Genetic and Cellular Dissection of Experience-Dependent Signaling Driving Critical Period Synaptic Pruning

Abstract

Critical periods are temporally-restricted, early-life time periods when sensory experience remodels brain synaptic connectivity to optimize environmental input. I discovered glial projections infiltrate brain neuropil in response to critical period olfactory sensory experiences, and use the Draper-Basket-Cheerio (human MEGF10-JNK-FLNA) pathway to prune targeted synapses. Additionally, intercellular neuron-to-glia signaling directs glial phagocyte recruitment for the brain synapse elimination mechanism. I discovered that glial insulin receptor signaling directs glial infiltration into the brain neuropil, and that critical period olfactory sensory experience causes phosphatidylserine (PS) externalization signaling to direct glial phagocytosis for synapse pruning.