Optogenetic activation of hypothalamic AgRP neurons in transgenic zebrafish larvae increased food intake.

Agouti Related Peptide (AgRP) neurons are located in the hypothalamus, and upon stimulation, these neurons regulate hunger and hunger-mediated behaviors, especially food-seeking and compulsive eating. AgRP neurons are naturally activated by ghrelin binding onto the ghrelin receptors on the neuron surface during starvation or fasting state to evoke the aforementioned behaviors. In this study, we used channelrhodopsin (ChR2), an optogenetic actuator, to control AgRP neuronal activity. For the first time, we observed food-intake behavior in zebrafish larvae by optogenetically triggering AgRP1 neurons. We created a transgenic line, Tg(AgRP1:ChR2-Kaede), where ChR2-Kaede is expressed in AgRP1 neurons. Transgenic zebrafish Tg(AgRP1:ChR2-Kaede) larvae at 6 days post fertilization and wild-type (ABWT) larvae were used to compare the suction behavior. We found that AgRP1 neuron activation in transgenic larvae led to a significantly higher food-consumption behavior than wildtype larvae when analyzed using Particle Image Velocimetry (PIV) to calculate the food particle velocity initiated by larval suction behavior. These findings in this novel transgenic zebrafish model would be useful in studying various hunger-related behaviors, their underlying neural circuits, and substrates subjected to different chemical stimuli, including drugs of abuse.