Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron
Xinhuai Liu,
Shel-Hwa Yeo,
H James McQuillan,
Michel K Herde,
Sabine Hessler,
Isaiah Cheong,
Robert Porteous,
Allan E Herbison
Affiliations
Xinhuai Liu
Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand
Shel-Hwa Yeo
Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
H James McQuillan
Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand
Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
The necessity and functional significance of neurotransmitter co-transmission remains unclear. The glutamatergic ‘KNDy’ neurons co-express kisspeptin, neurokinin B (NKB), and dynorphin and exhibit a highly stereotyped synchronized behavior that reads out to the gonadotropin-releasing hormone (GnRH) neuron dendrons to drive episodic hormone secretion. Using expansion microscopy, we show that KNDy neurons make abundant close, non-synaptic appositions with the GnRH neuron dendron. Electrophysiology and confocal GCaMP6 imaging demonstrated that, despite all three neuropeptides being released from KNDy terminals, only kisspeptin was able to activate the GnRH neuron dendron. Mice with a selective deletion of kisspeptin from KNDy neurons failed to exhibit pulsatile hormone secretion but maintained synchronized episodic KNDy neuron behavior that is thought to depend on recurrent NKB and dynorphin transmission. This indicates that KNDy neurons drive episodic hormone secretion through highly redundant neuropeptide co-transmission orchestrated by differential post-synaptic neuropeptide receptor expression at the GnRH neuron dendron and KNDy neuron.
