PMID- 22761932 OWN - NLM STAT- MEDLINE DCOM- 20130104 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 6 DP - 2012 TI - Learning and nicotine interact to increase CREB phosphorylation at the jnk1 promoter in the hippocampus. PG - e39939 LID - 10.1371/journal.pone.0039939 [doi] LID - e39939 AB - Nicotine is known to enhance long-term hippocampus dependent learning and memory in both rodents and humans via its activity at nicotinic acetylcholinergic receptors (nAChRs). However, the molecular basis for the nicotinic modulation of learning is incompletely understood. Both the mitogen activated protein kinases (MAPKs) and cAMP response element binding protein (CREB) are known to be integral to the consolidation of long-term memory and the disruption of MAPKs and CREB are known to abrogate some of the cognitive effects of nicotine. In addition, the acquisition of contextual fear conditioning in the presence of nicotine is associated with a beta2-subunit containing nAChR-dependent increase in jnk1 (mapk8) transcription in the hippocampus. In the present study, chromatin immunoprecipitation (ChIP) was used to examine whether learning and nicotine interact to alter transcription factor binding or histone acetylation at the jnk1 promoter region. The acquisition of contextual fear conditioning in the presence of nicotine resulted in an increase in phosphorylated CREB (pCREB) binding to the jnk1 promoter in the hippocampus in a beta2-subunit containing nAChR dependent manner, but had no effect on CREB binding; neither fear conditioning alone nor nicotine administration alone altered transcription factor binding to the jnk1 promoter. In addition, there were no changes in histone H3 or H4 acetylation at the jnk1 promoter following fear conditioning in the presence of nicotine. These results suggest that contextual fear learning and nicotine administration act synergistically to produce a unique pattern of protein activation and gene transcription in the hippocampus that is not individually generated by fear conditioning or nicotine administration alone. FAU - Kenney, Justin W AU - Kenney JW AD - Department of Psychology, Temple University, Philadelphia, Pennsylvania, United States of America. FAU - Poole, Rachel L AU - Poole RL FAU - Adoff, Michael D AU - Adoff MD FAU - Logue, Sheree F AU - Logue SF FAU - Gould, Thomas J AU - Gould TJ LA - eng GR - R01 DA024787/DA/NIDA NIH HHS/United States GR - P50 CA143187/CA/NCI NIH HHS/United States GR - DA024787/DA/NIDA NIH HHS/United States GR - T32 DA007237/DA/NIDA NIH HHS/United States GR - DA017949/DA/NIDA NIH HHS/United States GR - R01 DA017949/DA/NIDA NIH HHS/United States GR - DA07237/DA/NIDA NIH HHS/United States GR - CA143187/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120628 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA Primers) RN - 6M3C89ZY6R (Nicotine) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8) SB - IM MH - Base Sequence MH - Chromatin Immunoprecipitation MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - DNA Primers MH - Electrophoresis, Polyacrylamide Gel MH - Fear MH - Hippocampus/*drug effects/metabolism/physiology MH - *Learning MH - Mitogen-Activated Protein Kinase 8/*genetics MH - Nicotine/*pharmacology MH - Phosphorylation MH - Polymerase Chain Reaction MH - *Promoter Regions, Genetic PMC - PMC3386232 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2012/07/05 06:00 MHDA- 2013/01/05 06:00 PMCR- 2012/06/28 CRDT- 2012/07/05 06:00 PHST- 2012/04/02 00:00 [received] PHST- 2012/05/29 00:00 [accepted] PHST- 2012/07/05 06:00 [entrez] PHST- 2012/07/05 06:00 [pubmed] PHST- 2013/01/05 06:00 [medline] PHST- 2012/06/28 00:00 [pmc-release] AID - PONE-D-12-09185 [pii] AID - 10.1371/journal.pone.0039939 [doi] PST - ppublish SO - PLoS One. 2012;7(6):e39939. doi: 10.1371/journal.pone.0039939. Epub 2012 Jun 28.