Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity

D. L. Misner, S. Jacobs, Y. Shimizu, A. M. De Urquiza, L. Solomin, T. Perlmann, L. M. De Luca, C. F. Stevens, R. M. Evans

Research output: Contribution to journalArticlepeer-review

210 Scopus citations


Despite its long history, the central effects of progressive depletion of vitamin A in adult mice has not been previously described. An examination of vitamin-deprived animals revealed a progressive and ultimately profound impairment of hippocampal CA1 long-term potentiation and a virtual abolishment of long-term depression. Importantly, these losses are fully reversible by dietary vitamin A replenishment in vivo or direct application of all transretinoic acid to acute hippocampal slices. We find retinoid responsive transgenes to be highly active in the hippocampus, and by using dissected explants, we show the hippocampus to be a site of robust synthesis of bioactive retinoids. In aggregate, these results demonstrate that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain, and suggest that key genes required for long-term potentiation and long-term depression are retinoid dependent. These data suggest a major mental consequence for the hundreds of millions of adults and children who are vitamin A deficient.

Original languageEnglish (US)
Pages (from-to)11714-11719
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - Sep 25 2001
Externally publishedYes

ASJC Scopus subject areas

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