Vlasits Anna L, Syeda Maria, Wickman Annelise, Guzman Pedro, Schmidt Tiffany M
Department of Neurobiology, Northwestern University, Evanston, IL, USA.
Department of Ophthalmology, University of Illinois, Chicago, IL, USA.
bioRxiv. 2024 Mar 17:2024.03.15.585283. doi: 10.1101/2024.03.15.585283.
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. We explored retinal function in the Fmr1 knockout model of Fragile X syndrome, focusing on a specific type of retinal neuron, the "sustained On alpha" retinal ganglion cell. We found that these cells exhibit changes in dendritic structure and dampened responses to light in the Fmr1 knockout. 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. These results show that loss of Fmr1 in the mouse retina affects sensory function of one retinal neuron type. Our findings suggest that the retina may be relevant for understanding visual function in Fragile X syndrome.
外周感觉神经元功能改变是自闭症谱系障碍症状出现的一种机制。视觉敏感在自闭症中很常见，但视网膜的差异是否是这些敏感的基础尚不清楚。我们在脆性X综合征的Fmr1基因敲除模型中探索了视网膜功能，重点关注一种特定类型的视网膜神经元，即“持续开启α”视网膜神经节细胞。我们发现这些细胞在Fmr1基因敲除小鼠中表现出树突结构变化和对光反应减弱。我们表明，光敏感性降低是由于抑制性输入增加和E-I平衡降低所致。E-I平衡的变化支持维持与皮质中观察到的类似的回路兴奋性。这些结果表明，小鼠视网膜中Fmr1的缺失会影响一种视网膜神经元类型的感觉功能。我们的研究结果表明视网膜可能与理解脆性X综合征的视觉功能有关。
