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

Despite its long history, the central effects of progressive depletion of v itamin A in adult mice has not been previously described. An examination of vitamin-deprived animals revealed a progressive and ultimately profound im pairment of hippocampal CA1 longterm 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 trans -retinoic acid to acute hippocampal slices. We find retinoid responsive tra nsgenes to be highly active in the hippocampus, and by using dissected expl ants, 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 s ynaptic plasticity within the adult brain, and suggest that key genes requi red for long-term potentiation and long-term depression are retinoid depend ent. These data suggest a major mental consequence for the hundreds of mill ions of adults and children who are vitamin A deficient.