Cheadle, L., Tzeng, C. P., Kalish, B. T., Harmin, D. A., Rivera, S., Ling, E., Nagy, M. A., Hrvatin, S., Hu, L., Stroud, H., Burkly, L. C., Chen, C., Greenberg, M. E. (August 2018) Visual Experience-Dependent Expression of Fn14 Is Required for Retinogeniculate Refinement. Neuron, 99 (3). 525-539.e10. ISSN 0896-6273 (Print)0896-6273
Abstract
Sensory experience influences the establishment of neural connectivity through molecular mechanisms that remain unclear. Here, we employ single-nucleus RNA sequencing to investigate the contribution of sensory-driven gene expression to synaptic refinement in the dorsal lateral geniculate nucleus of the thalamus, a region of the brain that processes visual information. We find that visual experience induces the expression of the cytokine receptor Fn14 in excitatory thalamocortical neurons. By combining electrophysiological and structural techniques, we show that Fn14 is dispensable for early phases of refinement mediated by spontaneous activity but that Fn14 is essential for refinement during a later, experience-dependent period of development. Refinement deficits in mice lacking Fn14 are associated with functionally weaker and structurally smaller retinogeniculate inputs, indicating that Fn14 mediates both functional and anatomical rearrangements in response to sensory experience. These findings identify Fn14 as a molecular link between sensory-driven gene expression and vision-sensitive refinement in the brain.
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