Oxytocin regulates a diverse set of processes including stress, analgesia, metabolism, and social behavior. How such diverse functions are mediated by a single hormonal system is not well understood. Different functions of oxytocin could be mediated by distinct cell groups, yet it is currently unknown whether different oxytocinergic cell types exist that specifically mediate peripheral neuroendocrine or various central neuromodulatory processes via dedicated pathways. Using the Brainbow technique to map the morphology and projections of individual oxytocinergic cells in the larval zebrafish brain, we report here the existence of two main types of oxytocinergic cells; those that innervate the pituitary and those that innervate diverse brain regions. Similar to the situation in the adult rat and the adult midshipman, but in contrast to the situation in the adult trout, these two cell types are mutually exclusive and can be distinguished based on morphological and anatomical criteria. Further, our results reveal that complex oxytocinergic innervation patterns are already established in the larval zebrafish brain.
Significance Statement We used the Brainbow technique to reconstruct the morphology and projection patterns of oxytocinergic neurons in larval zebrafish, revealing diverse and complex brain-wide innervation patterns originating from a small cluster of cells within the neurosecretory preoptic area. Central target areas include the tectum, hypothalamus, and telencephalon. This is the first comprehensive whole-brain morphology characterization of oxytocinergic neurons to our knowledge. 3D registration reveals spatially distinct subtypes of oxytocinergic neurons. One group with morphologically complex projections reaches into distinct brain regions, presumably for neuromodulation, while another group features simpler projections innervating the pituitary, presumably for endocrine release. These two groups are spatially segregated, suggesting an evolutionarily ancient anatomical separation of oxytocin cell subtypes.
1 The authors declare no competing financial interests.
3 Max Planck Society; German Federal Office for Education and Research [01GQ1404]