Fiscal Reform: Paying for the Harmonious Society

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 ?2-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 ?2-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

Identification of CREs in the <i>jnk1</i>

<p><b>promoter region.</b> A) Depiction of the <i>jnk1</i> promoter region with an indication of identified CREs. CREs in blue indicate sites conserved between <i>mus musculus</i> and <i>homo sapiens</i> and capitalized letters indicate half-site CREs. Lines labeled jnk1a, jnk1b and jnk1c indicate genomic regions covered by primers used in qPCR. B) Analysis of CREB binding to the <i>jnk1</i> and <i>nra4a2</i> promoters and <i>LINE1</i> in the hippocampus. There was greater binding of CREB to the <i>nr4a2</i> promoter than all other regions examined. The regions covered by the jnk1a and jnk1b primers demonstrate greater CREB binding than <i>LINE1</i>. *−p<0.05 compared to <i>LINE1</i>; † −p<0.05 compared to jnk1a, jnk1b and jnk1c.</p