Transcriptional regulation of brain-derived neurotrophic factor in the amygdala during consolidation of fear memory

Li Chin Ou, Po-Wu Gean

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalMolecular Pharmacology
Volume72
Issue number2
DOIs
Publication statusPublished - 2007 Aug 1

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Brain-Derived Neurotrophic Factor
Amygdala
Fear
N-Methyl-D-Aspartate Receptors
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Anisomycin
Cyclic AMP Response Element-Binding Protein
L-Type Calcium Channels
Calcium-Calmodulin-Dependent Protein Kinases
Messenger RNA
Memory Consolidation
Chromatin Immunoprecipitation
DNA
Nerve Growth Factors
Response Elements
Dactinomycin
Calcium Channels
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Protein Binding

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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abstract = "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.",
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Transcriptional regulation of brain-derived neurotrophic factor in the amygdala during consolidation of fear memory. / Ou, Li Chin; Gean, Po-Wu.

In: Molecular Pharmacology, Vol. 72, No. 2, 01.08.2007, p. 350-358.

Research output: Contribution to journalArticle

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