2026-04-20T02:59:07Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/2287172026-04-09T05:41:44Zcom_2072_1057col_2072_478916col_2072_478929
Ca2+-phospholipid–dependent regulation of Munc13-1 is essential for post-tetanic potentiation at mossy fiber synapses and supports working memory.
López Murcia, Francisco José
Krueger-Burg, Dilja
Wenger, Sally
López Hernández, Tania
Lipstein, Noa
Taschenberger, Holger
Brose, Nils
Antagonistes del calci
Sinapsi
Regulació cel·lular
Calcium antagonists
Synapses
Cellular control mechanisms
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.
2026-04-09T05:41:43Z
2026-04-09T05:41:43Z
2026-04-08T10:21:08Z
2026-04-08T10:21:08Z
2026-02-19
2026-04-08T10:21:08Z
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
https://hdl.handle.net/2445/228717
Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2026.117029
Cell Reports, 2026, vol. 45, num.3, p. 117029
https://doi.org/10.1016/j.celrep.2026.117029
cc-by (c) López-Murcia, F.J. et al., 2026
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Elsevier