title: Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation.
abstract: Newly synthesized Arc mRNA is selectively targeted to synapses that have experienced particular patterns of activity. Here, we demonstrate that the targeting requires NMDA receptor activation. Arc expression was induced by an electroconvulsive seizure, and the newly synthesized mRNA was then targeted to synaptic sites by activating the perforant path projections to the dentate gyrus. When micropipette electrodes containing NMDA receptor antagonists (MK801 or APV) were positioned in the dentate gyrus during the stimulation period, newly synthesized Arc mRNA was transported into dendrites but did not localize in the activated lamina; instead, the mRNA remained diffusely distributed. AMPA receptor antagonists (CNQX) blocked targeting of Arc mRNA in a small region, and mGluR antagonists (MCPG) did not affect localization. These results demonstrate that NMDA receptor activation is required for the targeting of Arc mRNA to active synapses.
authors.affiliation: Reeve-Irvine Research Center and, Department of Anatomy and Neurobiology, College of Medicine, University of California at Irvine, Irvine, CA 92697, USA. osteward@uci.edu
authors.forename: O
authors.initials: O
authors.lastname: Steward
authors.forename: P F
authors.initials: PF
authors.lastname: Worley
mesh_terms: D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004597:Electroshock / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D019580:Perforant Pathway / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C092069:activity regulated cytoskeletal-associated protein