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C J Snider

Publications and source records attributed to C J Snider.

7 recordsLinked to original sources

Prenatal development of retinogeniculate axons in the macaque monkey during segregation of binocular inputs.

In the fetal monkey the projections from the two eyes are initially completely intermingled within the dorsal lateral geniculate nucleus (DLGN) before separating into eye-specific layers (). To assess the cellular basis of this developmental process, we examined the morphological properties of individual retinogeniculate axons in prenatal monkeys of known gestational ages. The period studied spanned the time from when binocular overlap has been reported to be maximum, circa embryonic (E) day 77 through E112, when the segregation process is already largely completed in the caudal portion of the nucleus. Retinogeniculate fibers were labeled by making small deposits of DiI crystals into the fixed optic tract. After adequate time was allowed for diffusion of the tracer, fibers were visualized by confocal microscopy, and morphometric measures were made from photomontages. This revealed that retinogeniculate fibers in the embryonic monkey undergo continuous growth and elaboration during binocular overlap and subsequent segregation. Importantly, very few side-branches were found along the preterminal axon throughout the developmental period studied. Thus, restructuring of retinogeniculate fibers does not underlie the formation of eye-restricted projections in the primate. Rather, the results support the hypothesis that binocular segregation in the embryonic monkey is caused by the loss of retinal fibers that initially innervate inappropriate territories ().

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Activity-regulated cell death contributes to the formation of ON and OFF alpha ganglion cell mosaics.

At maturity, ON and OFF alpha ganglion cells in the cat retina are arrayed in regular mosaics, with adjacent cells commonly forming ON-OFF pairs. In the present study, we investigated the role of activity-mediated ganglion cell death in the formation of such cellular patterns. Because direct measures of ganglion cell mosaics are problematic in the developing retina, we examined the distributions of ON and OFF alpha cells in the postnatal cat retina by assessing the degree to which cells in closest proximity were of opposite sign (i.e., ON-OFF pairs). Computer simulations demonstrated that superimposition of two regular distributions results in a high incidence (approximately 90%) of opposite sign pairs. This is also the case for ON and OFF alpha cells in the mature retina, reflecting the high degree of regularity exhibited by this cell class. In contrast, during the first postnatal month, alpha cells displayed a much lower incidence of opposite sign pairs (approximately 60%), comparable to the superimposition of two simulated random distributions. We also show that there is a 20% loss of alpha cells in the central retina during postnatal development and that this magnitude of loss is sufficient to form regular distributions of ON and OFF cells. To assess the influence of sodium voltage-gated activity on this developmental process, intraocular injections of tetrodotoxin (TTX) were made during the postnatal period of alpha cell loss. When the TTX-treated animals reached maturity, there was a dose-related decrease in the incidence of opposite sign pairs, without any appreciable change in cell density. Moreover, the regularity index of ON and OFF cells was significantly lower than normal in the TTX-treated retinas. These findings demonstrate that a spatially selective pattern of ganglion cell loss contributes to the formation of regular ON and OFF ganglion cell distributions and that such cell loss is regulated by retinal activity.

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Topographic specificity in the retinocollicular projection of the developing ferret: an anterograde tracing study.

To assess the degree of order exhibited during development by crossed and uncrossed retinocollicular pathways, focal deposits of 1,1'-dioctodecyl-3,3,3'3'-tetramethylinodocarbocyanine perchlorate (DiI) were made into the temporal or nasal retina of prenatal and postnatal ferrets. This procedure revealed that the first retinal fibers (from the ipsilateral temporal retina) grow into the superior colliculus at embryonic (E) day 30. Both crossed and uncrossed fibers innervate the colliculus by E34. At this age, terminal arbors were lacking, and there was no evidence of extensive axonal branching. Retinocollicular arbors first appeared at E38, with both the crossed and uncrossed projections forming well-defined terminal zones that appeared to be localized to topographically appropriate regions. At E38, the ipsilateral terminal zone was significantly larger but notably less dense than the contralateral zone. At this and later ages (postnatal day [P] 0 and P7), a few crossed and uncrossed fibers extended beyond the terminal zone. Four days later, at P0, the terminal zone of the uncrossed projection was reduced in size in comparison with that of earlier ages, whereas the crossed projection became substantially larger. By P7, the few misprojecting fibers seen in younger ferrets had been virtually eliminated. When focal retinal deposits of tracer were made into the nasal retina of E36 and E40 ferrets, crossed fibers were found to innervate the caudal segment of the superior colliculus. These crossed nasal cells appear to project to the topographically appropriate region of the superior colliculus (caudal segment) but on the wrong side of the brain. Collectively, the present findings indicate that throughout development the ferret retinocollicular pathway is characterized by a remarkable degree of topographic precision as evident by the paucity of axonal branches and the low number of grossly misprojecting axons.

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Topographic organization in the retinocollicular pathway of the fetal cat demonstrated by retrograde labeling of ganglion cells.

The topographic organization of the developing retinocollicular pathway was assessed by making focal deposits of a retrograde tracer (usually rhodamine latex beads) into the superficial layers of the superior colliculus of fetal cats at known gestational ages. Subsequently, the distributions of labeled cells in the contralateral and ipsilateral retinas were examined. At all stages of development, a high density of labeled cells was found in a delimited area (core region) of both retinas. The locations of the retinal regions containing the high density of labeled cells varied with the locus of the tracer deposit in the superior colliculus in a manner consistent with the topographic organization of the mature cat's retinocollicular pathway. Additionally, some labeled ganglion cells, considered to be ectopic, were found to be scattered throughout the contralateral and ipsilateral fetal retinas. Such ectopic cells were few in number throughout prenatal development. For every 100 cells projecting to the appropriate region of the colliculus, we estimate that less than one ganglion cell makes a gross projection error. The incidence of ectopic cells did not differ between the contralateral and ipsilateral retina, even though the overall density of crossed labeled cells was always greater than that of uncrossed labeled cells. In the youngest fetal animals, tracer deposits into the caudal portion of the superior colliculus resulted in a core region of labeled cells in the contralateral nasal retina as well as in the nasal ipsilateral retina. Such uncrossed nasal cells, not seen in more mature animals, appear to innervate the appropriate topographic location of the superior colliculus, but on the wrong side of the brain. Most likely, these uncrossed nasal ganglion cells contribute to the widespread distribution of the ipsilateral retinocollicular pathway observed in fetal cats after intraocular injections of anterograde tracers (Williams and Chalupa, 1982). Collectively, our findings demonstrate that the developing retinocollicular pathway of the fetal cat is characterized by a remarkable degree of topographic precision.

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Callosal projection neurons in area 17 of the fetal rhesus monkey.

We have studied the distribution of callosal projection neurons in area 17 of a fetal rhesus monkey which received large injections of horseradish peroxidase into the contralateral occipital cortex. In comparison to other cortical areas, area 17 contains few callosal projection neurons. Most of these cells are confined to a region extending tangentially about 2.5 mm from the 17/18 border, although a few neurons were noted as much as 5 mm from the border. Comparing the distribution of callosal projection neurons in the fetal monkey with what has been described in newborn and adult macaques, it is apparent that although some degree of refinement in striate callosal connections may occur during in utero development, the prenatal development of callosal connections in the macaque is inherently adult-like.

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Voltage-dependent sodium channel alpha subunit immunoreactivity is expressed by distinct cell types of the cat and monkey retina.

Polyclonal (7493 and 7317) and monoclonal (mAb3) antibodies, generated to the alpha subunit of the voltage-gated sodium channel (alpha NaCh), were employed to assess the cell types containing alpha NaCh-like immunoreactivity in the mature cat and monkey retina. Immunoblot analyses of retinal proteins in the cat revealed that the polyclonal and monoclonal antibodies we employed labeled a band in the 260-kDa region which corresponds to the molecular mass of the alpha subunit of the NaCh. In both the cat and monkey, these antibodies immunolabeled several distinct types of retinal cells. With the polyclonal antibodies immunoreactivity was observed in ganglion cells and their intraretinal axons, in horizontal cells, and unexpectedly, in cones. In addition, in both species, a limited number of heavily labeled profiles, presumed to be bipolar cells, were seen in the inner nuclear layer. In cat and monkey the monoclonal antibody labeled axons in the fiber layer, ganglion cell somata, and a continuous band of immunoreactive cell bodies (presumed bipolar cells) situated in the outer half of the inner nuclear layer. By immunolabeling isolated cells dissociated from the cat retina, it was possible to demonstrate unequivocally that a population of bipolar cells was labeled by the monoclonal and the polyclonal antibodies we employed. The differences in the labeling observed with the monoclonal antibody as compared to the polyclonal antibodies were interpreted as reflecting the presence of different alpha-subunit subtypes in the mammalian retina. Collectively, our findings suggest that alpha NaCh-like proteins are expressed by a more diverse population of retinal cells than expected on the basis of previous physiological and immunohistochemical studies.

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