Reduced Nuclear Factor kappa B activation in dentate gyrus after active avoidance training.

Nuclear Factor kappa B (NF-kappaB) is a transcription factor associated with neuroplasticity and neuronal survival during injury. Although NF-kappaB has been proven to be involved in various processes of repair, there is also evidence that NF-kappaB is associated with learning and memory formation. Our laboratory has previously observed that mice lacking the NF-kappaB p50 subunit are not proficient in learning tasks associated with active avoidance training, an effective learning paradigm. The purpose of this study is to identify changes in NF-kappaB levels after active avoidance training using kappaB-dependent lacZ transgenic mice. Levels of NF-kappaB activity were detected immunohistochemically after active avoidance training in brain regions associated with learning and memory. NF-kappaB activity in trained mice was significantly decreased in the dentate gyrus, but no significant changes were found in other brain regions of trained mice compared to untrained mice. The number of p50-containing neurons was counted in the dentate gyrus and a significant increase was discovered in the trained mice relative to untrained mice. The decrease of NF-kappaB-containing neurons in the dentate gyrus coincides with elevated levels of activated p50 neurons and may be caused by the ability of p50 homodimers to inhibit NF-kappaB transactivation. These results indicate that increased p50 expression down-regulates NF-kappaB activity in the dentate gyrus after exposure to unconditioned stimulus. Therefore, a reduction of NF-kappaB activation and its target genes appears to be a necessary event for early stages of learning and memory consolidation associated with active avoidance training.