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  • Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron.

Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron.

eLife (2021-01-20)
Xinhuai Liu, Shel-Hwa Yeo, H James McQuillan, Michel K Herde, Sabine Hessler, Isaiah Cheong, Robert Porteous, Allan E Herbison
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
SB 222200, ≥98% (HPLC), solid
Sigma-Aldrich
Neurokinin B, ≥95% (HPLC)
Sigma-Aldrich
CNQX, ≥98% (HPLC), solid
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
L-Glutamic acid, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid
Sigma-Aldrich
Anti-Rabbit-IgG - Atto 647N antibody produced in goat, 1 mg/mL IgG
Sigma-Aldrich
Anti-Green Fluorescent Protein Antibody, Chemicon®, from chicken