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M S Silverman

Publications and source records attributed to M S Silverman.

At least 37 records · Page 2Linked to original sources

Photoreceptor transplantation in inherited and environmentally induced retinal degeneration: anatomy, immunohistochemistry and function.

In conclusion, we have shown that photoreceptors can be transplanted to retina in which the host's photoreceptors are lost by environmental (constant light) or inherited deficits. Furthermore transplanted photoreceptor cells maintain basic characteristics of normal photoreceptor cells by producing opsin and maintaining an intercellular organization and apposition to the host retina that is similar to that seen in the normal outer nuclear layer. To accomplish this we have devised a method to isolate the intact photoreceptor layer. This is significant because it will be necessary to maintain tight matrix organization if coherent vision is to be restored to the retina compromised by the loss of photoreceptors. We have further developed a surgical approach which minimizes trauma to the eye and allows controlled positioning of sheets of transplanted photoreceptors to their homotopic location within the eye. In addition these methods for transplantation and isolation of photoreceptors could be utilized to prepare and transplant other retinal layers so that selected populations of retinal cells can be used in other neurobiological investigations. Photoreceptors can be transplanted when developing or when mature. Not only can mature rat photoreceptors can be transplanted, but we have shown that mature photoreceptors from human donors can be transplanted as well. This is significantly different from neurons which must be immature in order to be transplanted. At present the reason for this difference is not known but has obvious importance for retinal and neural transplantation research in general. Finally, we have shown that transplanted photoreceptors activate the host's dystrophic retina in a light dependent manner that closely resembles the activation pattern seen in normal retina. This finding taken together with our results showing that human photoreceptors can be transplanted presents the possibility that some forms of human blindness might eventually be ameliorated by photoreceptor transplantation. The authors are grateful to A. I. Cohen, and N. W. Daw for helpful discussions; to C. Barnstable for gifts of antibody; and to J. Lett for excellent technical assistance. This work was supported by grants from NIH, National Retinitis Pigmentosa Foundation, the Monsanto Company; and an Alfred P. Sloan Fellowship to MSS.

Age Factors↗

Functional anatomy of macaque striate cortex. I. Ocular dominance, binocular interactions, and baseline conditions.

A series of experiments was carried out using 14C-2-deoxy-d-glucose (DG) in order to examine the functional architecture of macaque striate (primary visual) cortex. This paper describes the results of experiments on uptake during various baseline (or reference) conditions of visual stimulation (described below), and on differences in the functional architecture following monocular versus binocular viewing conditions. In binocular "baseline" experiments, monkeys were stimulated either (1) in the dark, (2) with a diffuse gray screen, or (3) with a very general visual stimulus composed of gratings of varied orientation and spatial frequency. In all of these conditions, DG uptake was found to be topographically uniform within all layers of parafoveal striate cortex. In monocular experiments that were otherwise similar, uptake was topographically uniform within the full extent of the eye dominance strip, in all layers. Certain other visual stimuli produce high uptake in the blobs, and still another set of visual stimuli (including high-spatial-frequency gratings) produce highest uptake between the blobs at parafoveal eccentricities, even in an unanesthetized, unparalyzed monkey. Eye movements per se had no obvious effect on striate DG uptake. Endogenous uptake in the blobs (relative to that in the interblobs) appears higher in the squirrel monkey than in the macaque. The pattern of DG uptake produced by binocular viewing was found to deviate in a number of ways from that expected by linearly summing the component monocular DG patterns. One of the most interesting deviations was an enhancement of the representation of visual field borders between stimuli differing from each other in texture, orientation, direction, etc. This "border enhancement" was confined to striate layers 1-3 (not appearing in any of the striate input layers), and it only appeared following binocular, but not monocular, viewing conditions. The border enhancement may be related to a suppression of DG uptake that occurs during binocular viewing conditions in layers 2 + 3 (and perhaps layers 1 and 4B), but not in layers 4Ca, 4Cb, 5 or 6. Another major class of binocular interaction was a spread of neural activity into the "unstimulated" ocular dominance strips following monocular stimulation. Such an effect was prominent in striate layer 4Ca, but it did not occur in layer 4Cb. This "binocular" spread of DG uptake into the inappropriate eye dominance strip in 4Ca may be related to the appearance of orientation tuning and orientation columns in that layer. No DG effects were seen that depended on the absolute disparity of visual stimuli in macaque striate cortex.

Animals↗

Functional anatomy of macaque striate cortex. II. Retinotopic organization.

Macaque monkeys were shown retinotopically-specific visual stimuli during 14C-2-deoxy-d-glucose (DG) infusion in a study of the retinotopic organization of primary visual cortex (V1). In the central half of V1, the cortical magnification was found to be greater along the vertical than along the horizontal meridian, and overall magnification factors appeared to be scaled proportionate to brain size across different species. The cortical magnification factor (CMF) was found to reach a maximum of about 15 mm/deg at the representation of the fovea, at a point of acute curvature in the V1-V2 border. We find neither a duplication nor an overrepresentation of the vertical meridian. The magnification factor did not appear to be doubled in a direction perpendicular to the ocular dominance strips; it may not be increased at all. The DG borders in parvorecipient layer 4Cb were found to be as sharp as 140 micron (half-amplitude, half width), corresponding to a visual angle of less than 2' of arc at the eccentricity measured. In other layers (including magnorecipient layer 4Ca), the retinotopic borders are broader. The retinotopic spread of activity is greater when produced by a low-spatial-frequency grating than when produced by a high-spatial-frequency grating. Orientation-specific stimuli produced a pattern of activation that spread further than 1 mm across cortex in some layers. Some DG evidence suggests that the spread of functional activity is greater near the foveal representation than near 5 degrees eccentricity.

Animals↗

Functional anatomy of macaque striate cortex. III. Color.

Using spatially diffuse stimuli (or sinusoidal gratings of very low spatial frequency), levels of 14C-2-deoxy-d-glucose (DG) uptake produced by color-varying stimuli are much greater than those produced by luminance-varying stimuli in macaque striate cortex. Such a difference in DG results is consistent with previous psychophysical and electrophysiological results from man and monkey. In DG experiments with color-varying gratings of low and middle spatial frequencies, or with spatially diffuse color variations, DG uptake was highest in the cytochrome oxidase blobs, as was also seen with low-spatial-frequency luminance gratings. High-spatial-frequency, color-varying uptake patterns were shifted to cover both blob and interblob regions in a manner similar to that of the patterns obtained with middle-spatial-frequency luminance stimuli. However, in no instance did chromatic gratings produce uptake restricted to the interblob regions, as with the pattern seen with the highest-spatial-frequency luminance gratings. Thus, DG uptake is relatively higher in the interblob regions when comparing luminance with color-varying gratings that are otherwise similar. It was also possible to show DG evidence for receptive-field double-opponency in the upper-layer blobs, but color sensitivity in layer 4Cb appears single-opponent. The DG results suggest that color sensitivity is also high in the lower-layer (layers 5 + 6) blobs, and that many layer 5 receptive fields are double-opponent. Striate layers 4Ca and 4B-appeared color-insensitive in a wide variety of DG tests; this supports the idea of a color-insensitive stream running from the magnocellular LGN layers through striate layers 4Ca and 4B to extrastriate areas MT and V3. There was also a major effect due to wavelength: long and short wavelengths produced much more uptake than did middle wavelengths, even when all colors were equated for luminance and saturation. No variation with eccentricity was seen in cortical color sensitivity, at least between 0 degrees and 10 degrees.

Animals↗

Functional anatomy of macaque striate cortex. V. Spatial frequency.

When macaque monkeys view achromatic, sinusoidal gratings of a single spatial frequency, the pattern of 14C-2-deoxy-d-glucose (DG) uptake produced by the gratings is shown to depend on the spatial frequency chosen. When a relatively high (5-7 cycles/deg) spatial frequency is shown binocularly at systematically varied orientations, uptake in parafoveal striate cortex is highest between the cytochrome oxidase blobs (that is, in the interblobs) in layers 1, 2, and 3. In layers 4B, 5, and 6, where the cytochrome oxidase blobs are faint or absent, DG uptake is highest in a periodic pattern that lies in register with the interblobs of layers 2 + 3. When the grating is, instead, of relatively low (1-1.5 cycles/deg) spatial frequency, DG uptake is highest in the blobs, in the blob-aligned portions of layers 1-4B, and in the lower-layer blobs as well. These variations in DG topography are confirmed in stimulus comparisons within a single hemisphere. Presumably, this shift in functional topography within the extra-granular layer is the primate homolog of "spatial frequency columns" shown earlier in the cat (Tootell et al., 1981; Silverman, 1984). In the well-differentiated architecture of primate striate cortex, laminar differences produced by high- versus low-spatial-frequency gratings are visible as well. Gratings of very high spatial frequency produce much higher uptake in 4Cb (which receives input from the parvocellular LGN layers) than in 4Ca (which gets its input from the magnocellular LGN layers). Gratings of low spatial frequency produce the converse result. Presumably, cells in the magnocellular LGN layers and/or in the magnocellular-dominated layer 4Ca have lower average spatial frequency tuning (larger receptive fields) than their counterparts in the parvocellular LGN and/or in striate layer 4Cb. The DG patterns produced by various spatial frequencies also vary with eccentricity, in a manner consistent with known, eccentricity-dependent variations of receptive-field size and spatial frequency tuning. Thus, gratings of a "middle"-spatial-frequency range (4-5 cycles/deg) produce high uptake in the blobs near the foveal representation and high uptake in the interblobs at more peripheral eccentricities, including 5 degrees. This shift in DG topography also includes the transition zone near 3 degrees, where the level of stimulus-driven uptake is as high in the blob regions as it is in interblob regions. Variations in uptake between layers 4Ca and 4Cb, as a function of eccentricity, shift in parallel with the changes in the upper-layer topography.

Animals↗

Modified technique for cytochrome oxidase histochemistry: increased staining intensity and compatibility with 2-deoxyglucose autoradiography.

Staining the brain for cytochrome oxidase (CO) produces patterns which can resemble the patterns produced by 2-deoxyglucose (2-DG) autoradiography. In order to assess the differences between CO patterns of long-term metabolic activity and 2-DG patterns of short-term activity, comparisons should, ideally, be made on the same section. Consequently, we have made certain modifications in the standard CO histologic procedure which improve the stain and allow both 2-DG autoradiography and CO staining on the same section.

Animals↗

Penile prosthetics: characteristics of veteran patients and their spouses.

This study examined the characteristics of couples in whom the male partner was experiencing erectile difficulties and seeking treatment by surgical intervention with the penile prosthesis. The purpose was to examine and describe the psychological characteristics of the individual spouses as well as the nature of their relationship. Additional purposes were to develop an ongoing assessment program and establish normative data on this particular population. Twelve couples in whom the men were considered by their physicians as potential candidates for the penile prosthesis were the subjects. The Minnesota Multiphasic Inventory, the Marital Communication Inventory, and the Multi-Modal Marital Satisfaction Questionnaire were administered to husband and wife. The couples' communication scores were lower than expected from established norms. The scores on the Marital Satisfaction Inventory, however, indicate relatively high levels of satisfaction with the marriage overall. A high positive correlation was found between the measures of communication and marital satisfaction. The MMPI data indicate that there is no one profile configuration that is characteristic of either husbands or wives. As a group, neither the husbands nor the wives evidence any signs of psychopathology. A composite description of the couples is presented along with a description of the individual psychological characteristics of the husbands and wives as a group. The findings are discussed in terms of their implications for treatment, and recommendations for further research are indicated.

Aged↗

Picture processing techniques applied to autoradiographic studies of visual cortex.

Picture processing techniques are applied to 2-deoxyglucose autoradiographs of sections from striate cortex and to patterns resulting from staining these sections for cytochrome oxidase. This procedure allows computer identification of deoxyglucose active and inactive regions in the autoradiographs and cytochrome active and inactive regions in the stain patterns. Subsequently, the topographical relationship between these patterns can be quantitatively analyzed by means of overlap and density distribution measures and can be displayed using color enhanced graphics. The processing techniques have been applied in studies of the functional organization of visual cortex in primates. Computer graphic techniques have allowed implementation of split-field presentations of stimuli in deoxyglucose experiments. An application of this split-field technique for presenting multiple-stimuli to distinct parts of the visual field is described and an autoradiograph from a split-field experiment is shown.

Animals↗

Topography of cytochrome oxidase activity in owl monkey cortex.

In primate cortical tissue which has been stained for the mitochondrial enzyme cytochrome oxidase, a topographical pattern of regularly spaced blobs has been demonstrated in primary visual cortex (Hendrickson, A. E., S. P. Hunt, and J. -Y. Wu (1981) Nature 292: 605-607; Horton, J. C., and D. H. Hubel (1981) Nature 292: 762-764), and a pattern of stripes has been shown in secondary visual cortex (V2) as well (Livingstone, M. S., and D. H. Hubel (1982) Proc. Natl. Acad. Sci. U. S. A. 79: 6098-6101; Tootell, R. B. H., M. S. Silverman, E. Switkes, and R. L. De Valois (1982) Soc. Neurosci. Abstr. 8: 707). These regular cytoarchitectonic landmarks have proven extremely useful in parsing the functional and anatomical architecture of these two cortical areas. In order to look for similar landmarks in other cortical areas of a primate, we completely unfolded the cortical gray matter in the owl monkey (Aotus trivirgatus), sectioned it parallel with the flattened cortical surface, and stained the tissue for cytochrome oxidase. Distinctive cytochrome oxidase topographies were found in about seven different cortical areas. As in other primates, area V1 is characterized by blobs and area V2 is characterized by strips. In the owl monkey, area MT is characterized by an elaborate topography of dark staining in layers 1 to 4, interspersed with light blob-shaped regions, and partially surrounded by a dark ring. Many of these topographic inhomogeneities are also reflected in the lower layer myelination topography in MT. Visual area(s) VP/VA is characterized by an irregular or strip-like topography. In some animals, a distinctive topography can be seen in area DX, which is presumably equivalent to either area DM or DI. Primary auditory cortex stains very darkly, but the overall shape of area A is quite variable and the borders are indistinct. Somatosensory area 3B stains quite darkly with sharp borders, but again the overall shape of area 3B is different from that previously described.

Animals↗

A model framework of alcoholism counseling: cyclic process of intensification, paradoxical shifting, and differentiation.

While recent literature on individual and family therapy has increasingly focused on the nature and use of paradoxical styles of intervention, little has been published concerning the use of paradox in alcoholism counseling. Alcoholism represents a type of problem that can lend itself to the use of such interventions. This paper first reviews the nature of paradoxical styles of intervention in relation to alcoholism. It then presents three developmentally determined paradoxical dynamics: intensification, paradoxical shifting, and differentiation. These are defined and examples from case studies are given for each. Therapists working with alcoholics are encouraged to consider the use of these patterns of response with their clients.

Alcoholism↗

Functional organization of the second cortical visual area in primates.

The functional organization of the second cortical visual area was examined with three different anatomical markers: 2-[14C]deoxy-D-glucose, cytochrome oxidase, and various myelin stains. All three markers revealed strips running throughout the area, parallel to the cortical surface. The boundaries of these strips provide an anatomical criterion for defining the borders of this extrastriate region. Further, the demonstration of these strips allows a functional and anatomical analysis of modules in the area, just as the recent demonstration of spots in the primary visual cortex has allowed an analysis of modules there. The strips differ structurally and functionally from interstrip regions and these differences are similar to those seen between the spots and the interspot regions in the primary visual cortex. In the macaque the strips and spots differ with regard to binocular organization.

Animals↗

Deoxyglucose analysis of retinotopic organization in primate striate cortex.

We have anatomically analyzed retinotopic organization using the 14C-labeled 2-deoxy-D-glucose method. The method has several advantages over conventional electrophysiological mapping techniques. In the striate cortex, the anatomical substrate for retinotopic organization is surprisingly well ordered, and there seems to be a systematic relationship between ocular dominance strips and cortical magnification. The 2-deoxyglucose maps in this area appear to be largely uninfluenced by known differences in long-term metabolic activity. This method should prove useful in analyzing retinotopic organization in various visual areas of the brain and in different species.

Animals↗

Spatial frequency columns in primary visual cortex.

Using the activity-dependent 2-[14C]deoxy-D-glucose technique, we have demonstrated a columnar organization of spatial frequency--specific sensitivity in striate cortex. Cats viewing patterns containing a single spatial frequency presented at all orientations show columns of increased deoxyglucose uptake extending through all cortical layers. A control stimulus containing all spatial frequencies presented at all orientations produces no columnar density differences within the striate cortex.

Animals↗

Immunofluorescent demonstration of myeloperoxidase of phi bodies and rods in leukaemic leucocytes.

Previous studies employing enzyme histocytochemical methods based on the catalysis of the peroxidation of 3,3'-diaminobenzidine (DAB) demonstrated the presence of hydroperoxidase activity in phi bodies and rods of immature leucocytes of patients with active acute myelogenous leukaemia. It could not be determined from these studies whether the DAB oxidation product was demonstrating a single hydroperoxidase, catalase or myeloperoxidase, or both. In the present study, immunofluorescence techniques for the two hydroperoxidases were applied in an attempt to identify this activity specifically. The results obtained indicate that myeloperoxidase is present in the phi bodies and rods, and that this enzyme may be the major or the only hydroperoxidase present. Its activity could account for the peroxidation of DAB under conditions which are more favourable for the demonstration of catalase.

Catalase↗

Changes in latency and duration of neural responding following developmental auditory deprivation.

The initial latency of spikes evoked by click stimulation and the duration over which spiking occurred were observed in the inferior colliculi of rats. One ear of these animals had been deprived of early auditory stimulation by ligation of the external meatus. Clicks presented to the normally experienced ears evoked spikes in the opposite colliculus with latencies that depended on the characteristic frequency of the unit. Low-frequency (less than 5 kHz) units had latencies from 6-10 msec. Latencies declined to 3-4 msec for high frequency (greater than 20 kHz) units. After an ear had been deprived of sound from 10 days after birth, response latencies of units in the opposite colliculus with characteristic frequencies below about 10 kHz were comparable to controls, but most units above 10 kHz had latencies 2-3 times control latencies. Spike activity evoked in these units did not continue as long as that for most comparable control units. Ears sound deprived for an equal period from 60 days after birth also had changes in latencies and response durations, but these were much less than in the developmentally deprived. Latencies of gross potentials at the auditory nerve were not affected by early deprivation, indicating a central origin for the latency changes.

Acoustic Stimulation↗