogenetic distribution of these paired, regular mosaics points to a fundamental role in vision. The presence of some variability in dendritic stratification even within the exceptionally regular inner-stratified mosaic suggests that classifications based entirely on the detailed morphology of individual neurons may not always correlate well with their primary functional roles. Where possible, neuronal morphology and spatial distribution should be studied together.
Animals↗
Sclerosing peritoneal mesothelioma in a dog evaluated by electron microscopy and immunoperoxidase techniques.
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Animals↗
Chronic pyridostigmine bromide administration: side effects among soldiers working in a desert environment.
The side effects of chronic pyridostigmine bromide administration were studied in seven male soldiers performing moderate-intensity exercise in a desert environment. A 2-week, double-blind, placebo-controlled crossover design was employed in which pyridostigmine was administered for 7 consecutive days (30 mg orally, t.i.d.). Four hours each day were spent in the heat (42 degrees C, 20% relative humidity); 2 hours rest followed by 2 hours moderate exercise (40% maximal aerobic power). Each day, subjects completed four symptom questionnaires and received three focused physical examinations. Symptoms reported did not differ between treatment groups except for fewer headaches during pyridostigmine treatment. Soldiers were unable to distinguish the effects of pyridostigmine from placebo. Pyridostigmine was associated with lower resting diastolic blood pressure (approximately 4 mmHg, p less than 0.05), smaller pupil diameter (approximately 0.5 mm, p less than 0.01), decreased handgrip strength (approximately 3%, p less than 0.05), and higher final rectal temperature (approximately 0.1 degree C, p less than 0.01). Effects of this magnitude are not likely to appreciably limit performance. We conclude that chronic pyridostigmine administration does not negatively impact on soldiers' ability to perform physical work over repeated days in a desert environment.
Adolescent↗
Regular mosaics of large displaced and non-displaced ganglion cells in the retina of a cichlid fish.
Large retinal ganglion cells in the tilapid cichlid fish Oreochromis spilurus (standard length 15-54 mm) were filled with horseradish peroxidase and studied in flatmounts. Three types, with distinct patterns of dendritic stratification, formed spatially independent, nonrandom mosaics. One type (about 0.3% of all ganglion cells) resembled the outer (off) alpha cells of mammals. They were very large, with thick primary dendrites and large, sparsely branched planar trees in the outer part of the inner plexiform layer (IPL). About 300 were arrayed regularly across each retina, their exact number and spacing depending on its size. Their somata were often displaced into the IPL, even where neighbours in the mosaic were orthotopic. Another type (0.8%) resembled the inner (on) alpha cells of mammals. These had slightly smaller somata that were never displaced and smaller trees in the middle layers of the IPL. About 800 were arrayed uniformly and regularly across each retina. A rarer type (0.06-0.08%) had two planar trees: one forming a coarse mosaic in the outer part of the inner plexiform layer (co-planar with the trees of outer alpha-like cells) and another in the outer plexiform layer. These "biplexiform" cells were smaller and rounder than alpha-like cells and always displaced. The dendrites were finer and less tapered. Cells in which we could identify an outer plexiform tree failed to cover the retina completely, but were nonrandomly distributed. We draw three main conclusions: (1) some nonmammalian vertebrates have separate inner and outer mosaics of large ganglion cells like those of mammals, (2) the vertical displacement of ganglion cell somata can vary widely within a single mosaic and may thus be functionally irrelevant, and (3) biplexiform ganglion cells exist in fish but differ in morphology from the biplexiform types described in some other vertebrates.
Animals↗
Correlated activity in the CNS: a role on every timescale?
Until recently, correlated neuronal activity was seen by many as an arcane subject, of interest only to those with mathematical minds and access to elaborate electronics. However, the list of situations in which correlated activity is known or strongly suspected to be highly influential now embraces almost every branch of neuroscience, including perception, memory and the development and plasticity of structural and functional linkages throughout the CNS. Previous reviews in TINS have covered several specific roles of correlated activity in detail. Here, my aim is to explore their diversity, emphasizing the organizing potential of correlation across timescales ranging from the momentary to the evolutionary.
Aging↗
Gross, microscopic and ultrastructural lesions of protoporphyria in Limousin calves.
The gross, microscopic and ultrastructural lesions associated with the genetic disease, protoporphyria, in Limousin cattle were studied in detail. The clinical signs and lesions were most severe in young animals. In the liver, the lesions consisted of portal fibroplasia, bile ductule hyperplasia, parenchymal cell swelling, and pigment accumulation. Maltese cross-like crystals were evident under polarized light. Ultrastructurally, there were large secondary lysosomes comprised of electron-dense granules associated with lipid droplets in hepatocytes. Phagocytic cells in the dermis also contained large heterogeneous secondary lysosomes.
Animals↗
Enhancing the laser scanning confocal microscopic visualization of Lucifer yellow filled cells in whole-mounted tissue.
The laser scanning confocal microscope (LSCM) is an extremely useful tool that allows fluorescently labelled cells to be visualized in whole-mount preparations. This is particularly advantageous, for example, in studying the dendritic trees of neurons with respect to their environment. One of the most popular, and easiest, ways to visualize a cell is to inject it intracellularly with the fluorophore Lucifer Yellow (LY). However, the argon gas lasers of most LSCM's are not well matched to the excitation spectrum of aqueous LY. When this largely inappropriate excitation is combined with standard filters, designed for fluorescein fluorescence rather than Lucifer Yellow, the resulting image is poor. We report that clearing LY-injected neurons in methyl salicylate and mounting them in Entellan, a non-aqueous medium of high refractive index, enhances their visualization on a Bio-Rad LSCM with standard fluorescein (FITC) filters to an unexpected degree. This technique also leads to a substantial reduction in photobleaching.
Animals↗
Changes in goldfish retinal ganglion cells during axonal regeneration.
Recent work suggests that mammalian retinal ganglion cells may become more like developing ganglion cells in form while regenerating through a peripheral nerve graft. We have injected Lucifer Yellow into regenerating ganglion cells of goldfish to look for similar changes. Within three weeks of injury, we saw dye-coupling to nearby cells, which is a common developmental feature in many species. Dendrites and axons, which in most mature ganglion cells are smooth, became varicose and hairy, like those examined in mammalian development. Secondary axons arose later, not only as side-branches of the primary axon but also from the soma, as in mammalian development and regeneration. Since, in fish, these responses are clearly an intrinsic part of functional regeneration, their equivalence in fish and mammals strengthens the view that a similar regenerative competence may exist in the retinal ganglion cells of all vertebrates.
Amidines↗
Morphological recovery of axotomized goldfish retinal ganglion cells in an environment known to prevent retinotopic refinement of their regenerated tectal arbors.
Axonal injury provokes well-characterized morphological changes in goldfish retinal ganglion cells. These reach a peak as the regenerating axons restore a grossly retinotopic projection map to the tectum, and then regress as the map is refined by a mechanism involving locally-correlated activity. The aim of this study was to look for any interdependence between morphological recovery and retinotopic refinement. Stroboscopic light was used to keep regenerated optic arbors in non-retinotopic locations for 70 days after optic nerve cut and lens ablation. Controls were kept in constant or diurnal light, both of which allow refinement of the retinotectal map. Nucleolar frequency, perikaryal area and nuclear area were used as indices of neuronal recovery, and ganglion cell counts were performed. After 35 days in diurnal light, the nucleoli of axotomized cells had increased in size, prominence and number, and both nucleus and cytoplasm had roughly doubled in area. After 70 days, these features had almost returned to normal not only in diurnal and constant light but in stroboscopic light as well. A small but significant cell loss, averaging 13.4-14.7%, was seen after optic nerve cut and lens ablation regardless of stage in regeneration (35 or 70 days) or lighting. Evidently, morphological recovery is independent of retinotopic refinement, which is known to be no further advanced after 70 days in stroboscopic light than after 35 days in diurnal light.
Animals↗
Professional practice committee: right on target.
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Humans↗
Ultrastructural changes in Brown Swiss cattle affected with bovine progressive degenerative myeloencephalopathy (Weaver syndrome).
Thirty Brown Swiss cattle, 7 to 30 months old, clinically affected with the weaver syndrome and five clinically normal Brown Swiss were studied. Ultrastructural examination mainly of the thoracic spinal cord revealed axonal changes accompanied by degeneration of myelin sheaths that were fragmented and lamellae vesiculated. The degeneration was accompanied by moderate gliosis and phagocytosis of degenerated myelin. There were no inflammatory changes. The ultrastructural changes may represent a disturbance of axoplasmic transport and subsequent axonal degeneration.
Animals↗
Topographic refinement of the goldfish retinotectal projection: sensitivity to stroboscopic light at different periods during optic nerve regeneration.
When the severed optic nerve of a goldfish regenerates, the restored retinotectal projection is at first only grossly topographic. Refinement occurs later, by a mechanism that is thought to depend on correlation in the electrical activity of neighbouring retinal ganglion cells because it can be blocked by exposure to tetrodotoxin or diffuse stroboscopic (strobe) light. To study the sensitivity of retinotectal map refinement to strobe light at different periods during regeneration, four equivalent groups of goldfish with severed right optic nerves and ablated right lenses were interchanged, at 21 day intervals, between strobe (S) and diurnal (D) light to generate four different exposure sequences. After 84 days, a localized iontophoretic injection of WGA-HRP was made into each left tectum to label retinal ganglion cells with terminal arbors at the injection site, and the degree of clustering of the labelled cells was estimated statistically to assess map refinement. Retinae exposed to the sequences SDDS, SSDD or DSSD were broadly similar to each other and to those seen previously after exposure for similar total periods to diurnal light, constant light or strobe light with the lens in place. However, those kept in diurnal light for the first 42 days and in strobe light thereafter (DDSS) revealed significantly less refinement, equivalent to that seen previously after just 42-44 days in diurnal light. Thus diffuse strobe light itself neither sharpens nor unsharpens the regenerated map: its immediate effect seems only to be the indefinite postponement of whatever refinement would otherwise have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Divergent axon collaterals in the regenerating goldfish optic tract: a fluorescence double-label study.
In the normal goldfish, optic axons are distributed between the two arms (brachia) of each optic tract, in such a way that each axon enters the tectum close to its retinotopic termination site. We have shown previously that regenerating axons at first express little or no preference for their normal brachium. Later, however, a partial refinement of the brachial pathway takes place, implying that some axons must have sent out divergent collateral branches and then eliminated the least appropriate. We have now studied the formation and subsequent loss of axon collaterals in regeneration using retrogradely transported fluorescent dyes. We labelled the axons in the medial brachium with Fast Blue and those in the lateral brachium with Diamidino Yellow in a way that avoided cross-contamination. In normal fish, yellow-labelled ganglion cells dominated the dorsal retina and blue-labelled ganglion cells the ventral, with only a narrow zone of overlap. Double-labelled cells were not found. In fish labelled early in regeneration, however, both dyes were spread over the entire retina in single- and double-labelled ganglion cells. As regeneration progressed, each dye again came to dominate its appropriate retinal region; but much less strongly, confirming previous results. At the same time, double-labelled cells became harder to find. From 60 days after nerve cut onwards they were rare, and largely confined to the boundary zone between dorsal and ventral retina.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Retinotopic refinement of the regenerating goldfish optic tract is not linked to activity-dependent refinement of the retinotectal map.
The cut optic nerve of a goldfish can regenerate, restoring an orderly projection from the retina to the optic tectum. At first, regenerating axons make transient connections, many of them in inappropriate tectal locations. Later, their arrangement is gradually refined into an accurate retinotectal map by a process that depends on afferent activity. On their way to the tectum, many regenerating axons make erroneous choices between the two arms (brachia) of the optic tract. However, since they commonly possess divergent collateral branches, a secondary refinement of the brachial pattern can occur by selective collateral elimination. How or why a particular collateral is lost is not known, but we have previously suggested that sibling branches might compete to form stable tectal synapses, implying that there might be a causal link between refinement of the brachial pattern and refinement of the retinotectal map. In this paper, we have tested directly for such a link, blocking map refinement with tetrodotoxin (TTX) or stroboscopic light, verifying the effectiveness of the block and measuring the extent of brachial refinement by standard methods in experimental and control fish. Both TTX and stroboscopic light reliably prevented map refinement, their results being indistinguishable. However, neither had even the slightest detrimental effect on brachial refinement, either 42 days or 70 days after nerve cut. Evidently, neither activity nor a sharp retinotectal projection is necessary for brachial refinement. Theory and experiment both dictate that the basic projection pattern be controlled by a mechanism (such as chemoaffinity) that is independent of activity, and it would seem that selective collateral loss must depend on the same mechanism.
Animals↗
Comments on 'A proposal for a generally applicable de minimis dose'.
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Humans↗
A sharp retinal image increases the topographic precision of the goldfish retinotectal projection during optic nerve regeneration in stroboscopic light.
Locally-correlated neural activity appears to play a key role in refining topographically mapped projections. The retinotectal projection of the goldfish normally regains a high degree of spatial precision after regeneration of a cut optic nerve, but it fails to do so if retinal ganglion cell activity is blocked by tetrodotoxin, or if local correlations in activity are masked by the synchronizing effect of stroboscopic light. A sharp retinal image is not normally needed for a sharp map because local correlation occurs even in darkness or diffuse light, but the possibility that a sharp image might restore local correlation and sharpen the map in stroboscopic light, though taken into account in earlier experiments, has not previously been tested. The precision of the retinotectal map was therefore studied, by retrograde transport of WGA-HRP from a standard tectal injection site and quantitative analysis of the labelled ganglion cell distribution, after regeneration of a cut optic nerve for 83-84 days in either continuous stroboscopic light or normal diurnal light. The lens of the eye was either ablated to blur the retinal image or sham-operated. Two different strobe flash patterns used in previous experiments were also compared. With the lens ablated, stroboscopic light impaired map refinement significantly, confirming previous results. A rapid, irregular flash pattern averaging about 5 Hz was rather more effective than a regular 1 Hz pattern. With the lens intact, however, neither pattern had any detectable effect. The significant gain in precision resulting from a sharp retinal image in these circumstances suggests that common mechanisms could underlie both the internal refinement of the retinotectal map and such directly experience-sensitive processes as the experimental realignment of binocular maps in the frog Xenopus, and of auditory and visual maps in the barn owl.
Animals↗
Topographic refinement of the regenerating retinotectal projection of the goldfish in standard laboratory conditions: a quantitative WGA-HRP study.
The topographic precision of the regenerating retinotectal projection of the goldfish was studied between 18 and 524 days (at 20 degrees C) after optic nerve cut, using retrograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA-HRP) from one of two standardized tectal injection sites. All labelled ganglion cells in each flat-mounted retina were plotted individually, and their degree of dispersion was assessed by a statistical method based on distance to nearest neighbour. Labelled cells in normal fish were clustered tightly, covering on average only 1.3% of the retina. Early in regeneration (18-28 days) they were widely dispersed, covering up to 75.2%, and they did not begin to form recognizable clusters at appropriate sites until about 35 days after nerve cut. Between 18 and 70 days, the proportion of retina covered by labelled cells fell dramatically, halving about every 14 days. Between 70 and 524 days, no further reduction could be demonstrated: overall, clusters remained significantly larger than normal, though a few individual retinae were virtually normal. Several others, labelled from similar single injections between 56 and 524 days after nerve cut, showed pairs of cell clusters; a sign that persistent errors in topography are common. The very wide initial scatter of labelled cells reflects a striking lack of 'goal-directedness' in regenerative axon growth. Extensive branching in the optic nerve, tract and tectum, for which there is already evidence, must contribute to this. Though uptake of some WGA-HRP by nonsynaptic growth cones cannot be ruled out, other evidence for mislocated functional synapses at early stages encourages us to favour 'trial and error' synapse formation as the likely basis of map refinement.
Animals↗