Neuron
Volume 109, Issue 2, 20 January 2021, Pages 331-346.e7
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Article
Reconstruction of the Hypothalamo-Neurohypophysial System and Functional Dissection of Magnocellular Oxytocin Neurons in the Brain

https://doi.org/10.1016/j.neuron.2020.10.032Get rights and content
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Highlights

  • A three-dimensional architecture of the HNS with high resolution was reconstructed

  • Magnocellular neuroendocrine cells collaterally projected to extrahypothalamic areas

  • Activation of Magno-OXT neurons promoted social behavior and peripheral OXT release

  • Inhibition of Magno-OXT neurons elicited opposite effects

Summary

The hypothalamo-neurohypophysial system (HNS), comprising hypothalamic magnocellular neuroendocrine cells (MNCs) and the neurohypophysis, plays a pivotal role in regulating reproduction and fluid homeostasis by releasing oxytocin and vasopressin into the bloodstream. However, its structure and contribution to the central actions of oxytocin and vasopressin remain incompletely understood. Using viral tracing and whole-brain imaging, we reconstruct the three-dimensional architecture of the HNS and observe collaterals of MNCs within the brain. By dual viral tracing, we further uncover that subsets of MNCs collaterally project to multiple extrahypothalamic regions. Selective activation of magnocellular oxytocin neurons promote peripheral oxytocin release and facilitate central oxytocin-mediated social interactions, whereas inhibition of these neurons elicit opposing effects. Our work reveals the previously unrecognized complexity of the HNS and provides structural and functional evidence for MNCs in coordinating both peripheral and central oxytocin-mediated actions, which will shed light on the mechanistic understanding of oxytocin-related psychiatric diseases.

Keywords

hypothalamo-neurohypophysial system
whole-brain imaging
reconstruction
magnocellular neuroendocrine cell
oxytocin
collaterals
social interaction

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