High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

J Qiu, CC Nestor, C Zhang, SL Padilla, RD Palmiter… - Elife, 2016 - elifesciences.org
J Qiu, CC Nestor, C Zhang, SL Padilla, RD Palmiter, MJ Kelly, OK Rønnekleiv
Elife, 2016elifesciences.org
Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal
development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus
(Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide
an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the
synaptic mechanisms of which are unknown. We characterized the cellular basis for
synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology …
Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function.
DOI: http://dx.doi.org/10.7554/eLife.16246.001
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