Retinocollicular mapping explained?

Abstract

We review and comment on Grimbert & Cang's (2012) model of the development of topographically ordered maps from the retina to the superior colliculus. This model posits a phase in which arbours are created in zones permitted by Eph and ephrin signalling, followed by a phase in which activity-dependent synaptic plasticity refines the map. We show that it is not possible to generate the arborization probability functions used in Grimbert & Cang's simulations using gradients of Ephs and ephrins and the interaction mechanism that Grimbert & Cang propose in their results. Furthermore, the arborization probabilities we do generate are far less sharp than we imagine truly "permissive" ones would be. It remains to be seen if maps can be generated from the non-permissive arborization probabilities generated from gradients.Keywords visual system; topography; computational modelling; chemoaffinity; retinal waves CommentaryThe extensive experimental and theoretical investigation of the development of topographically ordered maps from the retina to its targets ( Figure 1A) has led to two important theories of map development: molecular signalling and activity-dependent synaptic plasticity (Goodhill & Xu, 2005). In theories of molecular signalling, retinal ganglion cell (RGC) growth cones bear receptors in different densities depending on the location of the RGC soma in the retina, and these receptors are activated by ligands expressed in cells in the superior colliculus (SC) at levels depending on their location. This confers on each RGC a preferred location in the SC, which, depending on the pattern of receptor and ligand expression, is not necessarily its correct topographical position. Activitydependent synaptic plasticity of RGC-SC synapses along with correlated activity in the retina can also, in theory, lead to map formation, though extra cues are needed to ensure the orientation of the map is correct (Willshaw & von der Malsburg, 1976). In both theories other mechanisms, such as competition, may be required for a normal topographic map to form.There is experimental evidence that both molecular signalling and activity-dependent synaptic plasticity are involved in map formation. In support of molecular signalling, the Eph and ephrin families of molecules are expressed in gradients along the axes of the retina and colliculus, and their disruption genetically leads to disrupted maps (Feldheim & O'Leary, 2010;Cang & Feldheim, 2013). In support of activity-dependent synaptic plasticity, correlated activity exists in the retina in the form of retinal waves, and its disruption leads to impaired map precision (Torborg & Feller, 2005). Thus the two theories are complementary and the questions centre around the exact form and role of each mechanism and how they interact.Grimbert & Cang (2012) use a computational model to address the roles of activitydependent synaptic plasticity and molecular signalling in the development of topographically ordered maps from the retina to the SC. In contrast to previous models where mole...

Quantitative assessment of computational models for retinotopic map formation

“…In the Isl2-EphA3 mutant maps, the abnormally high values of EphA in much of the retina have no counterpart in the colliculus, yet all the retina projects to the colliculus. This finding rules out strict Type I models.We excluded the 1D branching model by Yates et al (2004) as we were unable to make a 2D model from the information provided.We also excluded the model of Simpson and Goodhill (2011), as chemoaffinity is represented implicitly by a term describing the distance of an axon from its correct location, and the model by Grimbert and Cang (2012), as no method was given to convert gradients to the probability maps used in their simulations (Sterratt and Hjorth, 2013). …”

“…We also excluded the model of Simpson and Goodhill (2011), as chemoaffinity is represented implicitly by a term describing the distance of an axon from its correct location, and the model by Grimbert and Cang (2012), as no method was given to convert gradients to the probability maps used in their simulations (Sterratt and Hjorth, 2013).…”

Visual Maps Development: Reconsidering the Role of Retinal Efnas and Basic Principle of Map Alignment

“…Such approach revealed to be extraordinarily informative in addressing the mechanism of action of the retinal EphAs because the perturbation of their expression occurred in the RGCs only (cell-specificity) and because the graded expression of EphAs was quantitatively altered, from a smooth to an oscillating gradient (change in periodicity). This approach, and subsequent work using the Isl2-EphA3KI model, yielded crucial findings about the mechanisms of retino-collicular and cortico-collicular mapping which have been impacting both experimental (Brown et al, 2000 ; Reber et al, 2004 ; Triplett et al, 2009 ; Bevins et al, 2011 ; Owens et al, 2015 ) and theoretical neurosciences (Koulakov and Tsigankov, 2004 ; Reber et al, 2004 ; Tsigankov and Koulakov, 2006 , 2010 ; Willshaw, 2006 ; Grimbert and Cang, 2012 ; Sterratt, 2013 ; Sterratt and Hjorth, 2013 ; Hjorth et al, 2015 ; Owens et al, 2015 ). It is now widely acknowledged that competition and relative EphA signaling between RGCs control early steps of retino-collicular map formation.…”

Retinotopic Development, Models of

“…Lighter triangles indicate counter-gradients. Figure adapted from (Sterratt and Hjorth, 2013) with permission from Cambridge University Press.…”