Determining the role of NMDARs in retinofugal map formation

In image-forming regions of the visual system, neuronal connections are organized topographically to efficiently relay spatial information. It is well-established that spontaneous activity in the form of retinal waves plays a critical role in the development of topographic maps. However, the mechanisms by which activity mediates map formation remain unclear. Retinal ganglion cells (RGCs) target two image forming regions, the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC), each of which is topographically organized. Previous pharmacological studies suggested that NMDARs play a role in the development of retinofugal topography, but whether NMDARs are required pre-synaptically and/or post-synaptically remains unclear. To directly test the role of pre- and post-synaptic NMDARs in retinofugal map formation, we utilized a conditional genetic strategy to specifically ablate NMDAR function in RGCs (pre-synaptic, Chrnb3-Cre) or in the SC (post-synaptic, En1-Cre). Despite clear ablation of NMDAR function in RGCs, we show that topographic maps developed normally in the dLGN and SC using anatomical tracing methods. Further, we demonstrate that NMDARs are not locally trafficked to the pre-synaptic terminals of RGCs, as assessed via calcium imaging. In contrast, our preliminary data suggests that the termination zones of RGCs in the SC are larger in En1-Cre;NRfl/fl mice compared to littermate controls. Together, these findings suggest that NMDARs expressed by RGCs are not required for retinofugal map formation, while post-synaptic NMDARs expressed by neurons in the SC may be. Future in vivo electrophysiological studies will determine the requirement of post-synaptic NMDARs in establishing functional visual circuits in the SC