PMID- 38262726 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20240325 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 44 IP - 9 DP - 2024 Feb 28 TI - Synaptotagmin 7 Sculpts Short-Term Plasticity at a High Probability Synapse. LID - 10.1523/JNEUROSCI.1756-23.2023 [doi] LID - e1756232023 AB - Synapses with high release probability (P(r) ) tend to exhibit short-term synaptic depression. According to the prevailing model, this reflects the temporary depletion of release-ready vesicles after an initial action potential (AP). At the high-P(r) layer 4 to layer 2/3 (L4-L2/3) synapse in rodent somatosensory cortex, short-term plasticity appears to contradict the depletion model: depression is absent at interstimulus intervals (ISIs) <50 ms and develops to a maximum at approximately 200 ms. To understand the mechanism(s) underlying the biphasic time course of short-term plasticity at this synapse, we used whole-cell electrophysiology and two-photon calcium imaging in acute slices from male and female juvenile mice. We tested several candidate mechanisms including neuromodulation, postsynaptic receptor desensitization, and use-dependent changes in presynaptic AP-evoked calcium. We found that, at single L4-L2/3 synapses, P(r) varies as a function of ISI, giving rise to the distinctive short-term plasticity time course. Furthermore, the higher-than-expected P(r) at short ISIs depends on expression of synaptotagmin 7 (Syt7). Our results show that two distinct vesicle release processes summate to give rise to short-term plasticity at this synapse: (1) a basal, high-P(r) release mechanism that undergoes rapid depression and recovers slowly (tau = approximately 3 s) and (2) a Syt7-dependent mechanism that leads to a transient increase in P(r) (tau = approximately 100 ms) after the initial AP. We thus reveal how these synapses can maintain a very high probability of neurotransmission for multiple APs within a short time frame. Key words : depression; facilitation; short-term plasticity; synaptotagmin 7. CI - Copyright (c) 2024 Chiu and Carter. FAU - Chiu, Delia N AU - Chiu DN AUID- ORCID: 0000-0002-7343-7962 AD - European Neuroscience Institute Gottingen - A Joint Initiative of the University Medical Center Gottingen and the Max Planck Society, 37077 Gottingen, Germany. FAU - Carter, Brett C AU - Carter BC AUID- ORCID: 0000-0001-6474-6571 AD - European Neuroscience Institute Gottingen - A Joint Initiative of the University Medical Center Gottingen and the Max Planck Society, 37077 Gottingen, Germany b.carter@eni-g.de. LA - eng PT - Journal Article DEP - 20240228 PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - SY7Q814VUP (Calcium) RN - 134193-27-4 (Synaptotagmins) RN - 0 (Syt7 protein, mouse) SB - IM MH - Animals MH - Female MH - Male MH - Mice MH - *Calcium/metabolism MH - *Neuronal Plasticity/physiology MH - Synapses/physiology MH - Synaptic Transmission/physiology MH - Synaptotagmins/genetics/metabolism PMC - PMC10904093 COIS- The authors declare no competing financial interests. EDAT- 2024/01/24 00:42 MHDA- 2024/03/01 06:44 PMCR- 2024/02/28 CRDT- 2024/01/23 21:13 PHST- 2023/09/20 00:00 [received] PHST- 2023/11/20 00:00 [revised] PHST- 2023/12/15 00:00 [accepted] PHST- 2024/03/01 06:44 [medline] PHST- 2024/01/24 00:42 [pubmed] PHST- 2024/01/23 21:13 [entrez] PHST- 2024/02/28 00:00 [pmc-release] AID - JNEUROSCI.1756-23.2023 [pii] AID - JN-RM-1756-23 [pii] AID - 10.1523/JNEUROSCI.1756-23.2023 [doi] PST - epublish SO - J Neurosci. 2024 Feb 28;44(9):e1756232023. doi: 10.1523/JNEUROSCI.1756-23.2023.