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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>\n                    The earliest synaptic plasticity, called synaptic facilitation, is frequently observed at the beginning of any train of action potentials carrying information in the brain. During consecutive action potentials with short intervals, transmissions influence later ones, often enhancing neurotransmitter release. Facilitation is predicted to be controlled by a high-affinity Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sensor that responds to the presynaptic residual Ca\n                    <jats:sup>2+<\/jats:sup>\n                    after the previous Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx. While synapse strengthening via facilitation has been theoretically proposed to underlie instantaneously formed memory, the lack of experimental procedures to specifically manipulate facilitation has hampered attempts to establish a link from facilitation to memory. Through a genetic dissection of Synaptotagmin 7 (Syt7) in\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    , here we determine Syt7 as the high-affinity Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sensor for synaptic facilitation, showing close correlation from synaptic facilitation to memory. At the highly plastic neuromuscular synapses in\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    embryos, we found that facilitation was achieved by an intramolecular interaction of the two Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -binding domains C2A and C2B of Syt7 via the linker. C2B is responsible for the suppression, i.e., inhibiting fusion of a synaptic vesicle to the plasma membrane. Upon binding residual Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , C2A releases this suppression through the eight-amino acid intramolecular linker between C2A and C2B. Supporting this \u201csuppression-release model,\u201d disrupting either the length of this linker or Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -binding to C2A led to specific defects in facilitation. These mutations also induced defects in memory, assayed by a Pavlovian conditioning scheme using\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    adults. This suggests that the Syt7 function required for facilitation is also required for memory.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2528214123","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:12:31Z","timestamp":1790093551000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Calcium sensing by the C2A domain of Synaptotagmin 7 is required through the linker for both synaptic facilitation and memory"],"prefix":"10.1073","volume":"123","author":[{"given":"Akira","family":"Sakurai","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016bgq349","id-type":"ROR","asserted-by":"publisher"}],"name":"Memory Neurobiology Project, Advanced ICT Research Institute, National Institute of Information and Communications Technology","place":["Kobe 651-2492, 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Sakurai T. Fujii M. Yoshihara Data from \u201cCalcium sensing by C2A domain of Synaptotagmin 7 is required through the linker for both synaptic facilitation and memory.\u201d Mendeley. https:\/\/dx.doi.org\/10.17632\/8xwzrct4g2.1. 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