PMID- 25653381 OWN - NLM STAT- MEDLINE DCOM- 20150414 LR - 20181113 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 35 IP - 5 DP - 2015 Feb 4 TI - Activity-dependent rapid local RhoA synthesis is required for hippocampal synaptic plasticity. PG - 2269-82 LID - 10.1523/JNEUROSCI.2302-14.2015 [doi] AB - Dendritic protein synthesis and actin cytoskeleton reorganization are important events required for the consolidation of hippocampal LTP and memory. However, the temporal and spatial relationships between these two processes remain unclear. Here, we report that treatment of adult rat hippocampal slices with BDNF or with tetraethylammonium (TEA), which induces a chemical form of LTP, produces a rapid and transient increase in RhoA protein levels. Changes in RhoA were restricted to dendritic spines of CA3 and CA1 and require de novo protein synthesis regulated by mammalian target of rapamycin (mTOR). BDNF-mediated stimulation of RhoA activity, cofilin phosphorylation, and actin polymerization were completely suppressed by protein synthesis inhibitors. Furthermore, intrahippocampal injections of RhoA antisense oligodeoxynucleotides inhibited theta burst stimulation (TBS)-induced RhoA upregulation in dendritic spines and prevented LTP consolidation. Addition of calpain inhibitors after BDNF or TEA treatment maintained RhoA levels elevated and prolonged the effects of BDNF and TEA on actin polymerization. Finally, the use of isoform-selective calpain inhibitors revealed that calpain-2 was involved in RhoA synthesis, whereas calpain-1 mediated RhoA degradation. Overall, this mechanism provides a novel link between dendritic protein synthesis and reorganization of the actin cytoskeleton in hippocampal dendritic spines during LTP consolidation. CI - Copyright (c) 2015 the authors 0270-6474/15/352269-14$15.00/0. FAU - Briz, Victor AU - Briz V AD - Graduate College of Biomedical Sciences and. FAU - Zhu, Guoqi AU - Zhu G AD - Graduate College of Biomedical Sciences and. FAU - Wang, Yubin AU - Wang Y AD - Graduate College of Biomedical Sciences and. FAU - Liu, Yan AU - Liu Y AD - Graduate College of Biomedical Sciences and College of Osteopathic Medicine of the Pacific Western University of Health Sciences, Pomona, California 91766. FAU - Avetisyan, Mariam AU - Avetisyan M AD - Graduate College of Biomedical Sciences and. FAU - Bi, Xiaoning AU - Bi X AD - College of Osteopathic Medicine of the Pacific Western University of Health Sciences, Pomona, California 91766. FAU - Baudry, Michel AU - Baudry M AD - Graduate College of Biomedical Sciences and mbaudry@westernu.edu. LA - eng GR - R15 MH101703/MH/NIMH NIH HHS/United States GR - P01NS045260-01/NS/NINDS NIH HHS/United States GR - P01 NS045260/NS/NINDS NIH HHS/United States GR - R01NS057128/NS/NINDS NIH HHS/United States GR - R01 NS057128/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Actin Depolymerizing Factors) RN - 0 (Actins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Synthesis Inhibitors) RN - 66-40-0 (Tetraethylammonium) RN - EC 3.4.22.- (Calpain) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Actin Cytoskeleton/metabolism MH - Actin Depolymerizing Factors/metabolism MH - Actins/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - CA1 Region, Hippocampal/drug effects/*metabolism/physiology MH - CA3 Region, Hippocampal/drug effects/*metabolism/physiology MH - Calpain/antagonists & inhibitors/metabolism MH - Dendritic Spines/metabolism MH - *Long-Term Potentiation MH - Male MH - Organ Specificity MH - Phosphorylation MH - Protein Synthesis Inhibitors/pharmacology MH - Proteolysis MH - Rats MH - Rats, Sprague-Dawley MH - Tetraethylammonium/pharmacology MH - rhoA GTP-Binding Protein/genetics/*metabolism PMC - PMC4315844 OTO - NOTNLM OT - BDNF OT - LTP OT - actin cytoskeleton OT - calpain OT - dendritic protein synthesis COIS- The authors declare no competing financial interests. EDAT- 2015/02/06 06:00 MHDA- 2015/04/15 06:00 PMCR- 2015/08/04 CRDT- 2015/02/06 06:00 PHST- 2015/02/06 06:00 [entrez] PHST- 2015/02/06 06:00 [pubmed] PHST- 2015/04/15 06:00 [medline] PHST- 2015/08/04 00:00 [pmc-release] AID - 35/5/2269 [pii] AID - 2302-14 [pii] AID - 10.1523/JNEUROSCI.2302-14.2015 [doi] PST - ppublish SO - J Neurosci. 2015 Feb 4;35(5):2269-82. doi: 10.1523/JNEUROSCI.2302-14.2015.