Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity.
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 trans-retinoic 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.
Misner
D L
DL
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, Howard Hughes Medical Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jacobs
S
S
Shimizu
Y
Y
de Urquiza
A M
AM
Solomin
L
L
Perlmann
T
T
De Luca
L M
LM
Stevens
C F
CF
Evans
R M
RM
D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D002648:Child; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018632:Mice, Inbred SENCAR; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014801:Vitamin A / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000503:physiopathology*
D018168:Receptors, Retinoic Acid; D014801:Vitamin A