A molecular mechanism for the topographic alignment of convergent neural maps

Abstract

Sensory processing requires proper alignment of neural maps throughout the brain. In the superficial layers of the superior colliculus of the midbrain, converging projections from retinal ganglion cells and neurons in visual cortex must be aligned to form a visuotopic map, but the basic mechanisms mediating this alignment remain elusive. In a new mouse model, ectopic expression of ephrin-A3 (Efna3) in a subset of retinal ganglion cells, quantitatively altering the retinal EFNAs gradient, disrupts cortico-collicular map alignment onto the retino-collicular map, creating a visuotopic mismatch. Genetic inactivation of ectopic EFNA3 restores a wild-type cortico-collicular map. Theoretical analyses using a new mapping algorithm model both map formation and alignment, and recapitulate our experimental observations. The algorithm is based on an initial sensory map, the retino-collicular map, which carries intrinsic topographic information, the retinal EFNAs, to the superior colliculus. These EFNAs subsequently topographically align ingrowing visual cortical axons to the retino-collicular map.DOI: http://dx.doi.org/10.7554/eLife.20470.001

The Mouse Superior Colliculus: An Emerging Model for Studying Circuit Formation and Function

“…A different experiment suggests that EphA/ephrin-A interactions between incoming V1 axons and RGC axons in the SC are also used to align these maps. When ephrin-A3 is ectopically expressed in a subset of RGC axons there is no defect in retinocollicular topography, but the V1–SC map is disrupted in a manner consistent with axonal ephrin-A3 acting as a repellent for incoming V1 axons (Savier et al, 2017 ).…”

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

“…This principle is based on a target-independent axon-axon interaction mechanism between RGCs, originally hypothesized by Bonhoeffer (Bonhoeffer and Huf, 1985 ; Weth et al, 2014 ). In a work recently published (Savier et al, 2017 ) we analyzed visual maps formation and alignment in the SC in Isl2-Efna3KI animals. Similar to the Isl2-EphA3KI model, the Isl2-Efna3KI mouse over-express the Efna3 ligand in 50% of the RGCs only , therefore creating an oscillatory gradient of Efnas in the RGCs (cell-specificity and quantitative perturbation).…”

The mouse cortico-tectal projectome

“…Disruptions in corticotectal projections have been implicated in attention-deficit and autism spectrum disorders [4][5][6][7][8] . Topographic cortico-tectal projections from primary visual, auditory, and motor areas have been well studied; however, the integration of higher-order associative cortical inputs to the SC has not been thoroughly characterized 3,9,10 . The mouse SC is an emergent structural model for the rodent visual system and the circuit formation that facilitates multisensory integration 11 ; thus, it is important to understand the organizational principles of how the confluence of higher-order cortical information is integrated and channeled to downstream motor systems to regulate a diverse repertoire of behaviors.…”