Significance of vitamin A to brain function, behavior and learning

Abstract

Retinoid acid, the bioactive metabolite of vitamin A, is a potent signaling molecule in the brains of growing and adult animals, regulates numerous gene products, and modulates neurogenesis, neuronal survival and synaptic plasticity. Vitamin A deficiency (VAD) is a global health problem, yet our knowledge of its effects on behavior and learning is still emerging. Here we review studies that have implicated retinoids in learning and memory deficits of post-embryonic and adult rodent and songbird models. Dietary vitamin A supplementation improves learning and memory in VAD rodents and can ameliorate cognitive declines associated with normal aging. Songbird studies examine the effects of retinoid signaling on vocal/auditory learning and are uniquely suited to study the behavioral effects of VAD because the neural circuitry of the song system is discrete and well understood. Similar to human speech acquisition, avian vocal learning proceeds in well-defined stages of template acquisition, rendition and maturation. Local blockade of retinoic acid production in the brain or excess dietary retinoic acid results in the failure of song maturation, yet does not affect prior song acquisition. Together these results yield significant insights into the role of vitamin A in maintaining neuronal plasticity and cognitive function in adulthood.

Figure 1

Timeline of critical periods within the zebra finch (T. guttata) song development and patterns of zRalDH expression in the song nuclei HVC, LMAN and RA (see text for proper names) of the zebra finch brain.

Figure 2

(A) Parasaggital view of direct and anterior pathways of the zebra finch (T. guttata) song system. Bold arrows show the direct motor pathway, while thin arrows delineate the anterior forebrain loop. Projections and nuclei that are known to express zRalDH are shown in gray, and nuclei with no expression are shown in white. (B) In situ hybridization of antisense riboprobe for the zRalDH shows strong expression in HVC and in the nidopallial layer of the telencephalon, including LMAN.