Source Paper
Epigenetic Regulation of <i>bdnf</i> Gene Transcription in the Consolidation of Fear Memory
Farah D. Lubin, Tania L. Roth, J. David Sweatt
Journal of Neuroscience • 2008
Contextual Fear Conditioning
Objective: To determine the contribution of chromatin remodeling and DNA methylation to learning-induced changes in brain-derived neurotrophic factor (bdnf) gene expression in the adult hippocampus during contextual fear memory consolidation
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Protocol Steps
Contextual Fear Conditioning
Animals undergo contextual fear learning where they learn to associate a context with an aversive stimulus
Note: This learning paradigm induces differential regulation of exon-specific bdnf mRNAs
View evidence from paper
“Contextual fear learning induced differential regulation of exon-specific bdnf mRNAs (I, IV, VI, IX)”
Assessment of bdnf DNA Methylation Changes
Measure changes in bdnf DNA methylation and altered local chromatin structure associated with fear learning
Note: Changes in DNA methylation are associated with learning-induced alterations
View evidence from paper
“associated with changes in bdnf DNA methylation and altered local chromatin structure”
Zebularine Infusion Treatment
Infuse zebularine (DNA methyltransferase inhibitor) to alter bdnf DNA methylation and observe effects on bdnf mRNA levels
Note: Altered DNA methylation is sufficient to drive differential bdnf transcript regulation in hippocampus
View evidence from paper
“Infusions of zebularine (a DNA methyltransferase inhibitor) significantly altered bdnf DNA methylation and triggered changes in exon-specific bdnf mRNA levels”
NMDA Receptor Blockade Treatment
Block NMDA receptors to prevent memory-associated alterations in bdnf DNA methylation and assess effects on memory formation
Note: NMDA receptor blockade prevents altered bdnf gene expression and results in memory formation deficit
View evidence from paper
“NMDA receptor blockade prevented memory-associated alterations in bdnf DNA methylation, resulting in a block of altered bdnf gene expression in hippocampus and a deficit in memory formation”
