Environmental enrichment has a variety of effects on the brains at many levels, ranging from molecular and cellular to behavioral; however, the precise mechanism underlying these effects remains uncertain. Kondo et al. from Hirokawa's lab found that enrichment causes BDNF-dependent KIF1A upregulation in mouse hippocampus. In neurons, KIF1A transports synaptic vesicle precursors containing synaptic proteins. Morphological and behavioral analysis of Kif1a^+/− and Bdnf^+/− mice revealed that a lack of KIF1A upregulation resulted in a loss of enrichment-induced hippocampal synaptogenesis and learning enhancement. In hippocampal neurons in vitro, BDNF enhanced KIF1A levels and KIF1A-mediated axonal transport. Furthermore, cell biological analysis revealed that KIF1A is essential for BDNF-induced synaptogenesis. Meanwhile, KIF1A over-expression promoted synaptogenesis via the formation of presynaptic boutons. These findings demonstrate that KIF1A is indispensable for BDNF-mediated hippocampal synaptogenesis and learning enhancement induced by enrichment. This is a new molecular motor-mediated presynaptic mechanism underlying experience-dependent neuroplasticity. Importantly, considering the beneficial effects of enrichment on brain disorders, KIF1A is a potentially important therapeutic target that merits further investigation.

Program member
Nobutaka Hirokawa (Department of Cell Biology and Anatomy, Graduate School of Medicine)

Figure 1 Standard housing cage (left) versus enriched cage (right).

Figure 2 BDNF-dependent KIF1A upregulation is required for enrichment-induced hippocampal synaptogenesis and learning enhancement.