Transcription factor NF-kappaB activation after in vivo perforant path LTP in mouse hippocampus.
There is increasing evidence that transcription factors (TFs) play a critical role in maintaining later phases of hippocampal long-term potentiation (LTP). We have been led to study the role in synaptic plasticity of the powerful, yet generally unheralded, NF-kappaB TF because it may serve as both a signaling molecule after its activation at the synapse and then a transcription initiator upon reaching the nucleus. In the present study, we show that LTP activates NF-kappaB in the intact mouse hippocampus. Mice were sacrificed 15 min after one of three treatments: tetanization (high-frequency stimulation [HFS]), low-frequency stimulation (LFS), or no stimulated control animals (CT). In a first study, nuclear NF-kappaB activity from hippocampus was estimated by electrophoretic mobility shift assays (EMSAs). A higher level of hippocampal TF binding to the NF-kappaB recognition element was found in the HFS group compared with LFS or CT. In a second study, NF-kappaB activity was evaluated by immunohistochemistry with a specific antibody that recognizes the activated form of NF-kappaB. This antibody binds to the exposed nuclear location sequence on the p65 subunit of NF-kappaB consequent to its dissociation from the inhibitory IkappaB molecule. In the four subfields of hippocampus examined--granule cell layer, hilus of the dentate gyrus, CA3 and CA1 pyramidal fields of the hippocampal gyrus--the highest levels of activated NF-kappaB, statistically significant in all cases were found after HFS. In certain comparisons, LFS animals also showed significant elevation with respect to CT. These results support the role of NF-kappaB as part of the synaptic signaling and transcriptional regulation mechanism required in long-term plasticity, emphasizing the combinatorial nature of TF function.
Cresap Neuroscience Laboratory, Northwestern University, Evanston, Illinois, USA.
Ramiro
R
Freudenthal
Arturo
A
Romano
Aryeh
A
Routtenberg
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D019580:Perforant Pathway / Q000166:cytology / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D016328:NF-kappa B; D021122:Protein Subunits