title: GABAergic transmission to kisspeptin neurons is differentially regulated by time of day and estradiol in female mice.
abstract: Gonadotropin-releasing hormone (GnRH) secretion is regulated by estradiol feedback. This feedback switches from negative to positive in females; this switch depends on time of day in many species. Estradiol feedback is likely conveyed via afferents. Kisspeptin neurons of the arcuate nucleus and anteroventral-periventricular region (AVPV) may differentially regulate GnRH neurons during negative and positive feedback, respectively. We tested estradiol and time of day regulation of GABAergic transmission and postsynaptic response to GABA in these two populations using transgenic mice with GFP-identified kisspeptin neurons. Ovariectomized (OVX) mice treated or not with estradiol (E) were studied in the AM (negative feedback) or PM (positive feedback). GABAA receptor reversal potential was unaffected by time of day or estradiol. GABA depolarized the membrane potential of arcuate neurons from OVX+E mice; this response was blunted in cells from OVX mice. GABA hyperpolarized AVPV kisspeptin neurons, except in the OVX PM group in which GABA did not alter membrane potential attributable to a PM hyperpolarization of baseline membrane potential. In both kisspeptin neuron populations from OVX mice, the frequency of GABAergic spontaneous postsynaptic currents was increased in the PM; this increase was blunted by estradiol. In arcuate, but not AVPV, kisspeptin neurons, estradiol reduced miniature postsynaptic current amplitude independent of time of day. Using nonstationary fluctuation analysis and diazepam to manipulate GABAA receptor apparent affinity, the decrease in arcuate miniature postsynaptic current amplitude was attributed to decreased number of receptors bound by GABA. Time of day and estradiol feedback thus both target presynaptic and postsynaptic mechanisms to differentially regulate kisspeptin neurons via GABAergic transmission.
authors.affiliation: Departments of Molecular and Integrative Physiology, defazio@umich.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: DeFazio
authors.affiliation: Departments of Molecular and Integrative Physiology, Obstetrics and Gynecology, and.
authors.forename: Carol F
authors.identifier: http://orcid.org/0000-0001-9878-9203
authors.initials: CF
authors.lastname: Elias
authors.affiliation: Departments of Molecular and Integrative Physiology, Obstetrics and Gynecology, and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Moenter
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000502:physiology*; D059648:Kisspeptins / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D059648:Kisspeptins; D011963:Receptors, GABA-A; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D003975:Diazepam
keywords: GnRH; diurnal; estradiol; feedback; kisspeptin; membrane potential