2025
Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell
Zapadka T, Tran N, Demb J. Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell. The Journal Of Physiology 2025 PMID: 39985791, DOI: 10.1113/jp286414.Peer-Reviewed Original ResearchOptic nerve crushRetinal ganglion cellsOptic nerveGanglion cellsSynaptic inputsVoltage-gated sodium channel currentsRetinal ganglion cell typesVoltage-gatedRetinal ganglion cell survivalChelation of intracellular calciumResting membrane potentialOptic nerve injuryVoltage-gated currentsAxonal injurySodium channel currentsRetinal ganglion cell axonsRGC typesAlpha retinal ganglion cellsAxon initial segmentIntracellular calciumRate of survivalNerve injuryElectrophysiological propertiesNerve crushIntrinsic excitability
2024
Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability
Mihailovich M, Germain P, Shyti R, Pozzi D, Noberini R, Liu Y, Aprile D, Tenderini E, Troglio F, Trattaro S, Fabris S, Ciptasari U, Rigoli M, Caporale N, D’Agostino G, Mirabella F, Vitriolo A, Capocefalo D, Skaros A, Franchini A, Ricciardi S, Biunno I, Neri A, Kasri N, Bonaldi T, Aebersold R, Matteoli M, Testa G. Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability. Journal Of Clinical Investigation 2024, 134: e168982. PMID: 39007270, PMCID: PMC11245157, DOI: 10.1172/jci168982.Peer-Reviewed Original ResearchConceptsCopy number variationsWilliams-Beuren syndromeRibosome biogenesisP-RPS6Neurodevelopmental disordersRibosomal genesP-4EBPNumber variationsTranslation factorsMicroduplication syndromeMolecular mechanismsGenesNeuronal differentiationPatient-derivedIntrinsic excitabilityMTOR pathwayBiogenesisNeuronal maturationPhosphorylated rpS6Neuronal transmissionWilliams-BeurenPathophysiological relevanceNeurocognitive featuresIntellectual disabilityDisease modelsFunctionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons
Rajebhosale P, Ananth M, Kim R, Crouse R, Jiang L, López-Hernández G, Zhong C, Arty C, Wang S, Jone A, Desai N, Li Y, Picciotto M, Role L, Talmage D. Functionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons. ELife 2024, 13: e86581. PMID: 38363713, PMCID: PMC10928508, DOI: 10.7554/elife.86581.Peer-Reviewed Original ResearchBasolateral amygdalaCholinergic neuronsThreatening stimuliMemory recallPredator odorDefensive behaviorResponse to predator odorBasal forebrain cholinergic projection neuronsBasal forebrain of micePosterior substantia innominataForebrain of miceSource of cholinergic inputCholinergic basal forebrainIncreased intrinsic excitabilityCholinergic projection neuronsThreat memoryFoot shockAversive stimuliChemogenetic silencingCholinergic inputSubstantia innominataPopulation of cholinergic neuronsNucleus basalisIntrinsic excitabilityProjection neurons
2023
Modulation of potassium conductances optimizes fidelity of auditory information
Kaczmarek L. Modulation of potassium conductances optimizes fidelity of auditory information. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216440120. PMID: 36930599, PMCID: PMC10041146, DOI: 10.1073/pnas.2216440120.Peer-Reviewed Original ResearchConceptsPotassium currentAuditory brainstem neuronsAuditory stimuliHigh-frequency firingGroups of neuronsLow-frequency stimuliBrainstem neuronsHigh-frequency stimuliIntrinsic excitabilityEnsembles of neuronsPostsynaptic neuronsAuditory neuronsNeurotransmitter releaseModulatory mechanismsAuditory stimulationFiring ratePotassium conductanceNeuronsPotassium channelsSingle neuronsAmplitude of currentsLoud soundsEnvironmental sound levelsChannel activityPositive membrane potentials
2021
The NaVy paradox: reducing sodium currents increases excitability
Kaczmarek LK. The NaVy paradox: reducing sodium currents increases excitability. Trends In Neurosciences 2021, 44: 767-768. PMID: 34373125, PMCID: PMC8813127, DOI: 10.1016/j.tins.2021.07.008.Peer-Reviewed Original ResearchConceptsSodium currentExcitatory neuronsIntrinsic excitabilityEpileptic seizuresPotassium channelsExcitabilityNeuronsSimilar effectsDisruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons
Runge K, Mathieu R, Bugeon S, Lafi S, Beurrier C, Sahu S, Schaller F, Loubat A, Herault L, Gaillard S, Pallesi-Pocachard E, Montheil A, Bosio A, Rosenfeld JA, Hudson E, Lindstrom K, Mercimek-Andrews S, Jeffries L, van Haeringen A, Vanakker O, Van Hecke A, Amrom D, Küry S, Ratner C, Jethva R, Gamble C, Jacq B, Fasano L, Santpere G, Lorente-Galdos B, Sestan N, Gelot A, Giacuzz S, Goebbels S, Represa A, Cardoso C, Cremer H, de Chevigny A. Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons. Molecular Psychiatry 2021, 26: 6125-6148. PMID: 34188164, PMCID: PMC8760061, DOI: 10.1038/s41380-021-01179-x.Peer-Reviewed Original ResearchConceptsLayer 5 neuronsKO miceForebrain glutamatergic neuronsTranscription factor NeuroD2Forebrain excitatory neuronsNeurodevelopmental disordersAutism spectrum disorderCortical projection neuronsPatch-clamp recordingsIntellectual disabilitySocial interaction deficitsSpontaneous seizuresCerebral cortexGlutamatergic neuronsSpine densityProjection neuronsIntrinsic excitabilityNervous system developmentNeuronal excitabilityExcitatory neuronsJuvenile miceBulk RNA sequencingSynaptic functionNeurobehavioral featuresDysregulated expressionSex-dependent role for EPHB2 in brain development and autism-associated behavior
Assali A, Cho JY, Tsvetkov E, Gupta AR, Cowan CW. Sex-dependent role for EPHB2 in brain development and autism-associated behavior. Neuropsychopharmacology 2021, 46: 2021-2029. PMID: 33649502, PMCID: PMC8429442, DOI: 10.1038/s41386-021-00986-8.Peer-Reviewed Original ResearchConceptsLayer V pyramidal neuronsAutism spectrum disorderSex-dependent roleAutism-associated behaviorsAttention deficit hyperactivity disorderPathophysiology of ASDSex-specific effectsNovo nonsense mutationFemale patientsPyramidal neuronsMotor hyperactivityIntrinsic excitabilityCortical functionRepetitive behaviorsSynaptic plasticityRelated disordersMemory deficitsBrain developmentHypofunctionReceptor tyrosine kinasesMiceHyperactivity disorderIntellectual disabilityDisordersEphB2
2020
Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline
George AA, Vieira JM, Xavier-Jackson C, Gee MT, Cirrito JR, Bimonte-Nelson HA, Picciotto MR, Lukas RJ, Whiteaker P. Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline. Journal Of Neuroscience 2020, 41: 555-575. PMID: 33239400, PMCID: PMC7821864, DOI: 10.1523/jneurosci.0876-20.2020.Peer-Reviewed Original ResearchMeSH Keywordsalpha7 Nicotinic Acetylcholine ReceptorAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBasal ForebrainCell LineCognitive DysfunctionElectrophysiological PhenomenaFemaleGenotypeHumansMaleMaze LearningMiceMice, TransgenicNeuronsParasympathetic Nervous SystemPeptide FragmentsSignal TransductionConceptsBasal forebrain cholinergic neuronsNeuronal intrinsic excitabilityAlzheimer's diseaseCholinergic neuronsDiagonal bandIntrinsic excitabilityAPP/PS1 transgenic miceCognitive declineCharacteristics of ADMedial septum-diagonal bandNicotinic acetylcholine receptor subtypesOligomeric amyloid betaAction potential firing rateForebrain cholinergic neuronsPS1 transgenic miceHorizontal diagonal bandLevels of amyloidSeptum-diagonal bandCurrent-clamp recordingsAcetylcholine receptor subtypesAction potential afterhyperpolarizationAge-matched littermatesOrganotypic slice culturesSpatial reference memoryHomomeric α7
2019
Potassium channel dysfunction in human neuronal models of Angelman syndrome
Sun A, Yuan Q, Fukuda M, Yu W, Yan H, Lim G, Nai M, D'Agostino G, Tran H, Itahana Y, Wang D, Lokman H, Itahana K, Lim S, Tang J, Chang Y, Zhang M, Cook S, Rackham O, Lim C, Tan E, Ng H, Lim K, Jiang Y, Je H. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science 2019, 366: 1486-1492. PMID: 31857479, PMCID: PMC7735558, DOI: 10.1126/science.aav5386.Peer-Reviewed Original ResearchConceptsAngelman syndromePotassium channel dysfunctionAS mouse modelUbiquitin protein ligase E3A (UBE3A) geneHuman neuronal modelNeuronal hyperexcitabilityNetwork hyperactivityAS patientsSeizure susceptibilitySynaptic dysfunctionModel miceIntrinsic excitabilityNeuronal excitabilityMouse modelBig potassium channelsHuman neuronsChannel dysfunctionEpilepsy susceptibilityBK channelopathyMouse neuronsPotassium channelsIndividual neuronsBrain organoidsNeuronsDysfunctionMonosodium Glutamate Triggers Neuroendocrine Stress Axis Leading to Apoptosis and Neural Progenitor Cell Activation
Mathew S, Joy K. Monosodium Glutamate Triggers Neuroendocrine Stress Axis Leading to Apoptosis and Neural Progenitor Cell Activation. The FASEB Journal 2019, 33: 554.1-554.1. DOI: 10.1096/fasebj.2019.33.1_supplement.554.1.Peer-Reviewed Original ResearchCRH gene expressionCRH neuronsHypothalamic-pituitary-adrenal (HPA) axisHPA axis sensitivityImmediate response to stressIncreased intrinsic excitabilityPlasma CORT concentrationsDay 8POMC mRNA expressionResponse to stressGlutamate inputsPlasma corticosteroneMonosodium glutamate exposureGlutamate modelMonosodium glutamateNeural stem/progenitor cell markersMale Wistar ratsBody weightMonosodium glutamate modelGroup I control ratsCORT concentrationsNegative feedback mechanismAxis sensitivityGroup II ratsIntrinsic excitability
2018
Celecoxib Ameliorates Seizure Susceptibility in Autosomal Dominant Lateral Temporal Epilepsy
Zhou L, Zhou L, Su L, Cao S, Xie Y, Wang N, Shao C, Wang Y, Zhou J, Cowell J, Shen Y. Celecoxib Ameliorates Seizure Susceptibility in Autosomal Dominant Lateral Temporal Epilepsy. Journal Of Neuroscience 2018, 38: 3346-3357. PMID: 29491011, PMCID: PMC5884462, DOI: 10.1523/jneurosci.3245-17.2018.Peer-Reviewed Original ResearchConceptsLeucine-rich glioma-inactivated 1Autosomal dominant lateral temporal epilepsyIntrinsic excitability of pyramidal neuronsExcitability of pyramidal neuronsGlioma-inactivated 1Seizure susceptibilityPyramidal neuronsIntrinsic excitabilityLateral temporal epilepsyGlutamatergic transmissionInherited syndromeTemporal epilepsyNonsynaptic epileptiform activityCytosolic phospholipase A<sub>2</sub>Nonsteroidal anti-inflammatory drugsCortical pyramidal neuronsAnti-inflammatory drugsKv1.2 expressionEpileptiform activityMutant miceFDA-approved drugsPathogenic basisCOX2 inhibitionCortical neuronsCelecoxib
2015
Intrinsic Neuronal Properties, Neural Networks, and Behavior
Levitan I, Kaczmarek L. Intrinsic Neuronal Properties, Neural Networks, and Behavior. 2015, 457-488. DOI: 10.1093/med/9780199773893.003.0018.ChaptersAction of neurotransmittersIntrinsic neuronal propertiesIntrinsic excitabilityStomatogastric ganglionCommand neuronsNeuronal propertiesDendritic treeAction potentialsNeuronsCellular mechanismsNetwork activitySensory informationIntrinsic electrical propertiesGangliaExcitabilityMost behaviorsNeurotransmittersHormone
2008
Mechanisms of response homeostasis during retinocollicular map formation
Shah RD, Crair MC. Mechanisms of response homeostasis during retinocollicular map formation. The Journal Of Physiology 2008, 586: 4363-4369. PMID: 18617562, PMCID: PMC2614012, DOI: 10.1113/jphysiol.2008.157222.Peer-Reviewed Original ResearchConceptsResponse homeostasisSynaptic plasticityIntrinsic excitabilityRetinocollicular map formationActivity-dependent developmentMouse superior colliculusHomeostatic plasticity mechanismsTotal synaptic inputReceptive fieldsDifferent mutant miceVisual receptive fieldsStrength of synapsesDifferent cellular mechanismsHebbian synaptic plasticityNeuronal outputSynaptic inputsSuperior colliculusRunaway excitationSynaptic scalingMutant miceNeural circuitsFunctional connectivityIndividual neuronsHomeostatic mechanismsCellular mechanismsProtein Kinase C Modulates Inactivation of Kv3.3 Channels*
Desai R, Kronengold J, Mei J, Forman SA, Kaczmarek LK. Protein Kinase C Modulates Inactivation of Kv3.3 Channels*. Journal Of Biological Chemistry 2008, 283: 22283-22294. PMID: 18539595, PMCID: PMC2494927, DOI: 10.1074/jbc.m801663200.Peer-Reviewed Original Research
2005
Regulation of the timing of MNTB neurons by short-term and long-term modulation of potassium channels
Kaczmarek LK, Bhattacharjee A, Desai R, Gan L, Song P, von Hehn CA, Whim MD, Yang B. Regulation of the timing of MNTB neurons by short-term and long-term modulation of potassium channels. Hearing Research 2005, 206: 133-145. PMID: 16081004, DOI: 10.1016/j.heares.2004.11.023.Peer-Reviewed Original ResearchConceptsAnteroventral cochlear nucleusPotassium channelsAuditory pathwayAction potentialsCentral auditory pathwayVoltage-dependent potassium channelsMammalian auditory pathwayAmount of neurotransmitterProtein phosphorylationMNTB neuronsGene expressionBushy cellsPrincipal neuronsTrapezoid bodyCochlear nucleusIntrinsic excitabilityMedial nucleusVoltage-dependent channelsFiring patternsNeuronsAmplitude of currentsKv1 familySound stimuliLong-term modulationSound localization
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