Circadian regulation of developmental synaptogenesis via the hypocretinergic system

The circadian clock orchestrates a wide variety of physiological and behavioral processes, enabling animals to adapt to daily environmental changes, particularly the day-night cycle. However, the circadian clock's role in the developmental processes remains unclear. Here, we employ the in vivo long-term time-lapse imaging of retinotectal synapses in the optic tectum of larval zebrafish and reveal that synaptogenesis, a fundamental developmental process for neural circuit formation, exhibits circadian rhythm. This rhythmicity arises primarily from the synapse formation rather than elimination and requires the hypocretinergic neural system. Disruption of this synaptogenic rhythm, by impairing either the circadian clock or the hypocretinergic system, affects the arrangement of the retinotectal synapses on axon arbors and the refinement of the postsynaptic tectal neuron's receptive field. Thus, our findings demonstrate that the developmental synaptogenesis is under hypocretin-dependent circadian regulation, suggesting an important role of the circadian clock in neural development.

Automated summary

By using in vivo long-term time-lapse imaging of retinotectal synapses in larval zebrafish, this study reveals that synaptogenesis exhibits circadian rhythm primarily through the formation rather than elimination of synapses, and it requires the hypocretinergic neural system's involvement. Disruption of this synaptogenic rhythm impacts the arrangement of retinotectal synapses and refinement of postsynaptic tectal neuron's receptive field. These findings demonstrate the hypocretin-dependent circadian regulation of developmental synaptogenesis, highlighting the important role of the circadian clock in neural development.