Previous studies have shown that biochemical changes that occur in the amygdala during fear conditioning in vivo are similar to those occur during long term potentiation (LTP) in vitro. Electrophoretic mobility shift assay of nuclear extracts from startle-potentiated rats showed a selective increase in the amygdala of nuclear factor-κB (NF-κB) DNA binding activity. Supershift experiments further indicated that p65 and p50 subunits but not c-Rel were involved in DNA binding. The protein levels of IκB-α were reduced by treatments that reliably induced LTP in this area of the brain. This was accompanied by a decrease of NF-κB in the cytoplasm concomitant with an increase in the nucleus. Quantitative analysis of IκB kinase activity demonstrated that fear training led to an increase in kinase activity, and this effect was inhibited by thalidomide. Paralleled behavioral tests revealed that thalidomide inhibited fear-potentiated startle. Intra-amygdala administration of κB decoy DNA prior to training impaired fear-potentiated startle as well as LTP induction. Similarly, NF-κB inhibitors blocked IκB-α degradation and startle response. These results provide the first evidence of a requirement of NF-κB activation in the amygdala for consolidation of fear memory.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology