Retinal Ganglion Cell Axons Recognize Specific Guidance Cues Present in the Deafferented Adult Rat Superior Colliculus

Abstract

During development, retinal ganglion cell axons establish a topographically ordered projection from the retina to the superior colliculus (SC). The putative guidance activities for retinal axons that operate during embryonic development are not detectable in the normal adult SC. However, these cues reappear upon transection of the optic nerve of adult rats. In the present study, we used a modified version of the "stripe assay," in which membranes from either anterior or posterior SC alternated with laminin stripes. Temporal embryonic retinal axons consistently avoid membranes from embryonic posterior SC, but only rarely from adult deafferented SC. However, they are attracted to membranes from both embryonic and adult deafferented anterior SC. Nasal retinal axons only show a significant preference for membranes from posterior SC after deafferentation. When retinal axons were offered a choice to grow on membranes either from their embryonic or their deafferented target regions, they showed a preference for the deafferented SC. On carpets consisting of laminin and membranes from normal SC (not deafferented) or nontarget regions (inferior colliculus), temporal and nasal axons grow either in a random fashion or show preferences for the laminin stripes.Our modified version of the classic stripe assay shows specific growth preferences of embryonic retinal axons for membrane lanes from their appropriate embryonic or deafferented adult target regions. These findings suggest that the deafferentation of the SC in adult rats triggers the reexpression of specific guidance activities for retinal axons. Those "attractive" guidance cues appear to be differentially expressed in the developing and deafferented SC. Key words: retina; retinotectal system; development; retinal ganglion cell; stripe assay; guiding cuesThe retinotectal projection has been widely used as a model to examine the mechanisms that underlie the formation of precise topographic patterns. During development of the rat visual system, a topographic retinotectal projection is formed: retinal ganglion cell (RGC) axons from the temporal retina project to the anterior (rostral) superior colliculus (SC), whereas nasal retinal axons project to the posterior (caudal) SC. Ventrally and dorsally located RGCs establish a similar projection along the mediolateral axis of the SC. To analyze the role of putative molecules involved in axonal guidance and target recognition, Walter et al. (1987a) developed an in vitro assay (stripe assay). In this assay, retinal axons were grown on carpets, which consist of alternating stripes of membranes derived from anterior and posterior embryonic tectum (Walter et al., 1987a,b).In all tested species (chick, mouse, fish, and rat), temporal retinal axons avoid growing on membrane stripes from the posterior SC, whereas nasal retinal axons did not show a growth preference (Walter et al., 1987a,b;Godement and Bonhoeffer, 1989;Vielmetter and Stuermer, 1989;Roskies and O'Leary, 1994). Using this assay, two different membrane-bound putative guidi...

Reduction of Potassium Currents and Phosphatidylinositol 3-Kinase-Dependent Akt Phosphorylation by Tumor Necrosis Factor-α Rescues Axotomized Retinal Ganglion Cells from Retrograde Cell DeathIn Vivo

“…Fiber tract lesion of the retinocollicular projection in the rat is an established model to investigate secondary neuronal loss in degenerative processes of the mammalian CNS because of its good surgical accessibility and well known kinetics of cell death (Villegas-Perez et al, 1988;Mey and Thanos, 1993;Bähr and Bonhoeffer, 1994;Bähr and Wizenmann, 1996;Klöcker et al, 1997Klöcker et al, , 1998Kermer et al, 1999aKermer et al, , 2000. Transection of the ON induces a delayed death of 80 -90% of RGCs within 14 d, starting around day 4 and reaching a maximum on day 7 after axotomy (Eschweiler and Bähr, 1993;Mansour-Robaey et al, 1994).…”

Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function

“…Knoll et al (2001a) demonstrated a graded expression pattern of ephrinA in the SC of mice before and after lesion of the optic nerve, remarkably similar to the expression patterns found during development, suggesting that topographic guidance information for a successful re-establishment of the retinocollicular projection was available. Interestingly, RGC axons do not exert guidance preferences in response to membranes from adult unlesioned SC, but only in response to membranes from deafferented SC (Wizenmann et al 1993;Bahr and Wizenmann 1996). In normal adult tissue, the repellent activity of ephrinA is blocked by coexpression of EphA receptors in the SC, such that EphA receptors on retinal axons cannot bind the ephrins in the SC membranes.…”

Increased corticofugal plasticity after unilateral cortical lesions combined with neutralization of the IN‐1 antigen in adult rats

“…In the developing CNS specific factors are expressed at the midline that attract or repulse fibers in order to establish the correct pattern. Whether these guidance cues are still expressed in the mature CNS or whether their reexpression is only triggered by a lesion is not yet clear (e.g., in the visual system lesions induce guidance cues; Wizenmann et al, 1993;Bä hr et al, 1996).…”