Atypical retinal ganglion cell function in a mouse model of Fragile X syndrome

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, which is the most common syndromic cause of autism. We explored retinal function in the Fmr1 knockout mouse model of Fragile X syndrome. 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 knockout 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 maintenance of circuit excitability similar to what has been observed in 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 sensory function of one retinal neuron type. As other retinal cell types also express Fmr1, Fragile X syndrome may affect the tuning of retinal cells more broadly. Our findings suggest that the retina may be relevant for understanding visual function in Fragile X syndrome. Significance statement Atypical sensory processing underlies some symptoms and experiences of people with autism spectrum disorders. These symptoms may include differences in vision, audition and sense of touch. In recent years, evidence has emerged that these differences start with atypical function of neurons in the periphery. However, not much is known about how ASD affects the function of the retina. Here, we explored retinal function in a mouse model of a disease strongly linked to ASD, Fragile X syndrome. Our experiments demonstrate that a cell type in the retina has dampened responses to light in the mouse model of Fragile X syndrome. Our work suggests that atypical processing in the retina may contribute to sensory symptoms in Fragile X syndrome.