PMID- 19806658
OWN - NLM
STAT- MEDLINE
DCOM- 20110531
LR  - 20240312
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Print)
IS  - 1050-9631 (Linking)
VI  - 20
IP  - 9
DP  - 2010 Sep
TI  - Hippocampal NMDA receptor subunits differentially regulate fear memory formation 
      and neuronal signal propagation.
PG  - 1072-82
LID - 10.1002/hipo.20705 [doi]
AB  - Activation of NMDA receptors (NMDAR) in the hippocampus is essential for the 
      formation of contextual and trace memory. However, the role of individual NMDAR 
      subunits in the molecular mechanisms contributing to these memory processes is 
      not known. Here we demonstrate, using intrahippocampal injection of 
      subunit-selective compounds, that the NR2A-preferring antagonist impaired 
      contextual and trace fear conditioning as well as learning-induced increase of 
      the nuclear protein c-Fos. The NR2B-specific antagonist, on the other hand, 
      selectively blocked trace fear conditioning without affecting c-Fos levels. 
      Studies with cultured primary hippocampal neurons, further showed that synaptic 
      and extrasynaptic NR2A and NR2B differentially regulate the extracellular 
      signal-regulated kinase 1 and 2/mitogen- and stress-activated protein kinase 1 
      (ERK1/2/MSK1)/c-Fos pathway. Activation of the synaptic population of NMDAR 
      induced cytosolic, cytoskeletal, and perinuclear phosphorylation of ERK1/2 
      (pERK1/2). The nuclear propagation of pERK1/2 signals, revealed by upregulation 
      of the downstream nuclear targets pMSK1 and c-Fos, was blocked by a preferential 
      NR2A but not by a specific NR2B antagonist. Conversely, activation of total 
      (synaptic and extrasynaptic) NMDAR engaged receptors with NR2B subunits, and 
      resulted in membrane retention of pERK1/2 without inducing pMSK1 and c-Fos. 
      Stimulation of extrasynaptic NMDAR alone was consistently ineffective at 
      activating ERK signaling. The discrete contribution of synaptic and total NR2A- 
      and NR2B-containing NMDAR to nuclear transmission vs. membrane retention of ERK 
      signaling may underlie their specific roles in the formation of contextual and 
      trace fear memory.
FAU - Gao, Can
AU  - Gao C
AD  - Department of Psychiatry and Behavioral Sciences and The Asher Center for the 
      Study and Treatment of Depressive Disorders, Chicago, Illinois, USA. 
      can-gao@northwestern.edu
FAU - Gill, Martin B
AU  - Gill MB
FAU - Tronson, Natalie C
AU  - Tronson NC
FAU - Guedea, Anita L
AU  - Guedea AL
FAU - Guzman, Yomayra F
AU  - Guzman YF
FAU - Huh, Kyu Hwan
AU  - Huh KH
FAU - Corcoran, Kevin A
AU  - Corcoran KA
FAU - Swanson, Geoffrey T
AU  - Swanson GT
FAU - Radulovic, Jelena
AU  - Radulovic J
LA  - eng
GR  - R01 MH078064/MH/NIMH NIH HHS/United States
GR  - R01 MH078064-02/MH/NIMH NIH HHS/United States
GR  - R01 MH078064-04/MH/NIMH NIH HHS/United States
GR  - MH 078064/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Cell Membrane/enzymology/metabolism/physiology
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/physiology
MH  - Fear/*physiology
MH  - Female
MH  - Hippocampus/cytology/enzymology/*metabolism
MH  - MAP Kinase Signaling System/*physiology
MH  - Male
MH  - Memory/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/cytology/enzymology/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Synaptic Transmission/physiology
PMC - PMC2891656
MID - NIHMS150171
EDAT- 2009/10/07 06:00
MHDA- 2011/06/01 06:00
PMCR- 2011/09/01
CRDT- 2009/10/07 06:00
PHST- 2009/10/07 06:00 [entrez]
PHST- 2009/10/07 06:00 [pubmed]
PHST- 2011/06/01 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - 10.1002/hipo.20705 [doi]
PST - ppublish
SO  - Hippocampus. 2010 Sep;20(9):1072-82. doi: 10.1002/hipo.20705.