| First Author | Galanis C | Year | 2021 |
| Journal | J Neurosci | Volume | 41 |
| Issue | 24 | Pages | 5157-5172 |
| PubMed ID | 33926999 | Mgi Jnum | J:306668 |
| Mgi Id | MGI:6717287 | Doi | 10.1523/JNEUROSCI.1820-20.2021 |
| Citation | Galanis C, et al. (2021) Amyloid-Beta Mediates Homeostatic Synaptic Plasticity. J Neurosci 41(24):5157-5172 |
| abstractText | 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 APPsalpha in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures prepared from APP (-/-) mice of both sexes. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-beta and not by APPsalpha, and it is neither observed in APP(+/+) tissue treated with beta- or gamma-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca(2+)-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 amyloid-beta levels. |
