Assessment of the role of MAP kinase in mediating activity-dependent transcriptional activation of the immediate early gene Arc/Arg3.1 in the dentate gyrus in vivo.
Different physiological and behavioral events activate transcription of Arc/Arg3.1 in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of Arc/Arg3.1 transcription in dentate granule cells in vivo and activation of mitogen-activated protein (MAP) kinase as measured by extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation. We show that ERK1/2 phosphorylation is strongly induced in dentate granule cells within minutes after induction of perforant path long-term potentiation (LTP). Phospho-ERK staining appears in nuclei within minutes after stimulation commences, and ERK phosphorylation returns to control levels within 60 min. Electroconvulsive seizures, which strongly induce prolonged Arc/Arg3.1 transcription in dentate granule cells, induced ERK1/2 phosphorylation in granule cells that returned to control levels within 30 min. Following 30, 60, and 120 min of exploration in a novel complex environment, Arc/Arg3.1 transcription was activated in many more granule cells than stained positively for p-ERK at all time points. Although Arc/Arg3.1 transcription was induced in most pyramidal neurons in CA1 following exploration, very few pyramidal neurons exhibited nuclear p-ERK1/2 staining. Local delivery of U0126 during the induction of perforant path LTP blocked transcriptional activation of Arc/Arg3.1 in a small region near the injection site and blocked Arc/Arg3.1 protein expression over a wider region. Our results indicate that activation of Arc/Arg3.1 transcription in dentate granule cells in vivo is mediated in part by MAP kinase activation, but other signaling pathways also contribute, especially in the case of Arc/Arg3.1 induction in response to experience.
Department of Anatomy and Neurobiology, Reeve-Irvine Research Center, University of California at Irvine, Irvine, California 92697, USA.
Jennifer K
JK
Chotiner
Jessica
J
Nielson
Shannon
S
Farris
Gail
G
Lewandowski
Fen
F
Huang
Karla
K
Banos
Ray
R
de Leon
Oswald
O
Steward
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000502:physiology; D018891:Dentate Gyrus / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D005260:Female; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation / Q000502:physiology*
D002070:Butadienes; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009570:Nitriles; C113580:U 0126; C092069:activity regulated cytoskeletal-associated protein; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases