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G W Balkema

Publications and source records attributed to G W Balkema.

14 recordsLinked to original sources
PubMed1992

Biochemical correlates of epilepsy in the E1 mouse: analysis of glial fibrillary acidic protein and gangliosides.

The E1 (epileptic) mouse is considered a model for complex partial seizures in humans. Seizures in E1 mice begin around 7-8 weeks of age and persist throughout life. To determine if astrocytic gliosis was present in adult seizing E1 mice, the distribution of glial fibrillary acidic protein (GFAP) was studied in the hippocampus using an antibody to GFAP. The mean number of GFAP-positive cells per square millimeter of hippocampus was approximately 15- to 40-fold higher in adult E1 mice than in nonseizing control C57BL/6J (B6) mice or in young nonseizing E1 mice. Relative GFAP concentration (expressed per milligram of total tissue protein) in hippocampus and cerebellum was estimated by densitometric scanning of peroxidase-stained western blots. GFAP concentration was 2.7-fold greater in hippocampus of adult seizing E1 mice than in the control B6 mice. No differences in GFAP content were detected between the strains in the cerebellum. Because gangliosides can serve as cell surface markers for changes in neuronal cytoarchitecture, they were analyzed to determine if the gliotic response in E1 mice was associated with changes in neural composition. Although the total ganglioside concentration of hippocampus, cerebral cortex, and cerebellum was similar in adult E1 and control B6 mice, a synaptic membrane enriched ganglioside, GD1a, was elevated in the adult E1 cerebral cortex and hippocampus. The findings indicate that E1 mice express a type of gliosis that is not accompanied by obvious neuronal loss.

Animals↗
PubMed1991

A synaptic antigen (B16) is localized in retinal synaptic ribbons.

This morphological and biochemical study examines the cytoplasmic synaptic determinant recognized by a monoclonal antibody (B16). This antibody was generated by using an immunosuppression protocol that generates antibodies to relatively rare antigens. The B16 antibody labels structures in the brain that are dot-shaped and in the retina that resemble synaptic ribbons in their location, size, developmental emergence, and biochemical composition. The antigen is apparently conserved across species as it is found in retinas from lizards, frogs, fish, birds, mice, rats, rabbits, cats, and monkeys. This paper focuses on observations in the murine retina. Labeling in the outer plexiform layer of the retina is confined to the margin between the outer plexiform layer (OPL) and the outer nuclear layer. The labeled structure resembles a semiellipse or an arc with the open end facing the OPL and the top facing the outer nuclear layer. Overall, the arc is approximately 1 micron in length and less than 0.5 micron thick. Approximately 10% of the labeled arcs occur in a proximal stratum of the OPL and form a planar cluster that resembles a flat plaque parallel to the OPL. Five to ten arcs are found in each plaque. The arcs found within the plaques are approximately 50% smaller than the larger isolated arcs. Counterstaining with peanut agglutinin (PNA), a lectin that recognizes cone photoreceptors and their associated processes, demonstrates that the plaques are associated with the cone pedicles. Animals that have a higher ratio of cones/rods than mice demonstrate a much higher ratio of plaques/isolated arcs in the OPL. The structure labeled in the inner plexiform layer resembles a short bar (0.8 micron long by less than 0.5 micron wide) that is confined to the inner half of the inner plexiform layer in mice. The relative mobility (Mr) of the B16 antigen obtained from mouse retinal and brain tissue is 88 kD, as determined by SDS-PAGE followed by Western blotting. The mouse 88 kD protein is relatively soluble (precipitates at 70% ammonium sulphate) and elutes at a pH of 7.3 from an isoelectric focusing column. It appears that the determinant recognized by the B16 antibody is a previously undescribed synaptic protein that is associated with the synaptic ribbons in photoreceptor and bipolar terminals of most vertebrate retinas.

Ambystoma↗
PubMed1991

Impaired visual thresholds in hypopigmented animals.

Ocular hypopigmentation is associated with neurological defects in structure and function. This paper investigates the absolute visual thresholds in dark-adapted hypopigmented animals compared to their normally pigmented controls. Here we asked (1) whether the threshold elevation found in hypopigmented animals is a general consequence of the reduction in melanin content; (2) if so, which melanin components in the eye are likely to influence visual thresholds; and (3) whether similar threshold defects can be detected in orders other than rodents. By single-unit recordings from the superior colliculus, we compared incremental thresholds of normal black mice of the C57BL/6J strain to hypopigmented mutants: beige (bg/bg), pale ear (ep/ep), and albino (c2J/c2J) mice, three mutants in which melanin pigment throughout the body is affected; and Steel (Sl/Sld) and dominant-spotting/W-mice (W/Wv), two mutants with normal pigmentation in the retinal pigment epithelium (RPE) but without any melanin in the choroid or the rest of the body. We found that all mutants had elevated thresholds that varied with the reduction in melanin. The albinos were 25 times less sensitive than black mice, pale ear mice 20 times, beige mice 11 times, and Steel and W-mice 5 times. The mean thresholds of dark-adapted black mice were 0.008 cd/m2. Recordings from rabbits showed a similar impairment of visual sensitivity; incremental thresholds were elevated 40 times in New Zealand-White albino rabbits (0.0008 cd/m2) compared to Dutch-Belted pigmented controls (0.00002 cd/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Albinism, Ocular↗
PubMed1990

Origins of uncrossed retinofugal projections in normal and hypopigmented mice.

In albinos, the retinofugal projections to the ipsilateral side of the brain are reduced (e.g., see Guillery, 1969; La Vail et al., 1978; Lund, 1965). Although all ganglion cell types are affected, in mice the displaced ganglion cell population is the main target of the albino mutation (Dräger & Olsen, 1980). Here we tested whether this preferential effect on displaced ganglion cells is a general consequence of the melanin reduction or a pleiotropic effect unique to the albino locus, by retrogradely tracing retinal ganglion cells in normal C57BL/6J mice and in several non-allelic hypopigmentation mutants on the same background: albino (C57BL/6J-c2J), beige (C57BL/6J-bg), pale ear (C57BL/6J-ep), ruby-eye/haze (C57BL/6J-ru-2hz), and pearl (C57BL/6J-pe). All mutants have lower overall cell counts in the ipsilateral projection, but the displaced population is disproportionately affected: the albinos contain 42% of the normal number of displaced ganglion cells, and the other mutants have an average 57% of normal counts. The reduction in uncrossed retinofugal projections in albinos affects the inputs to the lateral geniculate nucleus and the superior colliculus, but not to the suprachiasmatic nucleus (Dräger, 1974). To address the question in which way the susceptible uncrossed projections differ from the nonsusceptible one, we compared ganglion cells backfilled from the suprachiasmatic nucleus to ganglion cells backfilled from the optic tract at geniculate level. Whereas the uncrossed optic tract projection originates from the binocular region in the ventro-temporal retina and contains a high fraction of large and displaced ganglion cells (Dräger & Olsen, 1980), both the crossed and uncrossed inputs to the suprachiasmatic nucleus originate from the entire retina with a relative preference for the lower nasal region that corresponds to part of the monocular visual field; all ganglion cells projecting to the suprachiasmatic nucleus are of medium size, and they are located in the ganglion cell layer. These observations allow the following conclusions: (1) All genetic mutants which cause a reduction in ocular melanin, regardless of the molecular or cell-biological mechanism underlying the pigment reduction, result in decreased uncrossed projections; this confirms previous reports (La Vail et al., 1978, Sanderson et al., 1974). (2) The decrease affects only projections involved in binocular vision. (3) In mice, the ganglion cells displaced to the inner nuclear layer, and hence located closer to the retinal pigment epithelium, are disproportionately affected by the melanin reductions. These observations may provide cues to the spatio-temporal mechanism of the

Afferent Pathways↗
PubMed1988

Elevated dark-adapted thresholds in albino rodents.

Albino mice and rats have elevated dark-adapted thresholds compared to normally pigmented animals. The absolute dark-adapted incremental threshold for black mice is about 1.5 log units lower than the threshold for albino mice when measured by single-unit recordings from the superior colliculus. Cell counts from the outer nuclear layer in albino mice are not significantly different from those in black mice, indicating that the elevated dark-adapted thresholds are not due to light damage of photoreceptor cells. No photoreceptor outer segment damage was found in these albino animals at the light or electron microscopic level. These experiments have been repeated in hooded and albino rats. The thresholds from albino rats were about 2 log units higher than the thresholds from pigmented rats in the dark-adapted state. The proximity of the retinal pigment epithelium (RPE) and the pigmented choroid to the photoreceptors in these animals suggests that a reduction in ocular melanin in hypopigmented animals may be causal to their elevated thresholds.

Albinism↗
PubMed1984

Visually evoked eye movements in mouse mutants and inbred strains. A screening report.

The authors screened various inbred strains and mutants of the mouse, Mus musculus, for qualitatively abnormal or reduced numbers of optokinetic nystagmus (OKN) eye movements. Thirteen hypopigmentation mutants and ten neuromuscular mutants were found to have abnormal or markedly reduced OKN, but none of these mutants had retinal degeneration. Ten other hypopigmentation mutants and nine other neuromuscular mutants had relatively normal OKN, thus showing that neither hypopigmentation nor neuromuscular abnormality per se are well-correlated with abnormal OKN. These findings show that many mutants with visual defects are available from existing holdings. These visual mutants may serve as a resource for the study of the function and development of the mammalian visual system.

Animals↗
PubMed1983

Discrete visual defects in pearl mutant mice.

The mutant mouse pearl, characterized by its hypopigmentation, has a specific functional defect in a sensory system--the retina. The intact pearl mouse has reduced sensitivity in the dark-adapted condition. Normal sensitivity is restored by isolation and superfusion of the retina with bicarbonate-buffered Ringer solution, suggesting that the retinal expression of the pearl mutation depends on a diffusible substance. The pearl phenotype is described as a possible model for human congenital stationary night blindness.

Animals↗
PubMed1982

Electrophysiology of retinal ganglion cells in the mouse: a study of a normally pigmented mouse and a congenic hypopigmentation mutant, pearl.

1. The organization of the receptive fields of retinal ganglion cells in te normal mouse was studied qualitatively in recordings from 43 single axons in the optic nerve and optic tract, and the light sensitivity was studied quantitatively in 26 of these cells by measuring incremental sensitivity. 2. The receptive fields of normal animals were elliptical, had concentric center and peripheral subdivisions, and had an antagonistic center/surround organization; the receptive-field centers ranged from 1.95 to 83 degrees in diameter, with a median of 7 degrees. 3. The incremental sensitivity to white light was measured using a criterion response of 10 extra spikes; the most sensitive dark-adapted cell required a stimulus luminance of 3.5 x 10(-3) cd/m2 to generate a criterion response. 4. The action spectrum measured at seven different wavelengths (433-619 nm) from ganglion cells in the normally pigmented mouse resembled the CIE (International Commission on Illumination, CIE 1957 (11)) relative scotopic luminous efficiency function (41) and is consistent with a curve having a peak around 500 nm. 5. On light adaptation with blue light (less than 460 nm), the sensitivity to longer wavelength stimuli increased by 0.2-0.5 log units relative to the sensitivity to the shorter wavelengths; these results are compatible with the presence of a photoreceptor sensitive to long wavelengths in the normally pigmented mouse (C57BL/6J+/+). 6. The organization of the receptive fields of 48 retinal ganglion cells from the hypopigmentation mutant pearl (C57BL/6J-pe) was also studied qualitatively; the receptive field organization was similar to that of the normally pigmented mouse. 7. In 25 cells from dark-adapted pearl mice, the incremental sensitivity to white light was, on the average, 1.6 log units less than that for normal mice. 8. The dark-adapted action spectrum of pearl mice was similar to that of normally pigmented mice. However, a shift in sensitivity to longer wavelengths did not occur on selective light adaptation with the most luminous blue light (less than 460 nm) background that we could produce. 9. We conclude that pearl is one of the mammalian genes that codes for functions that affect dark-adapted retinal sensitivity. The results of this study and past studies suggest that the pearl gene's action on light sensitivity is predominantly within the retina and before (distal to) the ganglion cells.

Adaptation, Physiological↗
PubMed1982

Cone outer segment shedding in the goldfish retina characterized with the 3H-fucose technique.

After an intravitreal injection of 3H-fucose, red- and blue-sensitive cone outer segments (OSs) in the goldfish retina became heavily labeled, green-sensitive cone OSs showed light labeling, and rod OSs showed virtually no labeling. Fish were maintained in white light (light/dark: 12 hr/12 hr; 6 to 10 weeks) and were injected with 3H-fucose 24 hr before sacrifice. After light onset, only phagosomes with no label were found in the retinal pigment epithelium (RPE); after light offset, phagosomes with heavy, light, or no label were found in the RPE. A broad peak of cone OS shedding derived from all cone types was found beginning 2 hr after light offset and returning to baseline levels after 12 hr, with a maximum at 4 to 6 hr. When the white light was replaced with red light during the final 24 hr (irradiance matched to the white light at 625 nm), the green cones showed a reduction in shedding by 62%, the rods showed a 48% reduction in shedding, and the number of heavily labeled phagosomes was reduced by 24% (a value that may reflect normal and red cone shedding and a reduction in blue cone shedding). The results suggest that chromatic stimulation during the light period may influence the shedding response of a given class of cone OS. Finally, the 3H-fucose technique is useful for determination of the photoreceptor OS from which a given phagosome in the RPE originates in this species.

Animals↗
PubMed1981

Retrograde labeling and dissociation of mouse retinal ganglion cells.

Mouse retinal ganglion cells were labeled by retrograde axonal transport of the fluorescent dyes, DAPI and Primulin. The labeled retinae were dispersed by papain treatment and mechanical dissociation. Among the cells in the suspension, the ganglion cells could be unequivocally identified by their intense DAPI/Primulin fluorescence. These results establish that it is possible to label specific neurons in the central nervous system by retrograde transport of fluorescent dyes and to identify the labeled cells after proteolytic dissociation.

Amidines↗
PubMed1981

Characterization of abnormalities in the visual system of the mutant mouse pearl.

Mice of the mutant strain pearl (pe/pe) differ from the wild strain by a single gene mutation, which leads to a lightening of the coat color. We tested this strain to see if this mutant gene also expressed itself in one or more visual abnormalities. Pearl mice were found to lack totally the optokinetic nystagmus reflex that was present in every normal mouse that we examined. This lack of optokinetic nystagmus was not due to oculomotor defects, since postrotatory nystagmus was normal. As described for other pigmentation mutants, we found that pearl mutants had a reduced ipsilateral projection to the lateral geniculate nucleus, superior colliculus, and visual cortex. We recorded from single cells in the superior colliculus and found response properties and light sensitivities to be normal over the luminance range at which optokinetic nystagmus was tested. However, at very dim backgrounds (scotopic levels), the incremental sensitivities of these cells in pearl mice were about 100 times lower than those of normal mice. This reduction in sensitivity was restricted to scotopic backgrounds and was not due to abnormalities in either the time course of dark adaptation or the receptive field sizes of single cells. In recordings of the electroretinographic response, both the waveforms and the normalized magnitudes of the A and B waves of pearl were indistinguishable from those of normal mice, which seems to indicate that the cause of pearl's sensitivity defect is located central to the main electrical events in the photoreceptors. The normality of many aspects of the visual system of pearl mice contrasts sharply with the complete absence of optokinetic nystagmus, with the reduced ipsilateral projection, and with the reduced dark sensitivity of the cells in the superior colliculus.

Animals↗
PubMedDate not supplied

Light-dependent antibody labelling of photoreceptors.

Monoclonal antibodies are tools widely used to analyse the structure of the nervous system. Whereas some labelling patterns are highly reproducible, others appear to vary from one preparation to the next, as we noticed in particular for some antibodies with respect to photoreceptor labelling. To establish whether some of this variability can be linked to functional criteria, we tested for light-dependence. We found two antibodies that label photoreceptor outer segments, only when the retina has been illuminated, and a third antibody that has a selective affinity for dark-adapted outer segments. The two antibodies against light-activated sites are primarily directed against the highly phosphorylated neurofilament subunit at relative molecular mass 200,000 (200K). One of them, RT97, recognizes on immunoblots, in addition to neurofilaments, a light-activated epitope on a protein that resembles the photopigment rhodopsin, presumably a phosphorylation-dependent site. Antibodies like those described here may allow the study of physiological processes such as light and dark adaptation using morphological techniques.

Adaptation, Ocular↗