Differential Expression of DSCAM Guides the Patterning of Retinal Axons Along Their Path and at Their Target in the Developing Xenopus Visual System

Background The Xenopus retinotectal circuit is organized topographically, where the dorsal-ventral axis of the retina maps respectively on to the ventral-dorsal axis of the tectum; axons from the nasal-temporal axis of the retina project respectively to the caudal-rostral axis of the tectum. Studies throughout the last two decades have shown that mechanisms involving molecular recognition of proper termination domains are at work guiding topographic organization. Such studies have shown that graded distribution of molecular cues is important for topographic mapping. However, the molecular cues organizing topography along the developing optic nerve, and as retinal axons cross the chiasm and navigate towards their target in the tectum, remain unknown. Down syndrome cell adhesion molecule (DSCAM) has been characterized as a key molecule in axon guidance, making it a strong candidate involved in the topographic organization of retinal fibers along the optic path.Methods Using a combination of whole-brain clearing and immunohistochemistry staining techniques we characterized DSCAM expression and the projection of ventral and dorsal retinal fibers starting from the eye, followed to the optic nerve into the chiasm, and into the terminal target in the optic tectum in Xenopus laevis tadpoles. We also assessed the effects of DSCAM on the establishment of retinotopic maps through spatially and temporally targeted DSCAM knockdown on retinal ganglion cells (RGCs) with axons innervating the optic tectum. Results Highest expression of DSCAM was localized to the ventral posterior region of the optic nerve and chiasm; this expression pattern coincides with ventral fibers derived from ventral RGCs. Downregulating DSCAM levels affected the segregation and proper sorting of medial axon fibers, derived from ventral RGCs, within the tectal neuropil, indicating that DSCAM plays a role in retinotopic organization. ConclusionThese findings together with the observation that DSCAM immunoreactivity accumulates on the primary dendrites of tectal neurons indicates that DSCAM exerts multiple roles in coordinating retinotopic order and connectivity in the developing vertebrate visual system.

An evolving view of retinogeniculate transmission

The thalamocortical (TC) relay neuron of the dorsoLateral Geniculate Nucleus (dLGN) has borne its imprecise label for many decades in spite of strong evidence that its role in visual processing transcends the implied simplicity of the term “relay”. The retinogeniculate synapse is the site of communication between a retinal ganglion cell and a TC neuron of the dLGN. Activation of retinal fibers in the optic tract causes reliable, rapid, and robust postsynaptic potentials that drive postsynaptics spikes in a TC neuron. Cortical and subcortical modulatory systems have been known for decades to regulate retinogeniculate transmission. The dynamic properties that the retinogeniculate synapse itself exhibits during and after developmental refinement further enrich the role of the dLGN in the transmission of the retinal signal. Here we consider the structural and functional substrates for retinogeniculate synaptic transmission and plasticity, and reflect on how the complexity of the retinogeniculate synapse imparts a novel dynamic and influential capacity to subcortical processing of visual information.

Automated Perimetry in Glaucoma

Clinical experience and multiple prospective studies, such as the Collaborative Normal Tension Glaucoma Study and the Los Angeles Latino Eye Study, have demonstrated that the diagnosis of glaucoma is more complex than identifying elevated intraocular pressure. As a result, increased emphasis has been placed on measurements of the structural and functional abnormalities caused by glaucoma. The refinement and adoption of imaging technologies assist the clinician in the detection of glaucomatous damage and, increasingly, in identifying the progression of structural damage. Because visual field defects in glaucoma patients occur in patterns that correspond to the anatomy of the nerve fiber layer of the retina and its projections to the optic nerve, visual functional tests become a link between structural damage and functional vision loss. The identification of glaucomatous damage and management of glaucoma require appropriate, sequential measurements and interpretation of the visual field. Glaucomatous visual field defects usually are of the nerve fiber bundle type, corresponding to the anatomic arrangement of the retinal nerve fiber layer. It is helpful to consider the division of the nasal and temporal retina as the fovea, not the optic nerve head, because this is the location that determines the center of the visual field. The ganglion cell axon bundles that emanate from the nasal side of the retina generally approach the optic nerve head in a radial fashion. The majority of these fibers enter the nasal half of the optic disc, but fibers that represent the nasal half of the macula form the papillomacular bundle to enter the temporal-most aspect of the optic nerve. In contrast, the temporal retinal fibers, with respect to fixation, arc around the macula to enter the superotemporal and inferotemporal portions of the optic disc. The origin of these arcuate temporal retinal fibers strictly respects the horizontal retinal raphe, temporal to the fovea. As a consequence of this superior-inferior segregation of the temporal retinal fibers, lesions that affect the superotemporal and inferotemporal poles of the optic disc, such as glaucoma, tend to cause arcuateshaped visual field defects extending from the blind spot toward the nasal horizontal meridian.

Alteration of the retinotectal projection map by the graft of mesencephalic floor plate or sonic hedgehog

The floor plate plays crucial roles in the specification and differentiation of neurons along the dorsal-ventral (DV) axis of the neural tube. The transplantation of the mesecephalic floor plate (mfp) into the dorsal mesencephalon in chick embryos alters the fate of the mesencephalon adjacent to the transplant from the tectum to the tegmentum, a ventral tissue of the mesencephalon. In this study, to test whether the mfp is involved in the specification of the DV polarity of the tectum and affects the projection patterns of retinal fibers to the tectum along the DV axis, we transplanted quail mfp into the dorsal mesencephalon of chick embryos, and analyzed projection patterns of dorsal and ventral retinal fibers to the tectum. In the embryos with the mfp graft, dorsal retinal fibers grew into the dorsal part of the tectum which is the original target for ventral but not dorsal retinal fibers and formed tight focuses there. In contrast, ventral retinal fibers did not terminate at any part of the tectum. Transplantation of Sonic hedgehog (Shh)-secreting quail fibroblasts into the dorsal mesencephalon also induced the ectopic tegmentum and altered the retinotectal projection along the DV axis, as the mfp graft did. These results suggest that some factors from the mesencephalic floor plate or the tegmentum, or Shh itself, play a crucial role in the establishment of the DV polarity of the tectum and the retinotectal projection map along the DV axis.

The netrin receptor frazzled is required in the target for establishment of retinal projections in the Drosophila visual system

Retinal axons in Drosophila make precise topographic connections with their target cells in the optic lobe. Here we investigate the role of the Netrins and their receptor Frazzled in the establishment of retinal projections. We find that the Netrins, although expressed in the target, are not required for retinal projections. Surprisingly, Frazzled, found on both retinal fibers and target cells, is required in the target for attracting retinal fibers, while playing at best a redundant role in the retinal fibers themselves; this finding demonstrates that target attraction is necessary for topographic map formation. Finally, we show that Frazzled is not required for the differentiation of cells in the target. Our data suggest that Frazzled does not function as a Netrin receptor in attracting retinal fibers to the target; nor does it seem to act as a homotypic cell adhesion molecule. We favor the possibility that Frazzled in the target interacts with a component on the surface of retinal fibers, possibly another Netrin receptor.