High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons
نویسندگان
چکیده
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.
منابع مشابه
Intermediary role of kisspeptin in the stimulation of gonadotropin-releasing hormone neurons by estrogen in the preoptic area of sheep brain
Introduction: The role of estrogen in the stimulation of gonadotropin-releasing hormone (GnRH) neurons is clear. These neurons do not express estrogen alpha receptors, so other mediator neurons should be present to transmit the positive feedback effect of estrogen to the GnRH neurons. Kisspeptin neurons have an important role in the stimulation of GnRH neurons, so they can be the mediator of...
متن کاملNeuroendocrine Role of Kisspeptin-Neurokinin B-Dynorphin Pathway in Male Fertility and its Correlation with Melatonin
Introduction: A subset of neurons has been recently identified in the arcuate nucleus of the hypothalamus that co-localize three neuropeptides; kisspeptin, neurokinin B, and dynorphin (KNDy). These neuropeptides have been shown to play a critical role in the central control of reproduction and the modulation of gonadotrophin releasing hormone (GnRH) secretion by endocrine, metabolic and environ...
متن کاملKisspeptin signaling is required for peripheral but not central stimulation of gonadotropin-releasing hormone neurons by NMDA.
NMDA and kisspeptins can stimulate gonadotropin-releasing hormone (GnRH) release after peripheral or central administration in mice. To determine whether these agonists act independently or through a common pathway, we have examined their ability to stimulate GnRH/luteinizing hormone (LH) release after peripheral or central administration in Kiss1- or Gpr54 (Kiss1r)-null mutant mice. Peripheral...
متن کاملSelective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion.
Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed c...
متن کاملKisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17β-Estradiol.
Kisspeptin is a neuropeptide that signals via a Gαq-coupled receptor, GPR54, in gonadotropin-releasing hormone (GnRH) neurons and is essential for pubertal maturation and fertility. Kisspeptin depolarizes and excites GnRH neurons primarily through the activation of canonical transient receptor potential (TRPC) channels and the inhibition of K+ channels. The gonadal steroid 17β-estradiol (E2) up...
متن کامل