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Speaker: Lucas Cheadle, Ph.D.
Title: Sensory experience shapes neural connectivity through cytokine signaling between microglia and neurons
Abstract: Sensory experience shapes the connectivity, plasticity, and function of the brain across the lifespan of an organism. Yet, how the developing brain acquires this incredible ability to interpret and respond to environmental stimuli remains poorly understood. To derive mechanistic insight into the role of experience in brain development, we applied single-cell transcriptomics to the dorsal lateral geniculate nucleus (dLGN) of the thalamus, a brain region that undergoes a critical period of experience-dependent circuit refinement during the first month of postnatal life. This approach revealed that transcription of the gene encoding the cytokine receptor Fn14 is induced in neurons in response to visual experience. Combining molecular, electrophysiological, and ultrastructural strategies, we found that Fn14 and its ligand, the pro-inflammatory cytokine TWEAK, signal together to bidirectionally regulate both the experience-dependent strengthening of synapses and the elimination of synapses that fail to strengthen. Microglia, the resident immune cells of the brain, are the predominant source of TWEAK in the dLGN, and we found that TWEAK transcription is induced in microglia in response to visual experience. These experiments demonstrate that experience-dependent transcription in non-neuronal cells is a critical mechanism through which an organism’s interactions with the environment influence the connectivity of the brain. This work also defines a novel role for microglia in neural circuit development, opening up new avenues for experimentally dissecting the cellular and molecular mechanisms through which sensory experience shapes the developing brain.
Bio: Originally from rural Oklahoma, Dr. Lucas Cheadle graduated from the Oklahoma School of Science and Mathematics in Oklahoma City before attending Smith College in western Massachusetts. At Smith, Dr. Cheadle studied activity-dependent mechanisms of retinal neuron development. Dr. Cheadle obtained his Bachelor’s degree in Neuroscience from Smith in 2005 and joined the Interdepartmental Neuroscience Program at Yale University for his doctoral training in 2008. At Yale, Dr. Cheadle worked with Dr. Thomas Biederer to characterize novel signaling pathways that promote synapse formation between developing neurons. After receiving his Ph.D. in Neuroscience from Yale in 2014, Dr. Cheadle joined the lab of Dr. Michael Greenberg at Harvard Medical School where he adopted the developing visual system as an experimental paradigm to study the roles of sensory experience in shaping brain circuits in vivo. During his postdoctoral work, Dr. Cheadle identified a novel role for microglia, the resident immune cells of the brain, in neural circuit development. Dr. Cheadle currently resides in Boston, Massachusetts and is a citizen of the Chickasaw Nation in southern Oklahoma.