title: Frequency-dependent recruitment of fast amino acid and slow neuropeptide neurotransmitter release controls gonadotropin-releasing hormone neuron excitability.
abstract: The anteroventral periventricular nucleus (AVPV) is thought to play a key role in regulating the excitability of gonadotropin-releasing hormone (GnRH) neurons that control fertility. Using an angled, parahorizontal brain slice preparation we have undertaken a series of electrophysiological experiments to examine how the AVPV controls GnRH neurons in adult male and female mice. More than half (59%) of GnRH neurons located in the rostral preoptic area were found to receive monosynaptic inputs from the AVPV in a sex-dependent manner. AVPV stimulation frequencies <1 Hz generated short-latency action potentials in GnRH neurons with GABA and glutamate mediating >90% of the evoked fast synaptic currents. The AVPV GABA input was dominant and found to excite or inhibit GnRH neurons in a cell-dependent manner. Increasing the AVPV stimulation frequency to 5-10 Hz resulted in the appearance of additional poststimulus inhibitory as well as delayed excitatory responses in GnRH neurons that were independent of ionotropic amino acid receptors. The inhibition observed immediately following the end of the stimulation period was mediated partly by GABA(B) receptors, while the delayed activation was mediated by the neuropeptide kisspeptin. The latter response was essentially absent in Gpr54 knock-out mice and abolished by a Gpr54 antagonist. Together, these studies show that AVPV neurons provide direct amino acid and neuropeptidergic inputs to GnRH neurons. Low-frequency activation generates predominant GABA/glutamate release with higher frequency activation recruiting release of kisspeptin. This frequency-dependent release of amino acid and neuropeptide neurotransmitters greatly expands the range of AVPV control of GnRH neuron excitability.
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Xinhuai
authors.initials: X
authors.lastname: Liu
authors.forename: Robert
authors.initials: R
authors.lastname: Porteous
authors.forename: Xavier
authors.initials: X
authors.lastname: d'Anglemont de Tassigny
authors.forename: William H
authors.initials: WH
authors.lastname: Colledge
authors.forename: Robert
authors.initials: R
authors.lastname: Millar
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Petersen
authors.forename: Allan E
authors.initials: AE
authors.lastname: Herbison
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000166:cytology*; D001703:Biophysics; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011930:Reaction Time / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency; D000074502:Receptors, Kisspeptin-1; D018709:Statistics, Nonparametric; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C492248:Kiss1r protein, mouse; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D014633:Valine