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The Journal of Neuroscience, July 1, 2002, 22(13):5432-5441
The Role of Extracellular Regulated Kinases I/II in Late-Phase
Long-Term Potentiation
Kobi
Rosenblum,
Marie
Futter,
Karen
Voss,
Muriel
Erent,
Paul A.
Skehel,
Pim
French,
Louis
Obosi,
Matt W.
Jones, and
Tim V. P.
Bliss
Division of Neurophysiology, National Institute for Medical
Research, London NW7 1AA, United Kingdom
Extracellular regulated kinases (ERKI/II), members of the
mitogen-activated protein kinase family, play a role in
long-term memory and long-term potentiation (LTP). ERKI/II is required
for the induction of the early phase of LTP, and we show that it is also required for the late phase of LTP in area CA1 in
vitro, induced by a protocol of brief, repeated 100 Hz trains.
We also show that ERKI/II is necessary for the upregulation of the
proteins encoded by the immediate early genes Zif268 and
Homer after the induction of LTP in the dentate gyrus by
tetanic stimulation of the perforant path in vivo or by
BDNF stimulation of primary cortical cultures. To test whether the
induction of persistent synaptic plasticity by stimuli such as BDNF is
associated with nuclear translocation of ERKI/II, we expressed enhanced
green fluorescent protein (EGFP)-ERKII in PC12 cell lines and primary
cortical cultures. In both preparations, we observed translocation of
EGFP-ERKII from the cytoplasm to the nucleus in cells exposed to
neurotrophic factors. Our results suggest that the induction of late
LTP involves translocation of ERKI/II to the nucleus in which it
activates the transcription of immediate early genes. The ability to
visualize the cellular redistribution of ERKII after induction of
long-term synaptic plasticity may provide a method for visualizing
neuronal circuits underlying information storage in the brain in
vivo.
Key words:
mitogen-activated protein kinase; long-term potentiation; hippocampus; brain-derived neurotrophic factor; Zif268; immediate early genes; enhanced green fluorescent protein
Copyright © 2002 Society for Neuroscience 0270-6474/02/22135432-10$05.00/0
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