2026-04-19T23:53:12Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2287172026-04-09T05:41:44Zcom_2072_1057col_2072_478916col_2072_478929

00925njm 22002777a 4500 dc López Murcia, Francisco José author Krueger-Burg, Dilja author Wenger, Sally author López Hernández, Tania author Lipstein, Noa author Taschenberger, Holger author Brose, Nils author 2026-04-08T10:21:08Z 2026-04-08T10:21:08Z 2026-02-19 2026-04-08T10:21:08Z Hippocampal mossy fiber (hMF) to CA3 pyramidal cell synapses are thought to support the formation of working memory through presynaptic short-term facilitation (STF) and post-tetanic potentiation (PTP). However, the molecular mechanisms underlying these transient forms of synaptic enhancement are unclear. We show here that Munc13-1-mediated priming of synaptic vesicles (SVs) at active zones controls hMF STF and PTP in response to Ca2+-phospholipid and Ca2+-calmodulin (CaM) signaling. Knock-in mice expressing Munc13-1 variants insensitive to either signaling pathway exhibit pronounced deficits in STF and PTP, and the PTP-induction threshold is markedly increased upon block of Ca2+-phospholipid-Munc13-1 signaling. Since these synaptic defects are accompanied by working memory deficits, especially in mice expressing the Ca2+-phospholipid-insensitive Munc13-1 variant, we conclude that the Ca2+-dependent regulation of Munc13-1-mediated SV priming co-determines hMF short-term plasticity and working memory formation. https://hdl.handle.net/2445/228717 Antagonistes del calci Sinapsi Regulació cel·lular Calcium antagonists Synapses Cellular control mechanisms Ca2+-phospholipid–dependent regulation of Munc13-1 is essential for post-tetanic potentiation at mossy fiber synapses and supports working memory.