2025
Orexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity
Izawa S, Fusca D, Jiang H, Heilinger C, Hausen A, Wunderlich F, Steuernagel L, Kloppenburg P, Brüning J. Orexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity. Cell Reports 2025, 44: 115277. PMID: 39946231, DOI: 10.1016/j.celrep.2025.115277.Peer-Reviewed Original ResearchConceptsMelanin-concentrating hormoneNon-rapid eye movementFemale miceInhibitory responsesREM sleepMelanin-Concentrating Hormone NeuronsInsulin sensitivityReceptor type 2Melanin-concentrating hormone neuron populationImpaired insulin sensitivityNeuronal sub-populationsOX2R expressionOrexin neuronsOrexin signalingSelective agonistsModulate sleepBrain slicesClinical trialsOX2RRegulate sleepNarcolepsy treatmentOrexinNeuronal populationsRNA expressionType 2
2024
Astrocyte Ca2+ in the dorsal striatum suppresses neuronal activity to oppose cue-induced reinstatement of cocaine seeking
Tavakoli N, Malone S, Anderson T, Neeley R, Asadipooya A, Bardo M, Ortinski P. Astrocyte Ca2+ in the dorsal striatum suppresses neuronal activity to oppose cue-induced reinstatement of cocaine seeking. Frontiers In Cellular Neuroscience 2024, 18: 1347491. PMID: 39280793, PMCID: PMC11393831, DOI: 10.3389/fncel.2024.1347491.Peer-Reviewed Original ResearchCue-induced reinstatementCue-induced reinstatement of cocaine seekingCocaine self-administration experienceReinstatement of cocaine seekingCocaine Self-AdministrationSelf-administer cocaineSelf-administration experimentsCocaine seekingDorsal striatumSelf-AdministrationExtinction of cocaine-seeking behaviorCocaine self-administration groupResponse to acute cocaineCocaine-seeking behaviorDorsal striatum neuronsDrug-seeking behaviorNeuronal activitySelf-administration groupLong-term neuronal plasticityBrain slicesAcute cocaineReward processingCocaine groupNeuronal signalingAcute administrationElevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome
Xu J, Frankovich J, Liu R, Thienemann M, Silverman M, Farhadian B, Willett T, Manko C, Columbo L, Leibold C, Vaccarino F, Che A, Pittenger C. Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome. Brain Behavior And Immunity 2024, 122: 241-255. PMID: 39084540, PMCID: PMC11569416, DOI: 10.1016/j.bbi.2024.07.044.Peer-Reviewed Original ResearchPediatric Autoimmune Neuropsychiatric Disorders Associated with StreptococcusPediatric acute-onset neuropsychiatric syndromeStriatal cholinergic interneuronsCholinergic interneuronsObsessive-compulsive symptomsModulate basal ganglia functionNeuropsychiatric syndromeSignificant obsessive-compulsive symptomsBasal ganglia functionEx vivo brain slicesSevere food restrictionElevated antibodiesClinical historyPatient plasmaNeuropsychiatric manifestationsStreptococcus infectionBrain slicesSymptom flaresControl plasmaFood restrictionSerum antibodiesHuman brainInfectionAbrupt onsetClinical contextDevelopment of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain
Fernandes E, Palner M, Raval N, Jeppesen T, Danková D, Bærentzen S, Werner C, Eilts J, Maric H, Doose S, Aripaka S, Kaalund S, Aznar S, Kjaer A, Schlosser A, Haugaard-Kedström L, Knudsen G, Herth M, Stro̷mgaard K. Development of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain. Journal Of Medicinal Chemistry 2024, 67: 11975-11988. PMID: 38981131, DOI: 10.1021/acs.jmedchem.4c00615.Peer-Reviewed Original ResearchPostsynaptic densityBrain slicesPSD-95Tracer bindingPostsynaptic density protein 95Rat brain slicesMolecular imagingPost-mortem Parkinson's diseaseScaffold proteinQuantitative autoradiographyAbundant proteinsSynaptic transmissionPostsynaptic impairmentHigh-affinity inhibitorsSignaling moleculesImaging studiesFluorescent tagsCell imaging studiesDevelopment of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release
Zhou X, Stine C, Prada P, Fusca D, Assoumou K, Dernic J, Bhat M, Achanta A, Johnson J, Pasqualini A, Jadhav S, Bauder C, Steuernagel L, Ravotto L, Benke D, Weber B, Suko A, Palmiter R, Stoeber M, Kloppenburg P, Brüning J, Bruchas M, Patriarchi T. Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release. Nature Communications 2024, 15: 5353. PMID: 38918403, PMCID: PMC11199706, DOI: 10.1038/s41467-024-49712-0.Peer-Reviewed Original ResearchConceptsOpioid peptide releaseVentral tegmental areaAcute brain slicesN/OFQ actionsChemogenetic activationIn vivo studiesNociceptin/orphanin FQTegmental areaFibre photometryOpioid peptidesBrain slicesPharmacological profileGenetically encoded sensorIntracellular signal transducersReceptor ligandsPeptide releaseMammalian brainFunctional relevanceNeuronsBehavioral processesSignal transducerReleasePotential interactionsRegulatory functionsN/OFQMolecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo
Goodchild S, Shuart N, Williams A, Ye W, Parrish R, Soriano M, Thouta S, Mezeyova J, Waldbrook M, Dean R, Focken T, Ghovanloo M, Ruben P, Scott F, Cohen C, Empfield J, Johnson J. Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo. ACS Chemical Neuroscience 2024, 15: 1169-1184. PMID: 38359277, PMCID: PMC10958515, DOI: 10.1021/acschemneuro.3c00757.Peer-Reviewed Original ResearchExcitatory pyramidal neuronsPyramidal neuronsNeuronal action potential firingSeizure modelsActivity of excitatory neuronsInhibition of firingAction potential firingVoltage-gated sodium channelsSuppress epileptiform activityTherapeutic safety marginActivity ex vivoNeuronal hyperexcitabilityInhibitory interneuronsChannel inhibitorsEpileptiform activityInhibitory neuronsPotential firingExcitatory neuronsAntiseizure medicationsExcitatory circuitsBrain slicesReduced excitabilityPharmacological dissectionAntiseizure medication carbamazepineSodium channelsImpaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs
Zhu F, Shi Q, Jiang Y, Zhang Y, Zhao H. Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs. Molecular Autism 2024, 15: 9. PMID: 38297387, PMCID: PMC10829216, DOI: 10.1186/s13229-024-00587-4.Peer-Reviewed Original ResearchConceptsPrefrontal cortexPyramidal neuronsSHANK3 mutationsPrefrontal cortex neuronal activityPrefrontal cortex pyramidal neuronsSocial behaviorBrain slicesPrefrontal cortex's roleSynaptic transmissionPrefrontal cortex layersStudy social cognitionAutism spectrum disorderAutism-like behaviorsDendritic spine morphologyReduced dendritic complexitySocial cognitionSocial impairmentBehavioral alterationsNeural mechanismsExcitatory synaptic transmissionMutant rodent modelsHeightened anxietySpectrum disorderSpine densityImpaired synaptic function
2023
Electrical properties of dendritic spines
Zecevic D. Electrical properties of dendritic spines. Biophysical Journal 2023, 122: 4303-4315. PMID: 37837192, PMCID: PMC10698282, DOI: 10.1016/j.bpj.2023.10.008.Peer-Reviewed Original ResearchConceptsDendritic spinesIntracellular calcium concentration changesCortical pyramidal neuronsExcitatory synaptic transmissionCalcium concentration changesBasal dendritesPyramidal neuronsMushroom spinesSpine synapsesSynaptic transmissionBrain slicesVoltage-sensitive dyeNervous systemSpine neckSignificant physiological roleSynaptic signalingTwo-photon uncagingElectrical compartmentsSpineOnly experimental studiesBiochemical compartmentalizationPhysiological roleDifferent preparationsAnatomical structuresAdequate sensitivity
2022
Multiscale Computer Modeling of Spreading Depolarization in Brain Slices
Kelley C, Newton AJH, Hrabetova S, McDougal RA, Lytton WW. Multiscale Computer Modeling of Spreading Depolarization in Brain Slices. ENeuro 2022, 9: eneuro.0082-22.2022. PMID: 35927026, PMCID: PMC9410770, DOI: 10.1523/eneuro.0082-22.2022.Peer-Reviewed Original ResearchConceptsBrain slicesNeuronal spike rateGreater neuronal densityExtracellular spaceEffects of hypoxiaNeuronal densityNeurologic conditionsNeuronal depolarizationNeuronal silenceNeuronal volumeRelative hypoxiaSD velocityPathologic cycleECS volumeECS shrinkageSD speedMore dendritesSpike rateSDConcentration homeostasisNeuronsDepolarizationHypoxiaSlicesMultiscale computer modelingAMPK-mediated potentiation of GABAergic signalling drives hypoglycaemia-provoked spike-wave seizures
Salvati KA, Ritger ML, Davoudian PA, O'Dell F, Wyskiel DR, Souza GMPR, Lu AC, Perez-Reyes E, Drake JC, Yan Z, Beenhakker MP. AMPK-mediated potentiation of GABAergic signalling drives hypoglycaemia-provoked spike-wave seizures. Brain 2022, 145: 2332-2346. PMID: 35134125, PMCID: PMC9337815, DOI: 10.1093/brain/awac037.Peer-Reviewed Original ResearchConceptsSpike-wave seizuresAbsence epilepsyGABAB receptor functionThalamic brain slicesThalamocortical neuronsCircuit excitabilitySystemic administrationBrain slicesRodent modelsNeuronal activityDiabetes treatmentEpileptic seizuresSeizuresProtein kinaseProtein kinase activationAMPEpilepsyNetwork activityKinase activationMetabolismActivationProtein kinase agonistsEnergetic stressHypoglycaemiaKinase
2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2019
Using holographic illumination to study synaptic signal integration at individual dendritic spines
Weng J, Celis C, Zecevic D. Using holographic illumination to study synaptic signal integration at individual dendritic spines. 2019, 10865: 1086514. DOI: 10.1117/12.2507284.Peer-Reviewed Original ResearchSynaptic signal integrationExcitatory synaptic potentialsDendritic spinesSynaptic potentialsTemporal summationAcute cortical brain slicesIndividual synapsesLayer 5 pyramidal neuronsIndividual excitatory synapsesThin basal dendritesCortical brain slicesVoltage-sensitive dye recordingIndividual dendritic spinesSite of originSensory information processingBasal dendritesPyramidal neuronsExcitatory synapsesBrain slicesRepetitive activationVoltage-sensitive dyeSomatic recordingsSingle synapsesSynaptic signalsIndividual neurons
2018
Control of Spreading Depression with Electrical Fields
Whalen A, Xiao Y, Kadji H, Dahlem M, Gluckman B, Schiff S. Control of Spreading Depression with Electrical Fields. Scientific Reports 2018, 8: 8769. PMID: 29884896, PMCID: PMC5993812, DOI: 10.1038/s41598-018-26986-1.Peer-Reviewed Original ResearchConceptsElectric fieldField polarityDC electric fieldElectric field polarityElectrical controlOptical imagingPropagation pathIntrinsic optical imagingOpposite signDepression propagatesElectrical fieldField terminationElectro-chemical gradientPropagation velocityPropagatesFieldTraumatic brain injuryPropagationConfinementMore superficial layersDepression propagationBrain injurySynaptic transmissionBrain slicesWaves
2017
Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes
Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes. Cell Reports 2017, 20: 76-88. PMID: 28683325, PMCID: PMC5547898, DOI: 10.1016/j.celrep.2017.06.023.Peer-Reviewed Original ResearchConceptsAD transgenic mouse modelDisease pathologyMetabotropic glutamate receptor 5Allosteric modulationGlutamate receptor 5Alzheimer's disease pathologyTransgenic mouse brainSilent allosteric modulatorsTransgenic mouse modelBroad therapeutic windowMouse phenotypeAD interventionSynaptic depletionBrain slicesGlutamate signalingMouse modelTherapeutic windowAD phenotypeReceptor 5Mouse brainAllosteric modulatorsMemory deficitsCellular prion proteinPathological roleMGluR5The stochastic nature of action potential backpropagation in apical tuft dendrites
Short SM, Oikonomou KD, Zhou WL, Acker CD, Popovic MA, Zecevic D, Antic SD. The stochastic nature of action potential backpropagation in apical tuft dendrites. Journal Of Neurophysiology 2017, 118: 1394-1414. PMID: 28566465, PMCID: PMC5558024, DOI: 10.1152/jn.00800.2016.Peer-Reviewed Original ResearchConceptsDendritic CaPyramidal neuronsApical tuftCortical pyramidal neuronsAction potential backpropagationRat brain slicesSpontaneous synaptic inputsDifferent cortical layersVoltage-gated CaAP backpropagationAP burstsGlutamate iontophoresisSynaptic contactsSomatic APsApical trunkAP frequencyBrain slicesDendritic physiologySynaptic inputsCortical layersChannel inactivationLocal NaNeuronsSpike-timing dependent plasticityTrials
2016
Activation of α7 nicotinic acetylcholine receptors facilitates long-term potentiation at the hippocampal-prefrontal cortex synapses in vivo
Stoiljkovic M, Kelley C, Nagy D, Hurst R, Hajós M. Activation of α7 nicotinic acetylcholine receptors facilitates long-term potentiation at the hippocampal-prefrontal cortex synapses in vivo. European Neuropsychopharmacology 2016, 26: 2018-2023. PMID: 27866776, DOI: 10.1016/j.euroneuro.2016.11.003.Peer-Reviewed Original ResearchConceptsHippocampal-medial prefrontal cortex pathwayHippocampal-prefrontal cortex pathwayLong-term potentiationPrefrontal cortex pathwayCognitive processesCortex pathwayCognitive effectsMnemonic functionsCognitive functionMemory formationNeurophysiological effectsΑ7-nAChR activationNAChR activationΑ7 nAChRsHippocampal long-term potentiationSubiculum regionsΑ7 nicotinic acetylcholine receptorNicotinic acetylcholine receptorsMale ratsSaline controlsSynaptic transmissionBrain slicesTetanic stimulationAcetylcholine receptorsSynaptic plasticityZika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, Dell’Anno M, Gulden FO, Pochareddy S, Tebbenkamp AT, Han W, Pletikos M, Gao T, Zhu Y, Bichsel C, Varela L, Szigeti-Buck K, Lisgo S, Zhang Y, Testen A, Gao XB, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Reports 2016, 16: 2576-2592. PMID: 27568284, PMCID: PMC5135012, DOI: 10.1016/j.celrep.2016.08.038.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseBrainCell DeathCentrosomeFetusGene Expression ProfilingHumansImmunity, InnateMicrocephalyMitochondriaMitosisNeocortexNeural Stem CellsNeuroepithelial CellsNeurogliaNeuronsNeuroprotective AgentsNucleosidesPhosphorylationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSpinal CordTranscription, GeneticVirus ReplicationZika VirusZika Virus InfectionConceptsRadial glial cellsNES cellsNeuroepithelial stem cellsZIKV infectionFetal brain slicesStem cellsEarly human neurodevelopmentHuman neuroepithelial stem cellsHuman neural stem cellsCell deathSingle-cell RNA-seqNeural stem cellsNeurodevelopment defectsZIKV replicationGlial cellsBrain slicesPotential treatmentRadial gliaZika virusPhospho-TBK1Neurodevelopmental defectsRNA-seqSupernumerary centrosomesNucleoside analoguesHuman neurodevelopmentOligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease*
Haas LT, Strittmatter SM. Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease*. Journal Of Biological Chemistry 2016, 291: 17112-17121. PMID: 27325698, PMCID: PMC5016115, DOI: 10.1074/jbc.m116.720664.Peer-Reviewed Original ResearchConceptsProtein tyrosine kinase 2Calmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IICellular prion proteinProtein kinase IIBrain slicesSignaling cascadesAlzheimer's diseaseKinase IIPhysiological signalingKinase 2Mutant transgeneMetabotropic glutamate receptor 5Loss of synapsesPrion proteinGlutamate receptor 5Receptor complexWild-type slicesProtein mediatorsAmyloid-β OligomersGlutamate activationChronic expressionDementia symptomsReceptor 5Acute exposureDistinct Functional Groups Emerge from the Intrinsic Properties of Molecularly Identified Entorhinal Interneurons and Principal Cells.
Ferrante M, Tahvildari B, Duque A, Hadzipasic M, Salkoff D, Zagha EW, Hasselmo ME, McCormick DA. Distinct Functional Groups Emerge from the Intrinsic Properties of Molecularly Identified Entorhinal Interneurons and Principal Cells. Cerebral Cortex 2016, 27: 3186-3207. PMID: 27269961, PMCID: PMC6059165, DOI: 10.1093/cercor/bhw143.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiophysicsCell CountCluster AnalysisDNA-Binding ProteinsElectric StimulationEntorhinal CortexGreen Fluorescent ProteinsIn Vitro TechniquesInterneuronsIntracellular Signaling Peptides and ProteinsMembrane PotentialsMiceMice, TransgenicNeuropeptide YParvalbuminsPatch-Clamp TechniquesProteinsReceptors, Serotonin, 5-HT3Transcription FactorsVasoactive Intestinal PeptideProtective Effects of Chlorogenic Acid and its Metabolites on Hydrogen Peroxide-Induced Alterations in Rat Brain Slices: A Comparative Study with Resveratrol
Gul Z, Demircan C, Bagdas D, Buyukuysal R. Protective Effects of Chlorogenic Acid and its Metabolites on Hydrogen Peroxide-Induced Alterations in Rat Brain Slices: A Comparative Study with Resveratrol. Neurochemical Research 2016, 41: 2075-2085. PMID: 27161374, DOI: 10.1007/s11064-016-1919-8.Peer-Reviewed Original ResearchConceptsOxidative stress parametersCortical slicesRat brain slicesRat cortical slicesStress parametersChlorogenic acidChloride stainingProtective effectBrain slicesOxidative stressQuinic acidResveratrolNatural phenolic compoundsMain metaboliteMalondialdehydeCaffeic acidROS levelsIncubation mediumPhenolic compoundsAlterationsIC50 valuesPresent studyStainingΜM H2O2Oxygen species
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