title: Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains.
abstract: Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6) locally near active synapses. Using antibodies specific for phosphorylation at different sites (ser235/236 versus ser240/244), we show that strong synaptic activation led to dramatic increases in immunostaining throughout postsynaptic neurons with selectively higher staining for p-ser235/236 in the activated dendritic lamina. Following LTP induction, phosphorylation at ser235/236 was detectable by 5 min, peaked at 30 min, and was maintained for hours. Phosphorylation at both sites was completely blocked by local infusion of the NMDA receptor antagonist, APV. Despite robust induction of p-rpS6 following high frequency stimulation, assessment of protein synthesis by autoradiography revealed no detectable increases. Exploration of a novel environment led to increases in the number of p-rpS6-positive neurons throughout the forebrain in a pattern reminiscent of immediate early gene induction and many individual neurons that were p-rpS6-positive coexpressed Arc protein. Our results constrain hypotheses about the possible role of rpS6 phosphorylation in regulating postsynaptic protein synthesis during induction of synaptic plasticity.
authors.affiliation: Reeve-Irvine Research Center, Center for the Neurobiology of Learning and Memory Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory.
authors.forename: Patricia Salgado
authors.initials: PS
authors.lastname: Pirbhoy
authors.affiliation: Reeve-Irvine Research Center, Center for the Neurobiology of Learning and Memory Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA.
authors.forename: Shannon
authors.identifier: 0000-0003-4473-1684
authors.initials: S
authors.lastname: Farris
authors.affiliation: Reeve-Irvine Research Center, Center for the Neurobiology of Learning and Memory Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA Department of Neurosurgery, University of California, Irvine, California 92697, USA osteward@uci.edu.
authors.forename: Oswald
authors.identifier: 0000-0001-7069-8756
authors.initials: O
authors.lastname: Steward
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D005106:Exploratory Behavior; D005260:Female; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D038601:Ribosomal Protein S6