Journal
NATURE NEUROSCIENCE
Volume 13, Issue 9, Pages 1082-U73Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2611
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Funding
- US Public Health Service (NIH) [R37 MH51106, P50 MH084020, 5K12 NS001696-07]
- National Basic Research Program of China [2004CB518800]
- Science Fund for Creative Research Group, China
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It has been suggested that gene expression and protein synthesis are required for both long-term memory consolidation and late phases of long-term potentiation and long-term depression (LTD). The necessary genes and the specific transcription factor binding sites in their promoters remain unknown. We found that inhibition of the transcription factor SRF or its cofactor MAL blocked the late phase of LTD in mouse cultured cerebellar Purkinje cells, as did deletion of the immediate early gene Arc. Using neuronal bacterial artificial chromosome (BAC) transfection, we found that, in Arc(-/-) cells transfected with a wild-type Arc BAC, late-phase LTD was rescued. However, mutation of one SRF-binding site in the Arc promoter (SRE 6.9RF engineered to bind mutated SRE 6.9 restored late-phase LTD in Arc(-/-), S) blocked this rescue. Co-transfection of wild-type Arc and SRE 6.9 mutant BAC cells. Thus, SRF binding to SRE 6.9 in the Arc promoter is required for the late phase of cerebellar LTD.
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