TY - JOUR
T1 - High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons
AU - Qiu, Jian
AU - Nestor, Casey C.
AU - Zhang, Chunguang
AU - Padilla, Stephanie L.
AU - Palmiter, Richard D.
AU - Kelly, Martin J.
AU - Rønnekleiv, Oline K.
N1 - Publisher Copyright:
© Qiu et al.
PY - 2016/8/23
Y1 - 2016/8/23
N2 - Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) coexpress 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.
AB - Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) coexpress 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.
UR - http://www.scopus.com/inward/record.url?scp=84983646657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983646657&partnerID=8YFLogxK
U2 - 10.7554/eLife.16246
DO - 10.7554/eLife.16246
M3 - Article
C2 - 27549338
AN - SCOPUS:84983646657
SN - 2050-084X
VL - 5
JO - eLife
JF - eLife
IS - AUGUST
M1 - e16246
ER -