NMDA Receptor Expression by Retinal Ganglion Cells Is Not Required for Retinofugal Map Formation nor Eye-Specific Segregation in the Mouse

Abstract

Retinal ganglion cells (RGCs) project topographically to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN). Spontaneous activity plays a critical role in retinotopic mapping in both regions; however, the molecular mechanisms underlying activity-dependent refinement remain unclear. Previous pharmacologic studies implicate NMDA receptors (NMDARs) in the establishment of retinotopy. In other brain regions, NMDARs are expressed on both the pre-and post-synaptic side of the synapse, and recent work suggests that pre-synaptic and post-synaptic NMDARs play distinct roles in retinotectal developmental dynamics. To directly test the role of NMDARs expressed by RGCs in retinofugal map formation, we took a conditional genetic knockout approach to delete the obligate GluN1 subunit of NMDARs in RGCs. Here, we demonstrate reduced GluN1 expression in the retina of Chrnb3-Cre;GluN1 flox/flox (pre-cKO) mice without altered expression in the SC. Anatomical tracing experiments revealed no significant changes in termination zone size in the SC and dLGN of pre-cKO mice, suggesting NMDAR function in RGCs is not an absolute requirement for topographic refinement. Further, we observed no change in the eye-specific organization of retinal inputs to the SC nor dLGN. To verify that NMDA induces activity in RGC terminals, we restricted GCaMP5 expression to RGCs and confirmed induction of calcium transients in RGC terminals. Together, these findings demonstrate that NMDARs expressed by RGCs are not required for retinofugal topographic map formation nor eye-specific segregation in the mouse. 4 Significance StatementTopographic organization of retinal inputs in the brain is thought to be critical for the efficient relay of spatial information in the visual scene. Previous studies suggest NMDARs play a crucial role in establishing topography in the superior colliculus; however, these studies could not distinguish between potential pre-or post-synaptic roles. Here, we show NMDAR function in retinal ganglion cells (RGCs) is not required for the establishment of topography. Further, we find RGC NMDARs are not required to establish or maintain eye-specific laminae in retinorecipient regions.