Subfield-specific immediate early gene expression associated with hippocampal long-term potentiation in vivo.
It is not known whether NMDA receptor-dependent long-term potentiation (LTP) is mediated by similar molecular mechanisms in different hippocampal areas. To address this question we have investigated changes in immediate early gene and protein expression in two hippocampal subfields following the induction of LTP in vivo and in vitro. In granule cells of the dentate gyrus, LTP induced in vivo by tetanic stimulation of the perforant path was followed by strong induction of the immediate early genes (IEGs) Zif268, Arc and Homer. The increase in Zif268 mRNA was accompanied by an increase in protein expression. In contrast, we were unable to detect modulation of the IEGs Zif268, Arc, Homer and HB-GAM following induction of LTP by high-frequency stimulation of the commissural projection to CA1 pyramidal cells in vivo. In this pathway, we also failed to detect modulation of Zif268 protein levels. Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock-induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli. When LTP was induced in vitro neither CA1 pyramidal cells nor granule cells showed an increase in Zif268, Arc or Homer mRNA. However, in the slice preparation, granule cells have a different transcriptional state as basal IEG levels are elevated. These results establish the existence of subfield-specific transcriptional responses to LTP-inducing stimulation in the hippocampus of the intact animal, and demonstrate that in area CA1-enhanced transcription of Zif268, Arc and Homer is not required for the induction of late LTP.
National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. pfrench@nimr.mrc.ac.uk
P J
PJ
French
V
V
O'Connor
M W
MW
Jones
S
S
Davis
M L
ML
Errington
K
K
Voss
B
B
Truchet
C
C
Wotjak
T
T
Stean
V
V
Doyère
M
M
Maroun
S
S
Laroche
T V
TV
Bliss
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004597:Electroshock / Q000009:adverse effects; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D017874:Immediate-Early Proteins; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D019580:Perforant Pathway / Q000166:cytology / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D000072233:Homer Scaffolding Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C092069:activity regulated cytoskeletal-associated protein