Animals can respond differently to a sensory stimulus depending on its internal state (e.g. satiety/hunger). Neuromodulators are crucial in modulating the internal state of the animal. Gonadotropin-releasing hormone (GnRH) is a conserved neuropeptide and, modulates feeding and reproductive behaviors. It is produced by discrete neuronal populations located in the terminal nerve region of olfactory bulb (OB) and hypothalamus and is dispersed widely throughout the brain. Studies suggest that GnRH modulates the basal olfactory response by altering the synaptic properties of olfactory receptor neurons. However, the specific role of GnRH neuromodulation in olfactory information processing is not well understood.
To address this, first, we created a transgenic zebrafish line that labels the terminal nerve GnRH3 neurons with Gal4 transactivator and expressed a genetically encoded calcium indicator (GCaMP6s) in GnRH3 neurons. We imaged their activity by using two-photon microscopy and observed that GnRH3 neurons exhibit a high level of ongoing spontaneous activity. We showed that these neurons respond to a diverse set of olfactory stimuli and with strong preference for food related odors. Next, we found that genetic ablation of these neurons led to a significant decrease in feeding and food odor induced behavior. Moreover, this manipulation also led to decrease in food odour reponses in OB neurons. Finally, by optogenetic manipulation, we showed that these neurons modulate spontaneous activity of OB neurons suggesting a basal modulation of OB neural activity by GnRH3 neurons. Thus, our results suggest a central role for the GnRH neuromodulation in the regulation of OB activity, odor coding and olfactory behaviors.