2020
GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions
Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, Taylor SR, Duman CH, Delpire E, Picciotto M, Wohleb ES, Duman RS. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. Journal Of Clinical Investigation 2020, 130: 1336-1349. PMID: 31743111, PMCID: PMC7269589, DOI: 10.1172/jci130808.Peer-Reviewed Original ResearchConceptsRapid antidepressant actionsAntidepressant actionGABA interneuronsMedial prefrontal cortexCell-specific knockdownPrinciple neuronsPrefrontal cortexDeletion of GluN2BSingle subanesthetic doseBehavioral actionsAction of ketamineNMDA receptor antagonistExcitatory postsynaptic currentsCellular triggersMajor unmet needKetamine's rapid antidepressant actionsGABA subtypeGluN2B-NMDARsSST interneuronsPostsynaptic currentsReceptor antagonistDepressed patientsSubanesthetic doseExtracellular glutamateMood disorders
2016
GABA interneurons mediate the rapid antidepressant-like effects of scopolamine
Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, Duman RS. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. Journal Of Clinical Investigation 2016, 126: 2482-2494. PMID: 27270172, PMCID: PMC4922686, DOI: 10.1172/jci85033.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexRapid antidepressant-like effectsRapid antidepressant effectsM1-AChRAntidepressant effectsGABA interneuronsSST interneuronsM1-type muscarinic acetylcholine receptorsNonselective muscarinic acetylcholine receptor antagonistMuscarinic acetylcholine receptor antagonistAcetylcholine receptor antagonistMuscarinic acetylcholine receptorsViral-mediated knockdownPromising pharmacological targetActivity-dependent synapticAntidepressant therapyGABAergic neuronsSomatostatin interneuronsGlutamatergic neuronsSocioeconomic burdenGABAergic interneuronsGlutamatergic interneuronsReceptor antagonist
2011
Regulation of NKB Pathways and Their Roles in the Control of Kiss1 Neurons in the Arcuate Nucleus of the Male Mouse
Navarro V, Gottsch M, Wu M, García-Galiano D, Hobbs S, Bosch M, Pinilla L, Clifton D, Dearth A, Ronnekleiv O, Braun R, Palmiter R, Tena-Sempere M, Alreja M, Steiner R. Regulation of NKB Pathways and Their Roles in the Control of Kiss1 Neurons in the Arcuate Nucleus of the Male Mouse. Endocrinology 2011, 152: 4265-4275. PMID: 21914775, PMCID: PMC3198996, DOI: 10.1210/en.2011-1143.Peer-Reviewed Original ResearchConceptsGnRH/LH secretionKNDy neuronsKiss1 neuronsGnRH neuronsLH secretionMale miceActions of NKBKiss1-expressing neuronsNegative feedback regulationAdult male miceReceptor-dependent pathwayDynorphin neuronsGonadotropin secretionArcuate nucleusPulsatile secretionDynorphin ANegative feedback effectNKB receptorNKBNeuronsSecretionFeedback regulationKiss1SenktidePutative role
2008
Excitatory Effects of the Puberty-Initiating Peptide Kisspeptin and Group I Metabotropic Glutamate Receptor Agonists Differentiate Two Distinct Subpopulations of Gonadotropin-Releasing Hormone Neurons
Dumalska I, Wu M, Morozova E, Liu R, van den Pol A, Alreja M. Excitatory Effects of the Puberty-Initiating Peptide Kisspeptin and Group I Metabotropic Glutamate Receptor Agonists Differentiate Two Distinct Subpopulations of Gonadotropin-Releasing Hormone Neurons. Journal Of Neuroscience 2008, 28: 8003-8013. PMID: 18685025, PMCID: PMC2597556, DOI: 10.1523/jneurosci.1225-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBarium CompoundsCapillariesChloridesDiagonal Band of BrocaDrug ResistanceElectrophysiologyFemaleGonadotropin-Releasing HormoneGreen Fluorescent ProteinsIn Vitro TechniquesMaleMedian EminenceMethoxyhydroxyphenylglycolMiceMice, TransgenicNeuronsPotassium ChannelsRatsRats, Sprague-DawleyReceptors, Metabotropic GlutamateRNA, MessengerSynapsesTumor Suppressor ProteinsVesicular Glutamate Transport Protein 2ConceptsMetabotropic glutamate receptor agonistGlutamate receptor agonistsGroup I metabotropic glutamate receptor agonistReceptor agonistGnRH neuronsGonadotropin-Releasing Hormone NeuronsG protein-coupled receptor GPR54Vesicular glutamate transporter 2GnRH-GFP miceRetrograde labeling techniqueGlutamate transporter 2Gonadotropin-releasing hormoneDistinct subpopulationsOnset of pubertyPostpubertal miceHormone neuronsGnRH cellsExcitatory effectsCentral releaseHypogonadotropic hypogonadismPeptide kisspeptinReceptor GPR54Brain slicesNormal pubertyKisspeptin
2007
Neurokinins robustly activate the majority of septohippocampal cholinergic neurons
Morozova E, Wu M, Dumalska I, Alreja M. Neurokinins robustly activate the majority of septohippocampal cholinergic neurons. European Journal Of Neuroscience 2007, 27: 114-122. PMID: 18184316, DOI: 10.1111/j.1460-9568.2007.05993.x.Peer-Reviewed Original ResearchConceptsSeptohippocampal cholinergic neuronsHippocampal acetylcholine releaseCholinergic neuronsNK3 receptorsHemokinin-1Acetylcholine releaseNK2 receptorsElectrophysiological effectsRat brain slice preparationWhole-cell patch-clamp recordingsMedial septum/diagonal bandDiagonal band neuronsNK3 receptor agonistPost-synaptic mechanismsStress-related affective disordersBrain slice preparationPatch-clamp recordingsEffect of NKCholinergic cellsNK receptorsReceptor agonistSlice preparationDiagonal bandNeurokinin receptorsBrain neurons
2006
Muscarine activates the sodium–calcium exchanger via M3 receptors in basal forebrain neurons
Xu C, Wu M, Morozova E, Alreja M. Muscarine activates the sodium–calcium exchanger via M3 receptors in basal forebrain neurons. European Journal Of Neuroscience 2006, 24: 2309-2313. PMID: 17074051, DOI: 10.1111/j.1460-9568.2006.05118.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasal GangliaBiotransformationDiagonal Band of BrocaDiphenylacetic AcidsElectrophysiologyIn Vitro TechniquesIon ChannelsIonsLithium ChlorideMaleMuscarineMuscarinic AgonistsPatch-Clamp TechniquesPiperidinesProsencephalonRatsRats, Sprague-DawleyReceptor, Muscarinic M3Sodium-Calcium ExchangerThioureaConceptsMuscarinic activationWhole-cell patch-clamp recording techniqueMedial septum/diagonal bandPatch-clamp recording techniquesSeptohippocampal GABAergic neuronsBasal forebrain neuronsMuscarinic cholinergic mechanismsRat brain slicesHippocampus-dependent learningHippocampal theta rhythmSodium-calcium exchangerIntraseptal carbacholMSDB neuronsCholinergic neuronsExcitatory actionGABAergic neuronsCholinergic mechanismsKB-R7943M3 receptorsForebrain neuronsDiagonal bandPrimary involvementBrain slicesHippocampal functionPotent modulator
2004
Histamine innervation and activation of septohippocampal GABAergic neurones: involvement of local ACh release
Xu C, Michelsen KA, Wu M, Morozova E, Panula P, Alreja M. Histamine innervation and activation of septohippocampal GABAergic neurones: involvement of local ACh release. The Journal Of Physiology 2004, 561: 657-670. PMID: 15486020, PMCID: PMC1665378, DOI: 10.1113/jphysiol.2004.071712.Peer-Reviewed Original ResearchConceptsLocal ACh releaseACh releaseGABAergic neuronesCholinergic neuronesSeptohippocampal cholinergicMedial septum/diagonal bandHistamine-induced activationGABAergic cell typesReceptor-selective antagonistHippocampal theta rhythmIndirect mechanismsConcentration-dependent mannerAtropine methylbromideHippocampal arousalGABAergic functionHistaminergic systemTuberomammillary nucleusCholinergic systemReceptor subtypesDiagonal bandHistamine effectSelective antagonistAlzheimer's diseaseGABAergic nucleusNeurodegenerative disordersHippocampal theta rhythm is reduced by suppression of the H‐current in septohippocampal GABAergic neurons
Xu C, Datta S, Wu M, Alreja M. Hippocampal theta rhythm is reduced by suppression of the H‐current in septohippocampal GABAergic neurons. European Journal Of Neuroscience 2004, 19: 2299-2309. PMID: 15090056, DOI: 10.1111/j.0953-816x.2004.03316.x.Peer-Reviewed Original ResearchConceptsHippocampal theta rhythmSeptohippocampal GABAergic neuronsGABAergic neuronsTheta rhythmH-currentMedial septum/diagonal bandRat brain slicesCholinergic neuronsGABAergic projectionsLocal infusionSpontaneous firingSelective blockadeDiagonal bandBrain slicesTheta burstsHippocampal learningNeuronsZD7288Underlying mechanismRhythmMemory taskGABAergicHippocampusBlockadeInfusion
2000
Muscarinic Tone Sustains Impulse Flow in the Septohippocampal GABA But Not Cholinergic Pathway: Implications for Learning and Memory
Alreja M, Wu M, Liu W, Atkins J, Leranth C, Shanabrough M. Muscarinic Tone Sustains Impulse Flow in the Septohippocampal GABA But Not Cholinergic Pathway: Implications for Learning and Memory. Journal Of Neuroscience 2000, 20: 8103-8110. PMID: 11050132, PMCID: PMC6772717, DOI: 10.1523/jneurosci.20-21-08103.2000.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAnimalsAtropineDiagonal Band of BrocaFluorescent DyesGamma-Aminobutyric AcidHippocampusIn Vitro TechniquesLearningMaleMemoryMuscarinic AgonistsMuscarinic AntagonistsNeural PathwaysNeuronsPatch-Clamp TechniquesRatsRats, Sprague-DawleyReceptor, Muscarinic M3Receptors, MuscarinicScopolamineSeptum of BrainSynaptic TransmissionConceptsHippocampal acetylcholine releaseSeptohippocampal cholinergic neuronsMuscarinic toneCholinergic neuronsCholinergic pathwaysAcetylcholine releaseImpulse flowNeurodegenerative disordersCognitive deficitsMedial septum/diagonal bandAmnesic effectMuscarinic cholinergic receptorsRat brain slicesSeptohippocampal cholinergic pathwaySeptohippocampal neuronsDisinhibitory mechanismGABA releaseGABAergic projectionsAxon collateralsCholinergic receptorsGABAergic pathwayMuscarinic receptorsSystemic infusionReceptor agonistSuccessful treatmentCholinergic Excitation of Septohippocampal GABA But Not Cholinergic Neurons: Implications for Learning and Memory
Wu M, Shanabrough M, Leranth C, Alreja M. Cholinergic Excitation of Septohippocampal GABA But Not Cholinergic Neurons: Implications for Learning and Memory. Journal Of Neuroscience 2000, 20: 3900-3908. PMID: 10804229, PMCID: PMC6772671, DOI: 10.1523/jneurosci.20-10-03900.2000.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAction PotentialsAnimalsAntibodies, MonoclonalCholinergic AgentsCognitionConditioning, PsychologicalElectrophysiologyGamma-Aminobutyric AcidHippocampusImmunotoxinsIn Vitro TechniquesMaleMemoryMuscarineMuscarinic AgonistsN-Glycosyl HydrolasesNeural InhibitionNeuronsRatsRats, Sprague-DawleyReceptor, Nerve Growth FactorReceptors, MuscarinicRibosome Inactivating Proteins, Type 1SaporinsSeptal NucleiSynaptic TransmissionTetrodotoxinTheta RhythmVasodilator AgentsConceptsMedial septum/diagonal bandSeptohippocampal cholinergic neuronsCholinergic neuronsCognition-enhancing effectsMuscarinic agonistsMuscarinic drugsContinuous theta rhythmHippocampal ACh releaseMuscarinic receptor antagonistMuscarinic cholinergic agonistRat brain slicesNovel fluorescent labelling techniqueDouble-labeling techniqueCholinergic excitationSeptohippocampal pathwayAcetylcholine releaseACh releaseDisinhibitory mechanismGABAergic pathwayReceptor antagonistUnlabeled neuronsCholinergic agonistsSystemic administrationDiagonal bandImpulse flow