Sleep is tightly regulated by the circadian clock and homeostatic mechanisms. The function of sleep is debated although it is established that the sleep/wake cycle is associated with structural and physiological synaptic changes that benefit the brain. Continuous imaging of single neuronal circuits in live animal is vital to understand the role of sleep in regulating synaptic dynamics. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate various functions including feeding, reward, sleep and wake. In the zebrafish model, few Hcrt neurons regulate sleep and wake, and its transparency enables time-lapse imaging of single synapses during both day and night. Here, we established the Gephyrin (Gphn) protein, a central inhibitory synapse organizer, as a fluorescent post-synaptic marker of inhibitory synapses. A transgenic zebrafish that expresses the fusion protein Gphn-EGFP in specific neurons of interest was generated. Double labeling showed that Gphn-tagRFP and Collybistin-EGFP clusters co-localized in dendritic inhibitory synapses. In the dendrites of Hcrt neurons, inhibitory synapse number is increased during development and is stabilized at 6 days post fertilization (dpf). To determine the effect of sleep on inhibitory synapse number, we performed two-photon live imaging of Gphn-EGFP clusters in Hcrt neurons during day and night, under light/dark and constant light and dark conditions, and following sleep deprivation. We found that synapse number is increased during the night and decreased during the day. These changes in synaptic number are eliminated under constant conditions and in sleep-deprived larvae. These results suggest that rhythmic structural plasticity of inhibitory synapses in Hcrt dendrites is independent of the circadian clock and is regulated by sleep pressure.