Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.22.152066v1?rss=1 Authors: Galanis, C., Fellenz, M., Becker, D., Bold, C., Lichtenthaler, S. F., Mueller, U. C., Deller, T., Vlachos, A. Abstract: The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPs in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures of APP-/- mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-{beta} (A{beta} and not by APPs, and it is neither observed in APP+/+ tissue treated with {beta}- or {gamma}-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased A{beta} levels. Copy rights belong to original authors. Visit the link for more info