Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
Casey C Nestor
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
Chunguang Zhang
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
Stephanie L Padilla
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States
Richard D Palmiter
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States
Martin J Kelly
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
Oline K Rønnekleiv
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
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.
