Hypothalamic Galanin-producing neurons regulate stress in zebrafish through a peptidergic, self-inhibitory loop

: Animals possess neuronal circuits inducing stress to avoid or cope with threats present in their surroundings, for instance, by promoting behaviors, such as avoidance and escape. However, mechanisms must exist to tightly control responses to stressors, since overactivation of stress circuits is deleterious for the wellbeing of an organism. The underlying neuronal dynamics responsible for controlling behavioral responses to stress have remained unclear. Here, we describe a neuronal circuit in the hypothalamus of zebrafish larvae that inhibits stress-related behaviors and prevents excessive activation of the neuroendocrine pathway hypothalamic-pituitary-interrenal axis. Central components of this circuit are neurons secreting the neuropeptide Galanin, as ablation of these neurons led to abnormally high levels of stress. Surprisingly, we found that Galanin has a self-inhibitory action on Galanin-producing neurons. Our results suggest that hypothalamic Galanin-producing neurons play an important role in fine-tuning stress responses by preventing potentially harmful overactivation of stress-regulating circuits.