Physical activity stimulates neurogenesis via sensory neuron activity in postembryonic zebrafish

Physical exercise induces neurogenesis in adult and developing animal brains, but how movement promotes 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, increased brain cell proliferation, and delayed neuronal differentiation. Interestingly, these effects of exercise could be mimicked by increasing neural activity pharmacologically using GABA A receptor antagonist pentylenetetrazol, or by artificially activating the dorsal root ganglia (DRG) sensory neurons, which increases swimming. Both promote cell proliferation and delayed neuronal differentiation. Finally, we dissociate the role of muscle contractions from neural activity by artificially activating the DRG neurons in CRISPR- chrna1 mutants, completely reversing neurogenesis defects that result from muscle paralysis.