PMID- 37649778 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230907 IS - 2753-149X (Electronic) IS - 2753-149X (Linking) VI - 2 DP - 2023 TI - Dynamics and Mechanisms of ERK Activation after Different Protocols that Induce Long-Term Synaptic Facilitation in Aplysia. PG - kvac014 LID - 10.1093/oons/kvac014 [doi] LID - kvac014 AB - Phosphorylation of the MAPK family member extracellular signal-regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its persistence. We examined ERK activation by three protocols that induce long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse - the standard protocol (five 5-min pulses of 5-HT with interstimulus intervals (ISIs) of 20 min), the enhanced protocol (five pulses with irregular ISIs, which induces greater and longer-lasting LTF) and the two-pulse protocol (two pulses with ISI 45 min). Immunofluorescence revealed complex ERK activation. The standard and two-pulse protocols immediately increased active, phosphorylated ERK (pERK), which decayed within 5 h. A second wave of increased pERK was detected 18 h post-treatment for all protocols. This late phase was blocked by inhibitors of protein kinase A, TrkB and TGF-beta. These results suggest that complex interactions among kinase pathways and growth factors contribute to the late increase of pERK. ERK activity returned to basal 24 h after the standard or two-pulse protocols, but remained elevated 24 h for the enhanced protocol. This 24-h elevation was also dependent on PKA and TGF-beta, and partly on TrkB. These results begin to characterize long-lasting ERK activation, plausibly maintained by positive feedback involving growth factors and PKA, that appears essential to maintain LTF and LTM. Because many processes involved in LTF and late LTP are conserved among Aplysia and mammals, these findings highlight the importance of examining the dynamics of kinase cascades involved in vertebrate long-term memory. CI - (c) The Author(s) 2022. Published by Oxford University Press. FAU - Zhang, Yili AU - Zhang Y AUID- ORCID: 0000-0002-2591-1324 AD - Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, United States. FAU - Liu, Rong-Yu AU - Liu RY AD - Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, United States. FAU - Smolen, Paul AU - Smolen P AD - Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, United States. FAU - Cleary, Leonard J AU - Cleary LJ AD - Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, United States. FAU - Byrne, John H AU - Byrne JH AD - Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, United States. LA - eng GR - R01 NS019895/NS/NINDS NIH HHS/United States GR - R37 NS019895/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20221018 PL - England TA - Oxf Open Neurosci JT - Oxford open neuroscience JID - 9918487584406676 PMC - PMC10464504 OTO - NOTNLM OT - Aplysia OT - ERK OT - TGF-beta OT - TrkB OT - computationally designed training protocol OT - long-term facilitation COIS- None declared. EDAT- 2023/08/31 06:42 MHDA- 2023/08/31 06:43 PMCR- 2022/10/18 CRDT- 2023/08/31 04:04 PHST- 2022/08/22 00:00 [received] PHST- 2022/10/05 00:00 [revised] PHST- 2023/08/31 06:43 [medline] PHST- 2023/08/31 06:42 [pubmed] PHST- 2023/08/31 04:04 [entrez] PHST- 2022/10/18 00:00 [pmc-release] AID - kvac014 [pii] AID - 10.1093/oons/kvac014 [doi] PST - epublish SO - Oxf Open Neurosci. 2022 Oct 18;2:kvac014. doi: 10.1093/oons/kvac014. eCollection 2023.