PMID- 14739006
OWN - NLM
STAT- MEDLINE
DCOM- 20040413
LR  - 20211203
IS  - 0166-4328 (Print)
IS  - 0166-4328 (Linking)
VI  - 149
IP  - 1
DP  - 2004 Feb 4
TI  - The role of hippocampal signaling cascades in consolidation of fear memory.
PG  - 17-31
AB  - We investigated the involvement of hippocampal protein kinase A (PKA), protein 
      kinase C (PKC), calcium/calmodulin-dependent protein kinases (CaMK II), and 
      mitogen-activated extracellular signal-regulated kinases 1 and 2 (Mek-1/2) in the 
      phosphorylation of their downstream targets extracellular signal-regulated 
      kinases 1 and 2 (Erk-1/2), cAMP-response element-binding protein (CREB), Elk-1, 
      and p90 ribosomal S6 kinase 1 (p90Rsk-1). The role of these processes in memory 
      consolidation of conditioned fear was determined. C57BL/6N mice were injected 
      into the dorsal hippocampus with inhibitors of PKA, PKC, CaMK II, Mek-1/2, or 
      vehicle before training consisting of a single exposure to a context, tone, and 
      footshock. Freezing behavior of mice reflecting fear memory was scored after 
      their re-exposure to the conditioned stimuli. Inhibition of PKA impaired context- 
      and tone-dependent fear conditioning and significantly reduced the 
      phosphorylation of Elk-1, p90Rsk-1, Erk-1/2, and CREB. PKC inhibition also 
      impaired context- and tone-dependent fear conditioning and prevented the 
      phosphorylation of Erk-1/2, Elk-1, and CREB, without affecting p90Rsk-1. 
      Inhibition of CaMK II did not affect fear conditioning and reduced the 
      phosphorylation of Erk-1/2, Elk-1, CREB, and p90Rsk-1 only transiently, whereas 
      Mek-1/2 inhibition was ineffective in all experiments. It was concluded that 
      hippocampal PKA and PKC play crucial roles in one-trial fear conditioning. 
      Erk-1/2, Elk-1, and CREB were identified as common targets of PKA, PKC, and CaMK 
      II during memory consolidation, however, the time window and sequence of their 
      phosphorylation was specific for the individual kinase.
FAU - Ahi, Janak
AU  - Ahi J
AD  - Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental 
      Medicine, 37075, Goettingen, Germany.
FAU - Radulovic, Jelena
AU  - Radulovic J
FAU - Spiess, Joachim
AU  - Spiess J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/metabolism
MH  - Conditioning, Psychological/*physiology
MH  - Cyclic AMP-Dependent Protein Kinases/drug effects/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Fear/*physiology
MH  - Hippocampus/drug effects/*enzymology
MH  - Male
MH  - Memory/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/drug effects/metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/drug effects/metabolism
MH  - Protein Serine-Threonine Kinases/drug effects/*metabolism
MH  - Signal Transduction/drug effects/*physiology
EDAT- 2004/01/24 05:00
MHDA- 2004/04/14 05:00
CRDT- 2004/01/24 05:00
PHST- 2004/01/24 05:00 [pubmed]
PHST- 2004/04/14 05:00 [medline]
PHST- 2004/01/24 05:00 [entrez]
AID - S0166432803002079 [pii]
AID - 10.1016/s0166-4328(03)00207-9 [doi]
PST - ppublish
SO  - Behav Brain Res. 2004 Feb 4;149(1):17-31. doi: 10.1016/s0166-4328(03)00207-9.