Physical activity stimulates neurogenesis via sensory neuron activity in postembryonic zebrafish

Abstract

Physical exercise induces neurogenesis in adult and developing animal brains, but how exactly voluntary movement affects neurogenesis remains unclear. Here, we use two independent methods for immobilization, a physical barrier (gel matrix) or a genetic manipulation (CRISPR/Cas9 mutation of chrna1) to completely immobilize zebrafish larvae during postembryonic development. Both immobilization methods result in smaller brains, reduced brain cell proliferation, and accelerated neuronal differentiation. Conversely, exercised fish in a swim tunnel had larger brains, higher amounts of brain cell proliferation, and delayed neuronal differentiation. Interestingly, these effects of exercise could be mimicked by (1) increasing neural activity pharmacologically using GABAA receptor antagonist pentylenetetrazole systemically, or (2) by artificially activating the dorsal root ganglia (DRG) sensory neurons which also increases swimming, both of which increased cell proliferation and delayed neuronal differentiation. Finally, we dissociated the role of physical movement from that of neural activity by artificially activating the DRG neurons in CRISPR-chrna1 mutants, completely reversing the cell proliferative defects observed with immobilization.