The IL-33-IL1RL1 signaling axis coordinates remodeling and integration of adult-born neurons in the hippocampus
Phi T. Nguyen1,2, Hiromi Nakao-Inoue1, Ilia D. Vainchtein1, and Anna V. Molofsky1 1Departments of Psychiatry/Weill Institute for Neurosciences and 2Biomedical Sciences Graduate Program, University of California - San Francisco, San Francisco, CA, USA
Learning, memory, and neural circuit plasticity requires continual remodeling of dendrites and synapses. In the mammalian brain, the dentate gyrus of the hippocampus is one of the few germinal niches that undergoes neurogenesis and dynamic circuit remodeling in response to novel experience throughout adulthood. In order to survive and contribute to hippocampal function, adult-born neurons must properly integrate into the local circuitry. However, the mechanisms that underlie this process are poorly understood. Here we show that the IL-1 family cytokine IL-33, which signals through its cognate receptor IL1RL1, is a signaling molecule highly enriched in the dentate gyrus that is required to maintain dendritic spine density and survival of adult-born neurons, consistent with a role in circuit integration. Microglia have been shown to participate in modulating synaptic plasticity and our group has previously shown that IL-33-IL1RL1 signaling promotes microglia engulfment in other CNS regions. In the hippocampus, we also find that the IL-33 receptor IL1RL1 is predominately expressed by microglia and loss of this receptor disrupts microglia ramification and coverage area. We propose that IL-33-IL1RL1 signaling facilitates microglial-mediated synapse and dendritic remodeling in the hippocampus. Future work aims to elucidate the mechanisms and functional implications of this pathway in hippocampal circuit plasticity.
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