2019
Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior
Blanco-Centurion C, Luo S, Spergel DJ, Vidal-Ortiz A, Oprisan S, Van den Pol AN, Liu M, Shiromani PJ. Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior. Journal Of Neuroscience 2019, 39: 4986-4998. PMID: 31036764, PMCID: PMC6670248, DOI: 10.1523/jneurosci.0305-19.2019.Peer-Reviewed Original ResearchConceptsMelanin-concentrating hormoneRapid eye movement (REM) sleepMCH neuronsEye movement sleepREM sleepHypothalamic neuronsMovement sleepHypothalamic melanin-concentrating hormone (MCH) neuronsMelanin-concentrating hormone (MCH) neuronsNeuropeptide melanin-concentrating hormoneHypothalamic MCH neuronsIndividual hypothalamic neuronsMost brain neuronsFunctional activity mapsExploratory behaviorNon-REM sleepCalcium indicator GCaMP6Single neuron activityHormone neuronsNetwork activationBrain neuronsElectrophysiology studySame neuronsQuiet wakingIndicator GCaMP6s
2018
Neuropeptidergic modulation of GnRH neuronal activity and GnRH secretion controlling reproduction: insights from recent mouse studies
Spergel DJ. Neuropeptidergic modulation of GnRH neuronal activity and GnRH secretion controlling reproduction: insights from recent mouse studies. Cell And Tissue Research 2018, 375: 179-191. PMID: 30078104, DOI: 10.1007/s00441-018-2893-z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGnRH neuronsGnRH secretionGnRH neuronal activityGnRH neuronal firingRecent mouse studiesHormone secretionNeuronal activityNeuronal firingNeuropeptidergic modulationMouse studiesCognate receptorsNeuropeptidesNeuronsSecretionMammalian reproductionReproduction-related processesGonadotropinModulationMiceReceptors
2012
Effects of Leptin and Melanocortin Signaling Interactions on Pubertal Development and Reproduction
Israel DD, Sheffer-Babila S, de Luca C, Jo YH, Liu SM, Xia Q, Spergel DJ, Dun SL, Dun NJ, Chua SC. Effects of Leptin and Melanocortin Signaling Interactions on Pubertal Development and Reproduction. Endocrinology 2012, 153: 2408-2419. PMID: 22408174, PMCID: PMC3381095, DOI: 10.1210/en.2011-1822.Peer-Reviewed Original ResearchConceptsGnRH neuron activityNeuron activityGnRH neuronsFemale db/db miceDb/db miceMelanocortin 4 receptor activationNeuropeptides neuropeptide YAgouti-related peptideAction potential firingEffects of leptinC-fos expressionMelanocortin-4 receptorInitiation of pubertyHypothalamic hypogonadismDb miceNeuropeptide YMelanocortin agonistsLeptin receptorReceptor activationPubertal developmentΑ-MSHPubertal onsetMelanocortinLeptinDownstream mediatorKisspeptin Inhibits High-Voltage Activated Ca2+ Channels in GnRH Neurons via Multiple Ca2+ Influx and Release Pathways
Zhang XB, Spergel DJ. Kisspeptin Inhibits High-Voltage Activated Ca2+ Channels in GnRH Neurons via Multiple Ca2+ Influx and Release Pathways. Neuroendocrinology 2012, 96: 68-80. PMID: 22343183, DOI: 10.1159/000335985.Peer-Reviewed Original ResearchConceptsGnRH neuronsGnRH-green fluorescent protein transgenic miceG protein-coupled receptor 54Phospholipase C inhibitor edelfosineWhole-cell patch-clamp recordingsGonadotropin-releasing hormone (GnRH) secretionCanonical transient receptor potential (TRPC) channelsTransient receptor potential channelsRyR agonist caffeinePatch-clamp recordingsChelation of intracellularVGCC activityReceptor 54Kisspeptin-10Hormone secretionPeptide 234KP-10Antagonist caffeineBrain slicesSubsequent fertilityTransgenic miceTRPC channelsNeuronsDependent inhibitionCytoplasmic free
2009
Innervation of Gonadotropin-Releasing Hormone Neurons by Peptidergic Neurons Conveying Circadian or Energy Balance Information in the Mouse
Ward DR, Dear FM, Ward IA, Anderson SI, Spergel DJ, Smith PA, Ebling FJ. Innervation of Gonadotropin-Releasing Hormone Neurons by Peptidergic Neurons Conveying Circadian or Energy Balance Information in the Mouse. PLOS ONE 2009, 4: e5322. PMID: 19390688, PMCID: PMC2669176, DOI: 10.1371/journal.pone.0005322.Peer-Reviewed Original ResearchConceptsGnRH neuronsVasoactive intestinal peptidePeptidergic neuronsGonadotropin-Releasing Hormone NeuronsGnRH secretory systemVIP-IR fibersGonadotropin-releasing hormoneHypothalamic peptide systemsHormone neuronsBasal forebrainIntestinal peptideHypothalamic neuropeptidesPeptidergic fibersReproductive axisTransgenic miceModulatory inputsNeuronsCircadian timing informationPeptidergic signalsMetabolic statusMiceCircadian informationInnervationSignificant proportionPeptide system
2007
Calcium and Small-Conductance Calcium-Activated Potassium Channels in Gonadotropin-Releasing Hormone Neurons before, during, and after Puberty
Spergel DJ. Calcium and Small-Conductance Calcium-Activated Potassium Channels in Gonadotropin-Releasing Hormone Neurons before, during, and after Puberty. Endocrinology 2007, 148: 2383-2390. PMID: 17289846, PMCID: PMC3315592, DOI: 10.1210/en.2006-1693.Peer-Reviewed Original ResearchConceptsAdult GnRH neuronsSK channel expressionGnRH neuronsGnRH secretionSK currentPubertal increaseGnRH-green fluorescent protein transgenic miceChannel expressionSmall-conductance calcium-activated potassium channelsGonadotropin-releasing hormone (GnRH) neuronsSK channel blocker apaminCalcium-activated potassium channelsCytoplasmic freeChannel blocker apaminExcitatory synaptic inputsWhole-cell techniqueSK channel subtypesHormone neuronsBlocker apaminKisspeptin stimulationChannel blockersSK channelsBrain slicesChannel subtypesSynaptic inputs
2005
Impaired reproductive behavior by lack of GluR-B containing AMPA receptors but not of NMDA receptors in hypothalamic and septal neurons.
Shimshek DR, Bus T, Grinevich V, Single FN, Mack V, Sprengel R, Spergel DJ, Seeburg PH. Impaired reproductive behavior by lack of GluR-B containing AMPA receptors but not of NMDA receptors in hypothalamic and septal neurons. Endocrinology 2005, 20: 219-31. PMID: 16099814, DOI: 10.1210/me.2005-0262.Peer-Reviewed Original ResearchConceptsAMPA receptorsNMDA receptorsGnRH secretionMale miceN-methyl-D-aspartate receptorsLimbic system neuronsSerum testosterone levelsIsoxazolepropionic acid (AMPA) receptorsIonotropic glutamate receptorsNormal litter sizeMale sexual behaviorGnRH neuronsSeptal neuronsSystem neuronsOvarian morphologyGlutamate receptorsSeptal areaTestosterone levelsControl littermatesMale littermatesPup retrievalMajor subtypesTestis weightMaternal aggressionAcid receptors
2004
Neurotrophic effects of BDNF on embryonic gonadotropin‐releasing hormone (GnRH) neurons
Cronin AS, Horan TL, Spergel DJ, Brooks AN, Hastings MH, Ebling FJ. Neurotrophic effects of BDNF on embryonic gonadotropin‐releasing hormone (GnRH) neurons. European Journal Of Neuroscience 2004, 20: 338-344. PMID: 15233743, DOI: 10.1111/j.1460-9568.2004.03490.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain-Derived Neurotrophic FactorCell CountCells, CulturedCyclic AMP Response Element-Binding ProteinDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianGonadotropin-Releasing HormoneGreen Fluorescent ProteinsImmunoenzyme TechniquesImmunohistochemistryLuminescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMitogen-Activated Protein KinasesNeuritesNeuronsOligodeoxyribonucleotides, AntisensePotassium ChlorideReceptor, trkBConceptsBrain-derived neurotrophic factorGnRH cellsNeurotrophic factorMedian eminenceGonadotropin-releasing hormone (GnRH) neuronsNeurite outgrowthGnRH secretory systemGnRH-immunoreactive cellsGonadotropin-releasing hormoneDose-dependent increaseResponse element-binding proteinPhosphorylation of ERKHormone neuronsBDNF treatmentGnRH neuronsNeurotrophic effectsPreoptic areaNeurons migrateReproductive axisElement-binding proteinOlfactory placodeOlfactory tissuePrimary culturesERK pathwayGnRH
2003
A Confocal Microscopic Study of Gonadotropin-Releasing Hormone (GnRH) Neuron Inputs to Dopaminergic Neurons Containing Estrogen Receptor α in the Arcuate Nucleus of GnRH-Green Fluorescent Protein Transgenic Mice
Mitchell V, Loyens A, Spergel DJ, Flactif M, Poulain P, Tramu G, Beauvillain JC. A Confocal Microscopic Study of Gonadotropin-Releasing Hormone (GnRH) Neuron Inputs to Dopaminergic Neurons Containing Estrogen Receptor α in the Arcuate Nucleus of GnRH-Green Fluorescent Protein Transgenic Mice. Neuroendocrinology 2003, 77: 198-207. PMID: 12673053, DOI: 10.1159/000069511.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusBrain MappingDopamineEstrogen Receptor alphaFemaleGonadotropin-Releasing HormoneGreen Fluorescent ProteinsHypothalamusLuminescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMicroscopy, ConfocalNerve NetNeural PathwaysNeuronsReceptors, EstrogenTyrosine 3-MonooxygenaseConceptsGnRH-green fluorescent protein transgenic miceTH-ir neuronsTIDA neuronsArcuate nucleusGnRH neuronsDopaminergic neuronsFemale miceTransgenic miceTyrosine hydroxylase-immunoreactive neuronsTH monoclonal antibodyTuberoinfundibular dopaminergic neuronsHydroxylase-immunoreactive neuronsRole of estradiolAdult female miceDouble immunohistochemical stainingEstrogen receptor αGonadotropin-releasing hormone pathwayERalpha activationGnRH fibersImmunoreactive neuronsImmunohistochemical stainingBrain sectionsConfocal microscopic studiesReceptor αEstrus stage
2002
Codon‐improved Cre recombinase (iCre) expression in the mouse
Shimshek DR, Kim J, Hübner MR, Spergel DJ, Buchholz F, Casanova E, Stewart AF, Seeburg PH, Sprengel R. Codon‐improved Cre recombinase (iCre) expression in the mouse. Genesis 2002, 32: 19-26. PMID: 11835670, DOI: 10.1002/gene.10023.Peer-Reviewed Original ResearchConceptsDifferent mammalian cell linesMammalian codon usageHigh CpG contentCre activityMammalian cell linesEstrogen receptor hormoneCre fusion proteinGenetic experimentsDNA recombinationEpigenetic silencingCodon usageCoding sequenceCpG contentCre geneFunctional analysisFusion proteinCre recombinase expressionReceptor hormoneAdministration of tamoxifenRecombinase expressionCre recombinaseTemporal controlICreCre expressionCell lines
2001
Using reporter genes to label selected neuronal populations in transgenic mice for gene promoter, anatomical, and physiological studies
Spergel D, Krüth U, Shimshek D, Sprengel R, Seeburg P. Using reporter genes to label selected neuronal populations in transgenic mice for gene promoter, anatomical, and physiological studies. Progress In Neurobiology 2001, 63: 673-686. PMID: 11165000, DOI: 10.1016/s0301-0082(00)00038-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGreen fluorescent proteinReporter geneGene promoterSubcellular localization signalsCell type-specific expressionPromoter-driven reporter geneCorresponding reporter genesType-specific expressionLocalization signalReporter proteinNeuronal populationsPromoter elementsTransgenic miceFluorescent proteinTransgenic expressionGenesCell typesGonadotropin-releasing hormone (GnRH) neuronsGnRH neuronal networkPhysiological studiesPromoterProteinHormone neuronsBla genesExpression
1999
GABA- and Glutamate-Activated Channels in Green Fluorescent Protein-Tagged Gonadotropin-Releasing Hormone Neurons in Transgenic Mice
Spergel D, Krüth U, Hanley D, Sprengel R, Seeburg P. GABA- and Glutamate-Activated Channels in Green Fluorescent Protein-Tagged Gonadotropin-Releasing Hormone Neurons in Transgenic Mice. Journal Of Neuroscience 1999, 19: 2037-2050. PMID: 10066257, PMCID: PMC6782541, DOI: 10.1523/jneurosci.19-06-02037.1999.Peer-Reviewed Original ResearchConceptsGnRH neuronsPreoptic areaNucleated patchesWhole-cell recordingsApplication of GABANMDA receptor channelsGanglion terminaleHormone neuronsOrganum vasculosumSeptal nucleusDiagonal bandLamina terminalisNeuronal somataAxon terminalsOlfactory bulbMedian eminenceTransgenic miceFiring patternsNeuronsNeuronal dendritesReceptor channelsGABAGreen fluorescent proteinL-glutamateAMPA
1996
Immortalized GnRH Neurons Express Large-Conductance Calcium-Activated Potassium Channels
Spergel D, Catt K, Rojas E. Immortalized GnRH Neurons Express Large-Conductance Calcium-Activated Potassium Channels. Neuroendocrinology 1996, 63: 101-111. PMID: 9053774, DOI: 10.1159/000126946.Peer-Reviewed Original ResearchConceptsGT1-7 cellsGnRH secretory responseGnRH secretionChannel blockersBK channelsSecretory responseGonadotropin-releasing hormone (GnRH) neuronsEffects of charybdotoxinImmortalized GnRH neuronsPerforated-patch recordingsSmall conductance Ca2Patch-clamp recordingsBK channel blockersGamma-aminobutyric acidPatch-clamp techniqueLarge-conductance Ca2Cytoplasmic free Ca2Endoplasmic reticulum Ca2Hormone neuronsGnRH neuronsExcitatory neurotransmitterVoltage-dependent mannerSustained componentFura-2Whole-cell conductance
1994
Glutamate Modulates [Ca2+]i and Gonadotropin-Releasing Hormone Secretion in Immortalized Hypothalamic GT1-7 Neurons
Spergel D, Krsmanovic L, Stojilkovic S, Catt K. Glutamate Modulates [Ca2+]i and Gonadotropin-Releasing Hormone Secretion in Immortalized Hypothalamic GT1-7 Neurons. Neuroendocrinology 1994, 59: 309-317. PMID: 7911229, DOI: 10.1159/000126672.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCells, CulturedCycloleucineExcitatory Amino Acid AntagonistsFura-2GlutamatesGlutamic AcidGonadotropin-Releasing HormoneHypothalamusInositol PhosphatesMiceMice, TransgenicNeuronsNeurotoxinsReceptors, AMPAReceptors, GlutamateReceptors, N-Methyl-D-AspartateSpectrometry, FluorescenceConceptsDichlorokynurenic acidGnRH secretionMK-801Immortalized hypothalamic GT1-7 neuronsGonadotropin-Releasing Hormone SecretionOxo-4-isoxazolepropanoic acidAMPA/kainate antagonistGT1-7 cell lineAction of glutamateReceptor subtype agonistsNMDA receptor antagonistConcentration-dependent riseGT1-7 neuronsGT1-7 cellsKainate antagonistSubtype agonistsHormone secretionHypothalamic neuronsReceptor antagonistGlutamate actionSecretory responseNMDA receptorsGlycine siteCyclopentanedicarboxylic acidNeuroendocrine regulation