PMID- 16732277
OWN - NLM
STAT- MEDLINE
DCOM- 20060905
LR  - 20220309
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 9
IP  - 7
DP  - 2006 Jul
TI  - AMPA receptors regulate transcription of the plasticity-related immediate-early 
      gene Arc.
PG  - 887-95
AB  - Learning and memory depend critically on long-term synaptic plasticity, which 
      requires neuronal gene expression. In the prevailing view, AMPA receptors mediate 
      fast excitatory synaptic transmission and effect short-term plasticity, but they 
      do not directly regulate neuronal gene expression. By studying regulation of Arc, 
      a gene required for long-term plasticity, we uncovered a new role for AMPA 
      receptors in neuronal gene expression. Spontaneous synaptic activity or activity 
      induced by brain-derived neurotrophic factor (BDNF) elicited Arc expression in 
      cultures of rat cortical neurons and in organotypic brain slices. Notably, 
      inhibiting AMPA receptors strongly potentiated activity-dependent Arc expression. 
      We found that AMPA receptors negatively regulate Arc transcription, but not 
      translation or stability, through a mechanism involving a pertussis 
      toxin-sensitive G protein. These results provide insights into the 
      activity-dependent mechanisms of Arc expression and suggest that, in addition to 
      effecting short-term plasticity, AMPA receptors regulate genes involved in 
      long-term plasticity.
FAU - Rao, Vikram R
AU  - Rao VR
AD  - Gladstone Institute of Neurological Disease, University of California, San 
      Francisco, California 94158, USA.
FAU - Pintchovski, Sean A
AU  - Pintchovski SA
FAU - Chin, Jeannie
AU  - Chin J
FAU - Peebles, Carol L
AU  - Peebles CL
FAU - Mitra, Siddhartha
AU  - Mitra S
FAU - Finkbeiner, Steven
AU  - Finkbeiner S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060528
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (GABA Antagonists)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, AMPA)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - SY7Q814VUP (Calcium)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Bicuculline/pharmacology
MH  - Blotting, Northern/methods
MH  - Blotting, Western/methods
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Cytoskeletal Proteins/genetics/*metabolism
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - GABA Antagonists/pharmacology
MH  - Gene Expression/drug effects/*physiology
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization/methods
MH  - In Vitro Techniques
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neuronal Plasticity/drug effects/*genetics
MH  - Neurons/drug effects/physiology
MH  - Rats
MH  - Receptors, AMPA/*physiology
MH  - Transfection/methods
EDAT- 2006/05/30 09:00
MHDA- 2006/09/06 09:00
CRDT- 2006/05/30 09:00
PHST- 2006/02/21 00:00 [received]
PHST- 2006/04/26 00:00 [accepted]
PHST- 2006/05/30 09:00 [pubmed]
PHST- 2006/09/06 09:00 [medline]
PHST- 2006/05/30 09:00 [entrez]
AID - nn1708 [pii]
AID - 10.1038/nn1708 [doi]
PST - ppublish
SO  - Nat Neurosci. 2006 Jul;9(7):887-95. doi: 10.1038/nn1708. Epub 2006 May 28.