Postsynaptic NMDA Receptor Expression Is Required for Visual Corticocollicular Projection Refinement in the Mouse Superior Colliculus

Abstract

Efficient sensory processing of spatial information is facilitated through the organization of neuronal connections into topographic maps of space. In integrative sensory centers, converging topographic maps must be aligned to merge spatially congruent information. The superior colliculus (SC) receives topographically ordered visual inputs from retinal ganglion cells (RGCs) in the eye and layer 5 neurons in the primary visual cortex (L5-V1). Previous studies suggest that RGCs instruct the alignment of later-arriving L5-V1 inputs in an activity-dependent manner. However, the molecular mechanisms underlying this remain unclear. Here, we explored the role of NMDA receptors in visual map alignment in the SC using a conditional genetic knockout approach. We leveraged a novel knock-in mouse line that expresses tamoxifen-inducible Cre recombinase under the control of theTal1gene (Tal1CreERT2), which we show allows for specific recombination in the superficial layers of the SC. We usedTal1CreERT2mice of either sex to conditionally delete the obligate GluN1 subunit of the NMDA receptor (SC-cKO) during the period of visual map alignment. We observed a significant disruption of L5-V1 axon terminal organization in the SC of SC-cKO mice. Importantly, retinocollicular topography was unaffected in this context, suggesting that alignment is also disrupted. Time-course experiments suggest that NMDA receptors may play a critical role in the refinement of L5-V1 inputs in the SC. Together, these data implicate NMDA receptors as critical mediators of activity-dependent visual map alignment in the SC.SIGNIFICANCE STATEMENTAlignment of topographic inputs is critical for integration of spatially congruent sensory information; however, little is known about the mechanisms underlying this complex process. Here, we took a conditional genetic approach to explore the role of NMDA receptors in the alignment of retinal and cortical visual inputs in the superior colliculus. We characterize a novel mouse line providing spatial and temporal control of recombination in the superior colliculus and reveal a critical role for NMDA expression in visual map alignment. These data support a role for neuronal activity in visual map alignment and provide mechanistic insight into this complex developmental process.