title: Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons.
abstract: The roles of protein kinase C and the MAP-kinase extracellular receptor kinase in structural changes associated with long-term potentiation of network activity were examined in cultured hippocampal neurons. A brief exposure to a conditioning medium that favours activation of the N-methyl-d-aspartate receptor caused a rapid and specific increase in staining of neurons for the phosphorylated form of extracellular receptor kinase as well as of cyclic AMP response element binding protein. Exposure of the cultures to the conditioning medium was followed by a protein synthesis-dependent formation of novel dendritic spines. An extracellular receptor kinase antagonist PD98059 blocked the phosphorylated form of extracellular receptor kinase response and the formation of novel spines. A selective protein kinase C agonist, phorbol 12-myristate 13-acetate, caused activation of extracellular receptor kinase and formation of novel spines. The protein kinase C antagonist GF109203x blocked the phosphorylated form of extracellular receptor kinase response and the subsequent spine formation by phorbol 12-myristate 13-acetate. Both the conditioning medium and phorbol 12-myristate 13-acetate caused a delayed increase in mean amplitude of miniature excitatory postsynaptic currents recorded in the hippocampal neurons. These results indicate that activation of extracellular receptor kinase mediates the effect of a conditioning protocol on the formation of dendritic spines. The formation of novel spines was associated with long-term increase in network activity and functional synaptic connectivity among the cultured neurons.
authors.affiliation: Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Goldin
authors.forename: Menahem
authors.initials: M
authors.lastname: Segal
mesh_terms: D051697:Activating Transcription Factor 1; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004268:DNA-Binding Proteins; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D021621:Imaging, Three-Dimensional / Q000295:instrumentation / Q000379:methods; D007150:Immunohistochemistry / Q000295:instrumentation / Q000379:methods; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D011493:Protein Kinase C / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D051697:Activating Transcription Factor 1; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D011810:Quinoxalines; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D014633:Valine