title: High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons.
abstract: Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1(ARH)) 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 Kiss1(ARH) neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1(ARH) neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1(ARH) 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 Kiss1(ARH) neurons. We propose that Kiss1(ARH) 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.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States.
authors.forename: Jian
authors.identifier: 0000-0002-4988-8587
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Nestor
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Padilla
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States.|Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Kelly
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States.|Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, United States.
authors.forename: Oline K
authors.initials: OK
authors.lastname: Rønnekleiv
mesh_terms: D000200:Action Potentials; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D055724:Electrophysiological Phenomena; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D059648:Kisspeptins / Q000378:metabolism*; D051379:Mice; D015287:Neurokinin B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D062308:Optogenetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D015287:Neurokinin B
keywords: GnRH; dynorphin; mouse; neurokinin B; neuropeptide; neuroscience; slow EPSP; synchronization