title: The calcium oscillator of GnRH-1 neurons is developmentally regulated.
abstract: Oscillations in intracellular calcium levels have been described in GnRH-1 neurons in both prenatal and adult cells. However, differences have been reported in the mechanisms underlying these [Ca(2+)](i) oscillations, dependent on the model used. The goal of this study was to address whether these changes depend on the maturation status of GnRH-1 neurons by assaying prenatal GnRH-1 cells maintained in explants, at two different developmental stages. This report documents an increase in the frequency of [Ca(2+)](i) oscillations between 1 and 3 wk of in vitro maturation. During the early stage, [Ca(2+)](i) oscillations are blocked by tetrodotoxin and are mainly triggered by excitatory neurotransmitters, gamma-aminobutyric acid (GABA), and glutamate. In contrast, in the later stage, some cells exhibit residual tetrodotoxin-insensitive [Ca(2+)](i) oscillations, which are sustained by action potential-independent GABA and glutamate release. The strength of these two excitatory inputs remained relatively constant during the maturation process, and the increase in frequency of [Ca(2+)](i) oscillations observed at the later stage is due to a novel excitatory input carried by cholecystokinin. Together, these data indicate developmentally regulated release and interactions of neurotransmitters (known regulators of GnRH-1 cells in adults) and point to extrinsic factors regulating GnRH-1 cellular physiology.
authors.affiliation: Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke/National Institutes of Health, Bethesda, Maryland 20892-3703, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Constantin
authors.forename: Ulrike
authors.initials: U
authors.lastname: Klenke
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D048788:Growth and Development / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009830:Olfactory Bulb / Q000196:embryology / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D011498:Protein Precursors; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium