NF-kappaB activity in distinct neural subtypes of the rat hippocampus: Influence of time and GABA antagonism in acute slice preparations.
Hippocampal memory-associated synaptic plasticity is driven by a cascade of transcription and new protein synthesis. In vitro electrophysiological studies on acute hippocampal slices have elucidated much of what we know about this molecular cascade. Curiously, these slices require a period of "equilibration" for the recovery of electrophysiological properties such as LTP, implying ongoing time-dependent molecular events necessary for full expression of plasticity. Using standard immunofluorescence combined with confocal imaging and a novel data analysis approach, we implicate the transcription factor NF-kappaB in this plasticity-related molecular adaptation during equilibration. Marked differences in basal NF-kappaB activity in distinct cell types of the hippocampus were observed, with the amount of active NF-kappaB increasing throughout the 2-h equilibration period in all cell types. Moreover, distinct hippocampal neuronal subfields exhibit very different responses to the GABA(A) receptor blocker picrotoxin, the presence of which is required to achieve LTP in the dentate gyrus. These findings have implications for the use of acute hippocampal slices to study the effects of compounds that signal through NF-kappaB on synaptic plasticity. Further investigation into the cellular processes that occur during this molecular adaptation may increase our understanding of plasticity-related events common to both LTP and memory formation.
Applied Neurotherapeutics Research Group, UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Graham K
GK
Sheridan
Mark
M
Pickering
Clare
C
Twomey
Paul N
PN
Moynagh
John J
JJ
O'Connor
Keith J
KJ
Murphy
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D039842:Neural Cell Adhesion Molecule L1; D010852:Picrotoxin; D011963:Receptors, GABA-A; D012794:Sialic Acids; D005680:gamma-Aminobutyric Acid; C000606206:Nfkbia protein, rat; C103469:polysialyl neural cell adhesion molecule