title: Activity-dependent rapid local RhoA synthesis is required for hippocampal synaptic plasticity.
abstract: 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.
authors: Graduate College of Biomedical Sciences and.
authors: Victor
authors: V
authors: Briz
authors: Graduate College of Biomedical Sciences and.
authors: Guoqi
authors: G
authors: Zhu
authors: Graduate College of Biomedical Sciences and.
authors: Yubin
authors: Y
authors: Wang
authors: Graduate College of Biomedical Sciences and College of Osteopathic Medicine of the Pacific Western University of Health Sciences, Pomona, California 91766.
authors: Yan
authors: Y
authors: Liu
authors: Graduate College of Biomedical Sciences and.
authors: Mariam
authors: M
authors: Avetisyan
authors: College of Osteopathic Medicine of the Pacific Western University of Health Sciences, Pomona, California 91766.
authors: Xiaoning
authors: X
authors: Bi
authors: Graduate College of Biomedical Sciences and mbaudry@westernu.edu.
authors: Michel
authors: M
authors: Baudry
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D017774:Long-Term Potentiation; D008297:Male; D009928:Organ Specificity; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D011500:Protein Synthesis Inhibitors; D019789:Tetraethylammonium; D002154:Calpain; D020742:rhoA GTP-Binding Protein
keywords: BDNF; LTP; actin cytoskeleton; calpain; dendritic protein synthesis
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