Atypical Retinal Ganglion Cell Function in a Mouse Model of Fragile X Syndrome

The altered function of peripheral sensory neurons is an emerging mechanism for symptoms of autism spectrum disorders. Visual sensitivities are common in autism, but whether differences in the retina might underlie these sensitivities is not well understood. This includes fragile X syndrome (FXS), which is the most common syndromic cause of autism. We explored retinal function in the Fmr1 knock-out mouse model of FXS. We focused on a specific type of retinal neuron homologous with primate ganglion cells, the "sustained On alpha" retinal ganglion cell, which plays roles in contrast sensing and binocular vision in mice. We found that these cells exhibit changes in dendritic structure and dampened responses to light in male Fmr1 knock-out mice. We show that decreased light sensitivity is due to increased inhibitory input and reduced E-I balance. The change in E-I balance supports the maintenance of circuit excitability similar to what has been observed in the cortex. However, this maintenance also reshapes the tuning of this retinal ganglion cell type. These results show that loss of Fmr1 in the mouse retina affects the sensory function of one retinal neuron type. As other retinal cell types also express Fmr1, FXS may affect the tuning of retinal cells more broadly. Our findings suggest that the retina may be relevant for understanding visual function in FXS.