Ipsilateral Retinal Ganglion Cell Research Articles

Development of Single Retinofugal Axon Arbors in Normal and β2 Knock-Out Mice

The maturation of retinal ganglion cell (RGC) axon projections in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) relies on both molecular and activity-dependent mechanisms. Despite the increasing popularity of the mouse as a mammalian visual system model, little is known in this species about the normal development of individual RGC axon arbors or the role of activity in this process. We used a novel in vivo single RGC labeling technique to quantitatively characterize the elaboration and refinement of RGC axon arbors in the dLGN and SC in wild-type (WT) and β2-nicotinic acetylcholine receptors mutant (β2(-/-)) mice, which have perturbed retinal waves, during the developmental period when eye-specific lamination and retinotopic refinement occurs. Our results suggest that eye-specific segregation and retinotopic refinement in WT mice are not the result of refinement of richly exuberant arbors but rather the elaboration of arbors prepositioned in the proper location combined with the elimination of inappropriately targeted sparse branches. We found that retinocollicular arbors mature ∼1 week earlier than retinogeniculate arbors, although RGC axons reach the dLGN and SC at roughly the same age. We also observed striking differences between contralateral and ipsilateral RGC axon arbors in the SC but not in the LGN. These data suggest a strong influence of target specific cues during arbor maturation. In β2(-/-) mice, we found that retinofugal single axon arbors are well ramified but enlarged, particularly in the SC, indicating that activity-dependent visual map development occurs through the refinement of individual RGC arbors.

Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc

The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell (RGC) axons at the optic chiasm is essential for the establishment of binocular vision. Contralateral axons cross the chiasm midline as they progress from the optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline. The molecular mechanism underlying this phenomenon is not completely understood. Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in ipsilateral RGCs of the developing retina. Together with the presence of Shh at the midline, this complementary expression pattern led us to hypothesize that Shh might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis, we found that only Boc-positive RGC axons retract in vitro in response to Shh and that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is required for the normal segregation of ipsilateral axons at the optic chiasm and, conversely, that Boc expression in contralateral RGCs prevents their axons from crossing the optic chiasm. Together, these results suggest that Shh repels ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work identifies a novel molecular pathway required for the segregation of axons at the optic chiasm.

Kainic acid intraocular injections during the postnatal critical period induce plastic changes in the visual system

Changes in the retino-collicular projection and in the number of optic nerve (ON) axons in adult rats were analyzed after partial loss of retinal ganglion cells (RGCs), induced by intravitreal injections of kainic acid (KA) on postnatal days 2–3 (P2–P3) or 10–12 (P10–P12). KA injected at P2–P3 decreased the volume of the adult contralateral superior colliculus (SC) and the density of the retino-collicular contralateral projection, but maintained the neonatal pattern in the ipsilateral projection from the un-injected eye. ON axon number was significantly increased in the un-injected eye but decreased in the KA-injected eye. Thus, restriction of the ipsilateral retino-collicular projection and RGC death in the un-injected eye are modified by KA at P2–P3, during the postnatal critical period, but not at P10–P12, after it is over. We suggest that, in the SC contralateral to the KA-injected eye, the disappearance of axon terminals belonging to RGC killed by KA would decrease competition between ipsilateral and contralateral terminals, thus contributing to maintaining the neonatal pattern in the ipsilateral retino-collicular projection. The reduction in RGC death in the un-injected eye could also be related to the disappearance of RGC terminals in the contralateral SC, which would have increased neurotrophic factor availability.

A Role for Nr-CAM in the Patterning of Binocular Visual Pathways

Retinal ganglion cell (RGC) axons diverge within the optic chiasm to project to opposite sides of the brain. In mouse, contralateral RGCs are distributed throughout the retina, whereas ipsilateral RGCs are restricted to the ventrotemporal crescent (VTC). While repulsive guidance mechanisms play a major role in the formation of the ipsilateral projection, little is known about the contribution of growth-promoting interactions to the formation of binocular visual projections. Here, we show that the cell adhesion molecule Nr-CAM is expressed by RGCs that project contralaterally and is critical for the guidance of late-born RGCs within the VTC. Blocking Nr-CAM function causes an increase in the size of the ipsilateral projection and reduces neurite outgrowth on chiasm cells in an age- and region-specific manner. Finally, we demonstrate that EphB1/ephrin-B2-mediated repulsion and Nr-CAM-mediated attraction comprise distinct molecular programs that each contributes to the proper formation of binocular visual pathways.

Glia, neurons, and axon pathfinding during optic chiasm development

The importance of vision in the behavior of animals, from invertebrates to primates, has led to a good deal of interest in how projection neurons in the retina make specific connections with targets in the brain. Recent research has focused on the cellular interactions occurring between retinal ganglion cell (RGC) axons and specific glial and neuronal populations in the embryonic brain during formation of the mouse optic chiasm. These interactions appear to be involved both in determining the position of the optic chiasm on the ventral diencephalon (presumptive hypothalamus) and in ipsilateral and contralateral RGC axon pathfinding, developmental events fundamental to binocular vision in the adult animal.

The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi). IV. Bilateral projections and the binocular visual field.

Infusion of cobaltous-lysine into the optic nerve of juvenile Florida garfish reveals that the preoptic area, pretectum, thalamus and the mediorostral and ventrolateral poles of the optic tectum each receive bilateral, monosynaptic input. The bilateral input to the mediorostral pole of the tectum projects via the dorsal optic tract and terminates in the rostral half of the tectum. The bilateral input to the ventrolateral tectum projects via the ventral optic tract and extends the whole length of the tectum. The incidence of direct ipsilateral input to the tectum suggests binocular vision may play a functional role in the survival of this species. In order to test this hypothesis, we examined the retinal distribution of ipsilateral retinal ganglion cells that project to the mediorostral tectum and the size and location of the binocular visual field. Cell distribution was examined by retrograde labelling with rhodamine-conjugated dextran amine delivered by microinjections into the mediorostral pole of the right optic tectum. In the ipsilateral retina, ganglion cells are distributed in a narrow temporoventral area with a mean of 0.44 +/- 0.14 x 10(3) cells per mm2 apposing the retinal margin. In the contralateral retina, ganglion cells are also distributed within this temporoventral region with a mean peak density of 2.33 +/- 0.47 x 10(3) cells per mm2. Three broad classes of ipsilaterally projecting retinal ganglion cells (orthotopic cells within the ganglion cell layer, displaced cells within the inner nuclear layer, and giant cells within the ganglion and inner nuclear layers) are identified, intermingled in both the ipsilateral and contralateral retinae after retrograde labelling from the mediorostral pole of the tectum. Ophthalmoscopic mapping of the monocular and binocular visual fields reveals two small frontal wedges of binocular overlap. A dorsal wedge (12 degrees wide) extends from approximately 7 degrees above the horizontal axis to 10 degrees beyond the vertical axis, and a ventral wedge (20 degrees wide) extends approximately 10 degrees below the horizontal axis to 15 degrees beyond the vertical axis. The dorsal binocular visual field is subtended by the temporoventral region of the retina possessing both ipsilaterally and contralaterally projecting ganglion cells which terminate in the mediorostral pole of the optic tectum. Therefore, the partial decussation of retinal ganglion cell axons at the optic chiasm brings information from corresponding regions of the binocular visual field into register in the mediorostral pole of the optic tectum.(ABSTRACT TRUNCATED AT 250 WORDS)

The Visual System of the Florida Garfish, <i>Lepisosteus platyrhincus</i>(Ginglymodi) (Part 2 of 2)

Infusion of cobaltous-lysine into the optic nerve of juvenile Florida garfish reveals that the preoptic area, pretectum, thalamus and the mediorostral and ventrolateral poles of the optic tectum each receive bilateral, monosynaptic input. The bilateral input to the mediorostral pole of the tectum projects via the dorsal optic tract and terminates in the rostral half of the tectum. The bilateral input to the ventrolateral tectum projects via the ventral optic tract and extends the whole length of the tectum. The incidence of direct ipsilateral input to the tectum suggests binocular vision may play a functional role in the survival of this species. In order to test this hypothesis, we examined the retinal distribution of ipsilateral retinal ganglion cells that project to the mediorostral tectum and the size and location of the binocular visual field. Cell distribution was examined by retrograde labelling with rhodamine-conjugated dextran amine delivered by microinjections into the mediorostral pole of the right optic tectum. In the ipsilateral retina, ganglion cells are distributed in a narrow temporoventral area with a mean of 0.44±0.14 x 10³ cells per mm² apposing the retinal margin. In the contralateral retina, ganglion cells are also distributed within this temporoventral region with a mean peak density of 2.33 ± 0.47 x 10³ cells per mm². Three broad classes of ipsilaterally projecting retinal ganglion cells (orthotopic cells within the ganglion cell layer, displaced cells within the inner nuclear layer, and giant cells within the ganglion and inner nuclear layers) are identified, intermingled in both the ipsilateral and contralateral retinae after retrograde labelling from the mediorostral pole of the tectum. Ophthalmoscopic mapping of the monocular and binocular visual fields reveals two small frontal wedges of binocular overlap. A dorsal wedge (12° wide) extends from approximately 7° above the horizontal axis to 10° beyond the vertical axis, and a ventral wedge (20° wide) extends approximately 10° below the horizontal axis to 15° beyond the vertical axis. The dorsal binocular visual field is subtended by the temporoventral region of the retina possessing both ipsilaterally and contralaterally projecting ganglion cells which terminate in the mediorostral pole of the optic tectum. Therefore, the partial decussation of retinal ganglion cell axons at the optic chiasm brings information from corresponding regions of the binocular visual field into register in the mediorostral pole of the optic tectum. In addition, the size of the binocular visual field matches the relative proportion of the retina containing ipsilaterally projecting ganglion cells. The ontogeny and phylogeny of ipsilateral retinofugal projections in actinopterygians is discussed in relation to the putative secondary pathways mediating binocular vision.