Highly redundant neuropeptide volume cotransmission underlying episodic activation of the GnRH neuron dendron
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 but non-synaptic appositions with the GnRH neuron dendron. Confocal GCaMP6 calcium imaging demonstrated that, of the neurotransmitters co-expressed by KNDy neurons, only kisspeptin was able to activate the GnRH neuron dendron. The selective deletion of kisspeptin from KNDy neurons resulted in mice in which the synchronized behavior of the KNDy neurons was maintained but their ability to drive episodic hormone secretion was abolished. This indicates that KNDy neurons drive episodic hormone secretion through converse modes of highly redundant neuropeptide co-transmission orchestrated by differential postsynaptic neuropeptide receptor expression at their two target sites.