Event Details:
Innate immune mechanisms of synapse remodeling during brain development
Anna Molofsky, MD, PHD
Assistant Professor in the Department of Psychiatry at University of California, San Francisco (UCSF)
Host: Michelle Monje
Abstract
Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.
Related papers
[1] Vainchtein ID, Chin G, Cho FS, Kelley KW, Miller JG, Chien EC, Liddelow SA, Nguyen PT, Nakao-Inoue H, Dorman LC, Akil O, Joshita S, Barres BA, Paz JT, Molofsky AB, Molofsky AV. Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development. Science. 2018 Mar 16; 359(6381):1269-1273. doi: 10.1126/science.aal3589.
[2] Poskanzer KE, Molofsky AV. Dynamism of an Astrocyte In Vivo: Perspectives on Identity and Function. Annu Rev Physiol. 2018 Feb 10;80:143-157. doi: 10.1146/annurev-physiol-021317-121125.