PubMed Health⌕ Search

Biomedical subjects

S B Tieman

Publications and source records attributed to S B Tieman.

At least 19 recordsLinked to original sources

N-acetylaspartylglutamate immunoreactivity in human retina.

The acidic dipeptide N-acetylaspartylglutamate (NAAG), which satisfies many of the criteria for a neurotransmitter, was identified immunohistochemically within two human retinae. We observed NAAG immunoreactivity in retinal ganglion cells, their dendrites in the inner plexiform layer, and their axons in the optic nerve fiber layer. The vast majority of ganglion cells were stained, including displaced ganglion cells, ganglion cells of different sizes, and those whose dendrites arborized in the inner and outer sublaminae of the inner plexiform layer, that is, presumed On- and Off- cells. The sizes of labeled and unlabeled cells in the ganglion cell layer, as measured in counterstained material, suggest that the unlabeled cells consist primarily or only of displaced amacrine cells. We also saw immunoreactivity in small cells along the inner margin of the inner nuclear layer, presumably amacrine cells, and in small cells with little cytoplasm in the inner plexiform and ganglion cell layers, presumably displaced amacrine cells. These results are consistent with a role for NAAG in the transmission of visual information from the retina to the rest of the brain. Further, they are similar to those reported previously in rat, cat and monkey, thus demonstrating the relevance of previous studies to humans.

Aged↗

Dark-rearing fails to affect the basal dendritic fields of layer 3 pyramidal cells in the kitten's visual cortex.

The development of the cat's visual cortex is incomplete at birth and is influenced by the cat's early visual experience. We have previously demonstrated that the basal dendritic fields of layer 3 pyramidal cells grow substantially during the first 5 weeks after birth and that stripe-rearing affects their orientation. In this paper we determined the effects on these dendritic fields of visual deprivation (dark-rearing) during the first 3 months of life. The visual cortices of both normally reared and dark-reared cats were impregnated by the Golgi method, sectioned in the tangential plane and counterstained. The basal dendritic fields of completely impregnated pyramidal cells from layer 3 were drawn with the aid of a camera lucida, and compared in terms of number and length of primary dendrites, branching, size, elongation, and distribution of dendritic field orientations. Surprisingly, we observed no significant differences in any parameter measured. Thus, although stripe-rearing can specifically alter the orientation of the dendritic fields of the layer 3 pyramidal cells, and dark-rearing has been shown by others to alter the size of layer 4 stellate cells, dark-rearing failed to affect the dendritic fields of layer 3 pyramidal cells.

Animals↗

Development of the dendritic fields of layer 3 pyramidal cells in the kitten's visual cortex.

The cat's visual cortex is immature at birth and undergoes extensive postnatal development. For example, cells of layers 2 and 3 do not complete migration until about 3 weeks after birth. Despite the importance of dendritic growth for synaptic and functional development, there have been few studies of dendritic development in the cat's visual cortex to correlate with numerous studies of functional and synaptic development. Accordingly, we used the Golgi method to study the development of the dendrites of layer 3 pyramidal cells in the visual cortex of a series of cats ranging in age from 2 days to 3 years. Blocks of visual cortex were impregnated by the Golgi-Kopsch method and sectioned in the tangential plane. Layer 3 pyramidal cells were drawn with a camera lucida and analyzed by Sholl diagrams and vector addition. In kittens < 1 week old, these cells were very immature, with only an apical dendrite and no basal dendrites. Basal dendrites appeared during the second week. By 2 weeks, all of the basal dendrites had emerged from the soma, but they had few branches and were tipped with growth cones. By 4 weeks, they had finished branching but continued to grow in length until, by 5 weeks, they reached their adult size. Examination of the basal dendritic fields in the tangential plane revealed that their dendritic fields were more elongated at 2 weeks than at later ages, perhaps because of their smaller size. The distribution of dendritic field orientations was uniform at all ages except 3 and 4 weeks, when there was a preponderance of fields oriented in the rostrocaudal direction. Because dendritic growth and branching occurred very rapidly over a period that precedes and overlaps with the peak periods of synaptogenesis and of sensitivity to the effects of early visual experience, they may depend on afferent visual activity. The early emergence of primary dendrites, however, suggests that this process is independent of afferent activity. The coincident timing of dendritic branching with the presence of dendritic growth cones suggests that branching may occur at growth cones.

Aging↗

Relay cells, not interneurons, of cat's lateral geniculate nucleus contain N-acetylaspartylglutamate.

N-acetylaspartylglutamate (NAAG) is an endogenous brain dipeptide that satisfies many of the criteria for a neurotransmitter. We have previously identified NAAG immunoreactivity in neurons of the lateral geniculate nucleus (LGN) of the cat and monkey. To determine whether all LGN neurons contain NAAG, we treated sections of cat LGN with affinity-purified antibodies to NAAG and counterstained them with thionin. The larger neurons contained NAAG, but the smaller neurons did not. We treated other sections with antiserum to glutamic acid decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), in order to label interneurons of the LGN. In these sections, the smaller cells were labeled; the larger neurons were not. We hypothesized that NAAG was present in relay cells, but not interneurons. We used two double-labeling paradigms to test this hypothesis. We combined immunocytochemistry for NAAG using a fluorescent secondary antibody with either (1) fluorescent retrograde tracers (true blue, granular blue, rhodamine beads, or propidium iodide) injected into areas 17 and/or 18 or (2) immunocytochemistry for GAD using a second fluorescent secondary antibody. In the LGN, over 99% of retrogradely labeled cells contained NAAG, but few GAD-positive neurons did. In contrast, neurons of the perigeniculate nucleus contained both NAAG and GAD, demonstrating that staining by one set of antisera did not inhibit staining by the other and that perigeniculate neurons are chemically distinct from the interneurons of the LGN. We conclude that in LGN, the relay cells, which project to visual cortex, contain NAAG, whereas most of the interneurons, which contain GABA, do not.

Animals↗

N-acetylaspartylglutamate immunoreactivity in neurons of the monkey's visual pathway.

The acidic dipeptide N-acetylaspartylglutamate (NAAG) was identified immunohistochemically within neurons of the visual pathways of two adult macaque monkeys which had undergone midsagittal sectioning of the optic chiasm 6 or 9 years earlier. In both temporal and nasal retinae, amacrine cells, including some displaced amacrine cells, expressed NAAG immunoreactivity. In temporal but not nasal retina, retinal ganglion cells were stained, as were their dendrites in the inner plexiform layer, and their axons in the optic nerve fiber layer. In nasal retina, the ganglion cells had degenerated because they were axotomized by the optic chiasm section. In the target regions of the retinal ganglion cells, the superior colliculus and the lateral geniculate nucleus (LGN), both neuropil and cell bodies were stained. In LGN, staining was confined to layers 2, 3, and 5, that is, to the layers innervated by the intact ipsilateral pathway. Immunoreactivity was also seen in the cells of layers 2, 3A, 4B, 5, and 6 of area 17 and layers 3 and 5 of area 18. The neuropil was stained in all layers of area 17, but more heavily in layers 1, 2, 4B, the bottom of 4C beta, 5B, and 6B. Within 4C the staining was patchy; in tangential sections there were alternating bands of light and dark label which matched the ocular dominance bands demonstrated by cytochrome oxidase histochemistry in adjacent sections. This banding pattern is consistent with the presence of NAAG in geniculocortical terminals of the intact ipsilateral pathway and the absence of such terminals for the contralateral pathway, which had undergone transneuronal degeneration due to the optic chiasm sectioning. Overall, our results for monkey are very similar to those in cat and suggest that NAAG or a structurally related molecule may have a prominent role in the communication of visual signals at retinal, thalamic, and cortical levels.

Animals↗

Effect of eye removal on N-acetylaspartylglutamate immunoreactivity in retinal targets of the cat.

The endogenous brain dipeptide N-acetylaspartylglutamate (NAAG) has previously been demonstrated in the somata of retinal ganglion cells and the neuropil of retinal targets. In this paper we report that the NAAG immunoreactivity of the neuropil in the retinal targets is dependent on an intact optic pathway. Removal of one eye produced a marked decrease in the staining of the neuropil in layer A of the contralateral geniculate nucleus (LGN) and layer A1 of the ipsilateral LGN. There was also decreased staining in the superficial layers of the superior colliculus contralateral to the removal. These results suggest that NAAG is present in the terminals of retinal ganglion cells and is consistent with a role for NAAG in visual synaptic transmission.

Animals↗

Morphological changes in the geniculocortical pathway associated with monocular deprivation.

To summarize (Fig. 10), the structural consequences of monocular deprivation include the following changes: the relay cells in the binocular segments of the deprived geniculate layers shrink and contain less of the possible neurotransmitter NAAG. These changes appear to be secondary to a loss of terminal synaptic arbor. Certainly, deprived geniculocortical cells project to smaller ocular dominance patches in layer IV of visual cortex, where they make fewer and abnormal synapses. As a result, they activate ocular activation columns that, in addition to being small, are faint and usually fail to extend into extragranular layers. This failure to extend to other layers probably results from a failure of the poorly activated deprived-eye cells in layer IV to compete successfully with neighboring experienced-eye cells in layer IV, resulting in a loss of connections from layer IV to other layers (Fig. 11). Thus, the primary effect of monocular deprivation is probably the disruption of the geniculocortical synapse, with the other changes, such as cell size, and possibly the change in neurotransmitter content, being secondary. The disrupted synapse would result in poorly driven cortical cells and faint ocular activation columns, which in turn would bias a secondary competition for access to cells in extragranular layers. There are certain general principles that unite the findings presented in this chapter with the others in this session. First, there are similarities in the types of morphological changes observed, for example, changes in the number and size of synaptic terminals, as well as mitochondrial changes. This implies that there are similar changes during development and adult plasticity and also similar changes in vertebrates and invertebrates. Second, it is not so much the amount of activity that determines these changes, but the pattern of activity. In my results, the relative imbalance in activity is important, but not the absolute amount (for example, the columns activated by the 8-hr eye of an AME 8/1 are different from those activated by the 8-hr eye of an AME 8/8). Similarly, the binocular segment, where there was an imbalance and competition could occur, was affected, whereas the monocular segment, where there was no imbalance and competition could not occur, was not. Finally, the recent results of Reiter and Stryker suggest that monocular deprivation produces changes only when the activity of the presynaptic cell and the postsynaptic cell are correlated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Binocular competition affects the pattern and intensity of ocular activation columns in the visual cortex of cats.

The effect of binocular competition on the development of ocular activation columns in areas 17 and 18 of cats was studied using the 14C-2-deoxyglucose (14C-2DG) technique to visualize the regions of cortex activated by one eye in cats reared with equal alternating monocular exposure (equal AME), unequal AME, or monocular deprivation (MD). The average size of the ocular activation columns of the eye stimulated during administration of 2DG was positively correlated with the competitive advantage during rearing. In order of increasing percentage of visual cortex activated, the eyes were (1) deprived eye of MD cats, (2) less experienced eye of unequal AME cats, (3) either eye of equal AME cats, (4) more experienced eye of unequal AME cats, and (5) experienced eye of MD cats. In area 17, the shape of the activation columns also was affected by the relative experience of the eye. The columns of the deprived eye of MD cats were widest in layer IV, where they were about the same width as those of the less experienced eye of the unequal AME cats; in other layers they were narrower, sometimes disappearing altogether. In contrast, the activation columns of the less experienced eye of the unequal AME cats were about the same width in all layers. These results suggest that when one eye is placed at a severe disadvantage and receives no patterned input, as in MD, both geniculocortical connections and intracortical connections may be disrupted, but when the disadvantage is less, as in unequal AME, only the geniculocortical connections are disrupted. Binocular competition also affected the intensity of activation within columns in area 17. We used video densitometry to determine ratios of the amount of label in cortical and thalamic structures. Both the ratio of label in area 17 to that in the lateral geniculate nucleus (LGN) and the ratio of label in the binocular segment of area 17 to that in the monocular segment were significantly less for the deprived eye of MD cats than for any other group. These results suggest that even within the smaller activation columns, deprived geniculocortical afferents are relatively ineffective at driving cortical cells. This finding is consistent with earlier reports that the synapses from the deprived pathway are both morphologically abnormal and reduced in number. The cortical labeling for the less experienced eye of the unequal AME cats and the experienced eye of the MD cats were also significantly less than that in equal AME cats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of prenatal alcohol exposure on the sexually dimorphic nucleus of the preoptic area of the hypothalamus in male and female rats.

Prenatal alcohol exposure can produce a variety of behavioral and physiological alterations, including changes in sexually dimorphic behaviors. It has been proposed that alcohol alters these behaviors by altering prenatal androgen and/or other steroid levels. This study was designed to examine the effects of prenatal alcohol exposure on a sexually dimorphic neuroanatomical structure, namely, the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN-POA). This nucleus is larger in males than females and is sensitive to perinatal sex steroid exposure. The SDN-POA was examined in 70-80-day-old male and female rats whose mothers received on days 6-20 of pregnancy either a liquid diet containing 35% ethanol-derived calories (EDC) or a 0% EDC isocaloric pair-fed liquid diet. An ad libitum lab chow control group was also included (LC). Both volume and average cell size of the SDN-POA were markedly smaller in alcohol-exposed males relative to 0% EDC and LC controls. In contrast, prenatal alcohol exposure did not appear to affect SDN-POA volume or cell size in females. Prenatal alcohol exposure did not significantly alter the volume of a nearby nucleus, the nucleus of the anterior commissure, in either sex. These findings support the hypothesis that prenatal alcohol exposure alters sexual differentiation in males, perhaps by altering some aspect of the prenatal androgen environment. The absence of any effect in 35% EDC females suggests that males and females may be differentially sensitive to alcohol's effects on this nucleus.

Animals↗

N-acetylaspartylglutamate immunoreactivity in neurons of the cat's visual system.

The acidic dipeptide, N-acetylaspartylglutamate (NAAG) was identified immunohistochemically within neurons of the cat's visual system. In the retina, NAAG-like immunoreactivity was observed in some horizontal and amacrine cells at the inner and outer margins of the bipolar cell layer. NAAG-like immunoreactivity was also observed in many retinal ganglion cell bodies, their neurites, and the neuropil of their target areas, the lateral geniculate nucleus (LGN) and the superior colliculus. Additionally, peptide immunoreactivity was also seen in the projection neurons of the LGN, in cells of the pulvinar nucleus, and in the pyramidal cells of layers III and V in areas 17, 18 and 19 of the cerebral cortex. These data suggest that NAAG or a structurally related molecule may have a prominent role in the communication of visual signals at retinal, thalamic and cortical levels.

Animals↗

A computer-assisted video technique for preparing high resolution pictures and stereograms from thick specimens.

A computer-assisted video technique is presented for rapidly and accurately gathering, storing and depicting three-dimensional anatomical structures in thick specimens. Several optical sections through the specimen are combined to produce high-resolution photographs with essentially infinite depth-of-field. Further, the depth information implicit in the series of optical sections makes the creation of stereoscopic pairs relatively simple. The technique employs a real-time digitizing frame store and a computer. A video camera is attached to a microscope and successive optical sections are stored digitally as the plane of focus is systematically changed. After storage, the image of each optical section is enhanced to emphasize elements that are sharply focussed. The final two-dimensional image is generated by selecting for each point in the final picture the darkest grey value occurring at the corresponding point in any of the pictures in the through-focus series. A picture with essentially infinite depth-of-field is produced when points of correspondence in the series are determined by a ray passing normal to the plane of optical section. Right and left pictures for a stereoscopic pair are produced when points of correspondence are determined by a ray slanting either left or right of normal. This technique is illustrated with cobalt chloride-filled neurons from whole-mounted cricket ganglia, with HRP-filled axons from whole-mounted goldfish tectum, with Golgi-Kopsch-impregnated neurons from cat visual cortex, and with sections of cobalt chloride-filled antennal afferents in cricket.

Algorithms↗

Eye-specific segregation of optic afferents in mammals, fish, and frogs: the role of activity.

Eye-specific patches or stripes normally develop in the visual cortex and superior colliculus of many (but not all) mammals and are also formed, after surgically produced binocular innervation, in the optic tectum of fish and frogs. The segregation of ocular dominance patches or columns has been studied using a variety of anatomical pathway-tracing techniques, by electrophysiological recording of postsynaptic units or field potentials, and by the 2-deoxyglucose method following visual stimulation of only one eye. In the tectum of both fish and frogs and in the cortex and colliculus of mammals, eye-specific patches develop from initially diffuse, overlapping projections. Of the various mechanisms that might cause such segregation, the evidence favors an activity-dependent process that stabilizes synapses from the same eye because of their correlated activity. First, several environmental manipulations affect the segregation of afferents in visual cortex: strabismus and alternate monocular exposure apparently enhance segregation, whereas dark rearing slows the segregation process, and monocular deprivation causes the experienced eye to form larger patches at the expense of those of the deprived eye. Second, blocking activity in both eyes is effective in preventing the segregation both in the tectum of fish and frog and in the visual cortex of cat. With the eyes blocked, alternate stimulation of the optic nerves permits the segregation of ocular dominance, at least onto single cells in the cat visual cortex. These findings are discussed in terms of an activity-dependent stabilization of those synapses having correlated activity (those from neighboring ganglion cells within one eye) but not of those lacking correlated activity (those from left and right eyes). We suggest that the eye-specific patches represent a compromise between total segregation of the projections from the two eyes and the formation of a single continuous retinotopic map across the surface of the cortex or tectum.

Animals↗

The anatomy of geniculocortical connections in monocularly deprived cats.

In monocularly deprived (MD) cats, many cells in the lateral geniculate nucleus (LGN) but few cells in the visual cortex respond to input from the deprived eye, suggesting that the connections to visual cortex from the deprived geniculate laminae may have been disrupted. It has been known for some time that the afferents representing the deprived eye terminate over a smaller percentage of layer IV than do those representing the experienced eye, but it is becoming increasingly clear that this alone cannot explain the inability of the deprived pathway to activate cortical cells. 2-Deoxyglucose studies of ocular dominance columns in MD cats have shown that the columns are often (a) restricted to layer IV, suggesting that intracortical connections may be disrupted, and (b) very faint, suggesting that MD alters the efficacy of the deprived pathway in addition to restricting its territory. Electron microscopy has shown that both deprived and experienced afferents end in terminals that contain mitochondria and round synaptic vesicles and that make asymmetric contacts with dendritic profiles. However, the terminals of deprived afferents differ from those of experienced afferents: they are 25% smaller, contain 33% fewer mitochondria, are more likely to make synapses that are presynaptically convex (and thus, perhaps, immature), make fewer perforated synapses, and synapse onto smaller spines. Further, the geniculocortical axons from deprived laminae appear to end in fewer synaptic terminals, than do those from the experienced laminae. The finding that the synaptic terminals of deprived afferents are both abnormal morphologically and fewer in number can help to explain the reduced effectiveness of the deprived eye in driving cortical cells but does not rule out additional effects such as suppression and loss of intracortical connectivity.

Animals↗

Effects of unequal alternating monocular exposure on the sizes of cells in the cat's lateral geniculate nucleus.

In unequal alternating monocular exposure, each eye receives normal patterned input, but on alternate days and for unequal periods. This imbalance in stimulation produces a behavioral deficit for the less-experienced eye and alters the ability of that eye to activate cortical cells. To determine whether unequal alternating exposure also affects the sizes of cells in the lateral geniculate nucleus (LGN), we measured the cross-sectional areas of geniculate neurons in seven normally reared cats, 14 cats reared with equal alternating exposure, and 17 cats reared with unequal alternating exposure. We found that, in the LGNs of cats reared with unequal alternating monocular exposure, cells in layers that received their input from the less-experienced eye were smaller than those in layers that received their input from the more-experienced eye. This effect was restricted to the binocular segments of the nucleus, and the difference in cell size was a function of the imbalanced exposure, rather than the length of exposure per se. In control groups given balanced alternating exposure, cell size was not correlated with the length of daily exposure. In cats reared with unequal exposure, the change in cell size was greater in the nucleus ipsilateral to the less-experienced eye. Further, the size of the effect was correlated with the size of the imbalance imposed during rearing: Cats reared with a moderate imbalance (8 hours/day vs. 4 hours/day) showed less change in cell size than cats reared with a large imbalance (8 hours/day vs. 1 hour/day). These results are consistent with those of behavorial and physiological studies and strongly suggest (1) that unequal alternating monocular exposure affects the sizes of cells in the LGN by altering the normal competitive balance between the retinogeniculocortical pathways from the left and right eyes, and (2) that the contralateral pathway has some inherent advantage in this competition. We also found a slight shrinkage of cells in the LGNs of cats reared with equal alternating monocular exposure. Since this effect was restricted to the binocular segments of the nucleus, and was not related to the length of exposure given, it was probably caused by the imbalanced binocular competition that occurred during each day's monocular exposure.

Animals↗

Effects of monocular deprivation on geniculocortical synapses in the cat.

In monocularly deprived (MD) cats, many cells in the lateral geniculate nucleus (LGN) but few cells in the visual cortex respond to input from the deprived eye, suggesting that the connections to visual cortex from the deprived geniculate laminae may have been disrupted. I have examined these connections in MD cats by using electron microscopic autoradiography of visual cortex after injections of tritiated lysine into single laminae of LGN. After injections into either deprived or experienced laminae, there was label over terminals that contained mitochondria and round synaptic vesicles and that made asymmetric contacts with dendritic profiles. However, the terminals of deprived afferents differed from those of experienced afferents. They were 25% smaller, contained 33% fewer mitochondria, were more likely to make synapses that were presynaptically convex (and thus, perhaps, immature), and synapsed onto smaller spines. These morphological changes were greater for afferents to upper layer IV than for afferents to lower layer IV. The geniculocortical synapses from deprived laminae were also reduced in number. To correct for variations in injection size and for a probable reduction in protein synthesis by cells in the deprived laminae, I computed the ratio of labeled synaptic terminals to labeled myelinated axons. Injections into the deprived laminae labeled 43% fewer synaptic terminals per labeled myelinated axon than did injections into the experienced lamina. The finding that the synaptic terminals of deprived afferents are both abnormal morphologically and fewer in number can help to explain the reduced effectiveness of the deprived eye in driving cortical cells.

Animals↗

Behavioral and physiological effects of monocular deprivation: a comparison of rearing with diffusion and occlusion.

To compare the effects of monocular deprivation produced by occlusion and diffusion, 9 cats were reared in the dark from birth to 4 weeks of age, when they were brought out for periods of exposure with one eye covered. For 3 cats, the left eye was covered with a white diffuser while the right eye received 8 h of normal patterned exposure (MD/D-8). For 2 cats, the left eye was covered with a black occluder while the right eye was exposed for 8 h (MD/O-8), and for 4 cats, the right eye was covered with a black occluder while the left eye was exposed for 1 h (MD/O-1). Monocular exposure continued until the cats were 3 months old, when they began receiving binocular exposure. For all cats, the visual field of the exposed eye was normal. For the MD/D cats, the field of the pattern-deprived eye was restricted to the monocular crescent, and resembled the fields of monocularly lid-sutured cats. In contrast, for the MD/O cats, the field of the pattern-deprived eye was much larger, extending nearly to the midline. Thus, monocular diffusion produced more restricted visual fields than did monocular occlusion. Preliminary physiological data from the MD/D-8 and MD/O-8 cats showed that more cortical cells responded to stimulation of the pattern-deprived eye in the MD/O-8 cats than in the MD/D-8 cats. Taken together with our earlier results on cats reared with unequal patterned input to the two eyes, these results further suggest that there is a temporal-to-nasal gradient in sensitivity to the effects of an imbalance in stimulation to the two eyes.

Animals↗

Removal of the more-experienced eye decreases visual field deficits in cats reared with unequal alternating monocular exposure.

Unequal alternating monocular exposure produces a nasal field deficit for the less-experienced eye, which persists despite prolonged unrestricted binocular exposure. We now report that this deficit decreases after the more experienced eye is removed. Prior to enucleation, the visual field of the less-experienced eye was restricted to the temporal hemifield; 5 months after enucleation of the more-experienced eye, this field extended into the nasal field. Our results are consistent with those in monocularly-deprived cats, and with the occasional recovery of human amblyopes after loss of the fixating eye.

Animals↗