PMID- 17456785 OWN - NLM STAT- MEDLINE DCOM- 20070905 LR - 20191210 IS - 0026-895X (Print) IS - 0026-895X (Linking) VI - 72 IP - 2 DP - 2007 Aug TI - Transcriptional regulation of brain-derived neurotrophic factor in the amygdala during consolidation of fear memory. PG - 350-8 AB - We have demonstrated previously that brain-derived neurotrophic factor (BDNF) signaling in the amygdala is required for the consolidation of fear memory. This study is designed to characterize the signal cascades by which fear conditioning modulates transcriptional and translational expression of BDNF. Real-time reverse transcription-coupled polymerase chain reaction showed a significant increase in BDNF exon I- and III-containing mRNA in the amygdala of fear-conditioned rats, indicating that fear conditioning was capable of up-regulating BDNF mRNA. Bilateral administration of actinomycin D or anisomycin to the amygdala attenuated conditioning-induced increase in BDNF protein. Inhibitors for N-methyl-d-aspartate (NMDA) receptor, L-type voltage-dependent calcium channel (L-VDCC), adenylyl cyclase, cAMP-dependent protein kinase (PKA), and calcium/calmodulin-dependent kinase IV (CaMKIV) significantly reduced the increase. Moreover, DNA affinity precipitation and chromatin immunoprecipitation assays showed that phosphorylated cAMP response element-binding protein (p-CREB) binding activity in the proximal region of BDNF promoter I and III was significantly increased after fear conditioning. Intra-amygdala administration of cAMP response element decoy DNA before training impaired fear learning. Taken together, these results suggest that calcium influx through NMDA receptors and L-VDCCs during fear conditioning activates PKA and CaMKIV resulting in CREB phosphorylation. The phosphorylated CREB binds to BDNF promoter and up-regulates the expression of BDNF in the amygdala, which helps the consolidation of fear memory. FAU - Ou, Li-Chin AU - Ou LC AD - Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan. FAU - Gean, Po-Wu AU - Gean PW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070424 PL - United States TA - Mol Pharmacol JT - Molecular pharmacology JID - 0035623 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium Channels, L-Type) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Amygdala/*metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics MH - Calcium Channels, L-Type/physiology MH - Conditioning, Psychological MH - *Fear MH - Male MH - *Memory MH - Promoter Regions, Genetic MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/physiology MH - Signal Transduction MH - *Transcription, Genetic EDAT- 2007/04/26 09:00 MHDA- 2007/09/06 09:00 CRDT- 2007/04/26 09:00 PHST- 2007/04/26 09:00 [pubmed] PHST- 2007/09/06 09:00 [medline] PHST- 2007/04/26 09:00 [entrez] AID - mol.107.034934 [pii] AID - 10.1124/mol.107.034934 [doi] PST - ppublish SO - Mol Pharmacol. 2007 Aug;72(2):350-8. doi: 10.1124/mol.107.034934. Epub 2007 Apr 24.