A requirement of nuclear factor-kappaB activation in fear-potentiated startle.

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-kappaB (NF-kappaB) 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 IkappaB-alpha were reduced by treatments that reliably induced LTP in this area of the brain. This was accompanied by a decrease of NF-kappaB in the cytoplasm concomitant with an increase in the nucleus. Quantitative analysis of IkappaB 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 kappaB decoy DNA prior to training impaired fear-potentiated startle as well as LTP induction. Similarly, NF-kappaB inhibitors blocked IkappaB-alpha degradation and startle response. These results provide the first evidence of a requirement of NF-kappaB activation in the amygdala for consolidation of fear memory.