RIM1/2 in retinal ganglion cells are required for the refinement of ipsilateral axons and eye-specific segregation

Abstract

Neural activity is crucial for the refinement of neuronal connections during development, but the contribution of synaptic release mechanisms is not known. In the mammalian retina, spontaneous neural activity controls the refinement of retinal projections to the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) to form appropriate topographic and eye-specific maps. To evaluate the role of synaptic release, the rab-interacting molecules (RIMs), a family of active zone proteins that play a central role in calcium-triggered release, were conditionally ablated in a subset of retinal ganglion cells (RGCs). We found that this deletion is sufficient to reduce presynaptic release probability onto dLGN neurons. Furthermore, eye-specific segregation in the dLGN and topographic refinement of ipsilateral axons in the SC and the dLGN, are impaired in RIM1/2 conditional knock-out (Rim-cDKO) mice. These defects are similar to those found when retinal activity is globally disturbed. However, reduction in synaptic release had no effect on eye-specific lamination in the SC nor on the retinotopic refinement of contralateral axons in the SC. This study highlights a potential distinction between synaptic and non-synaptic roles of neuronal activity for different mapping rules operating in visual system development.

Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice

“…In the CasRx-treated NMDA-injured retina, we observed a large amount of tdTomato + axons in the treated retina and the optic nerve, but no such axons in control AAV-treated group (Figures 4B and 4C). Remarkably, we found tdTomato + axons in the dLGN and SC, which were much more abundant in the contralateral than the ipsilateral side of the brain (Figures 4D and 4E), consistent with expectation that newly formed axon projections of the converted RGCs correctly send their projections to their central target areas (Assali et al, 2017;Rebsam et al, 2009).…”

Transcriptional logic of cell fate specification and axon guidance in early born retinal neurons revealed by single-cell mRNA profiling

“…Among these genes, we found Pcdh9 (Martersteck et al, 2017), Slc6a4 (Koch et al, 2011) and Prdm16 (Groman-Lupa et al, 2017). Their expression may be more restricted later on during RGC development (Pcdh9), or expand to other RGC cell types (Slc6a4; (Assali et al, 2017)). This latter gene is specific to the RGCs that will send their axon to the ipsilateral side of the brain (Koch et al, 2011;Peng et al, 2018).…”

Twenty-Seven Tamoxifen-Inducible iCre-Driver Mouse Strains for Eye and Brain, Including Seventeen Carrying a New Inducible-First Constitutive-Ready Allele

“…In the developing retina, ISH studies have demonstrated that SLC6A4 is transcribed transiently in retinal ganglion cells (Upton et al 1999; García-Frigola and Herrera 2010). Furthermore, a SLC6A4 -cre mouse strain showed recombination in retinal ganglion cells (Assali et al 2017). Several diseases are associated with SLC6A4 , including obsessive-compulsive disorder (Sinopoli et al 2017), anxiety (Arias et al 2012), and post-traumatic stress disorder, as well as depression-susceptibility in people experiencing emotional trauma (Kuzelova et al 2010).…”