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1 Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK
Expression of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) in the CA1 region of the hippocampus can be divided into an early (12 h), protein synthesis-independent phase and a late (>4 h), protein synthesis-dependent phase. In this study we have addressed whether the de novo protein synthesis required for the expression of late-LTP can be sustained solely from the translation of mRNAs located in the dendrites of CA1 pyramidal neurones. Our results show that late-LTP, lasting at least 5 h, can be maintained in hippocampal slices where the dendrites located in stratum radiatum have been isolated from their cell bodies by a microsurgical cut. The magnitude of the potentiation of the slope of field EPSPs in these isolated slices was similar to that recorded in intact slices. Incubation of the slices with the mRNA translation inhibitor cycloheximide or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blocked late-LTP in both intact and isolated slice preparations. In contrast, incubation of slices with the transcription inhibitor, actinomycin D, resulted in a reduction of sustained potentiation, at 4 h, in intact slices while in isolated slices the magnitude of potentiation was similar to that seen in untreated slices. These results indicate that late-LTP can be induced and maintained in isolated dendritic preparations via translation of pre-existing mRNAs.
(Received 29 June 2005;
accepted after revision 15 August 2005;
first published online 18 August 2005)
Corresponding authors K. S Dickson and D. J A Wyllie: Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. Email: kris.dickson{at}ed.ac.uk and dwyllie1{at}staffmail.ed.ac.uk
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