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
Ectopic reconstitution of a spine-apparatus-like structure provides insight into mechanisms underlying its formation
Falahati H, Wu Y, Fang M, De Camilli P. Ectopic reconstitution of a spine-apparatus-like structure provides insight into mechanisms underlying its formation. Current Biology 2024, 35: 265-276.e4. PMID: 39626668, PMCID: PMC11753949, DOI: 10.1016/j.cub.2024.11.010.Peer-Reviewed Original ResearchEndoplasmic reticulumSpine apparatusActin bundlesEndomembrane networkER sheetsConserved regionProtein synaptopodinCisternal organelleNon-neuronal cellsER cisternsOrganellesSynaptopodinProteinNeuronal dendritesNeuronal spinesAxon initial segmentFindings shed lightBiogenesisActinProtein matrixNarrow lumenReticulumMammalsInitial segmentMechanismHuman IPSC-Derived Microglia Sense and Dampen Hyperexcitability of Cortical Neurons Carrying the Epilepsy-Associated SCN2A-L1342P Mutation
Que Z, Olivero-Acosta M, Robinson M, Chen I, Zhang J, Wettschurack K, Wu J, Xiao T, Otterbacher C, Shankar V, Harlow H, Hong S, Zirkle B, Wang M, Cui N, Mandal P, Chen X, Deming B, Halurkar M, Zhao Y, Rochet J, Xu R, Brewster A, Wu L, Yuan C, Skarnes W, Yang Y. Human IPSC-Derived Microglia Sense and Dampen Hyperexcitability of Cortical Neurons Carrying the Epilepsy-Associated SCN2A-L1342P Mutation. Journal Of Neuroscience 2024, 45: e2027232024. PMID: 39557580, PMCID: PMC11735681, DOI: 10.1523/jneurosci.2027-23.2024.Peer-Reviewed Original ResearchNeuronal excitabilityHyperexcitable neuronsHuman microgliaCo-cultureVoltage-gated sodium channel Nav1.2Neuronal activityRepetitive action potential firingRodent models of seizuresBrain-resident immune cellsSodium channel expressionInfluence neuronal excitabilityAction potential firingHyperexcitability of cortical neuronsModulates neuronal excitabilityEpilepsy-causing mutationsSodium channel Nav1.2Resident immune cellsAbnormal neuronal activityPresence of microgliaSuppression of seizuresModulate neuronal activityDensity of sodium channelsModels of seizuresPresence of neuronsAxon initial segmentDisease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons
Wu J, Quraishi I, Zhang Y, Bromwich M, Kaczmarek L. Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons. Cell Reports 2024, 43: 113904. PMID: 38457342, PMCID: PMC11013952, DOI: 10.1016/j.celrep.2024.113904.Peer-Reviewed Original ResearchInhibitory neuronsRegulation of neuronal excitabilityPotassium channel mutationsVoltage-dependent sodiumInhibitory cortical neuronsGain-of-function mutationsAxon initial segmentKCNT1 geneNeuronal excitabilityChannel subunitsChannel mutationsNetwork hyperexcitabilityMouse modelNeuron typesCortical neuronsTreat epilepsyNeuronsExcitable neuronsNeurological disordersSevere intellectual disabilityMutationsInitial segmentKCNT1ExpressionHyperexcitability
2022
Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines
Falahati H, Wu Y, Feuerer V, Simon HG, De Camilli P. Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203750119. PMID: 36215465, PMCID: PMC9586327, DOI: 10.1073/pnas.2203750119.Peer-Reviewed Original ResearchConceptsSpine apparatusDendritic spinesSubset of neuronsAxon initial segmentDendritic shaftsER cisternsNonneuronal cellsSynaptopodinSpineSmooth endoplasmic reticulumEndoplasmic reticulumCisternal organelleInitial segmentSpecific localizationCisternsBinding proteinPDLIM7Expression patternsSubsetProteinSmall subsetDiseaseNeuronsBrainFunctional partnership
2020
Whole-Cell Photobleaching Reveals Time-Dependent Compartmentalization of Soluble Proteins by the Axon Initial Segment
Nicholson L, Gervasi N, Falières T, Leroy A, Miremont D, Zala D, Hanus C. Whole-Cell Photobleaching Reveals Time-Dependent Compartmentalization of Soluble Proteins by the Axon Initial Segment. Frontiers In Cellular Neuroscience 2020, 14: 180. PMID: 32754013, PMCID: PMC7366827, DOI: 10.3389/fncel.2020.00180.Peer-Reviewed Original ResearchSoluble proteinAxon initial segmentCytoplasmic soluble proteinsForm of compartmentalizationIntact F-actinSuper-resolution fluorescence imagingSpectrin cytoskeletonSpecific proteinsF-actinProtein accumulationAxonal compartmentProtein exchangeProteinCompartmentalizationSomatodendritic compartmentNeuronal morphologyInitial segmentImportant insightsUltrastructureCompartmentsFluorescence imagingPhotobleachingCytoskeletonSignalingDifferentiation
2019
Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly
Yang R, Walder-Christensen KK, Lalani S, Yan H, García-Prieto ID, Álvarez S, Fernández-Jaén A, Speltz L, Jiang YH, Bennett V. Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 19717-19726. PMID: 31451636, PMCID: PMC6765234, DOI: 10.1073/pnas.1909989116.Peer-Reviewed Original ResearchConceptsΒ4-spectrinAxon initial segmentC-terminal domainNormal neural developmentPrevents recruitmentGiant ankyrinNeural developmentConformational changesMissense mutationsMutationsPhosphorylationSegment assemblyRecruitmentMouse brainClose appositionCore mechanismDomainAssemblyAnkyrinClosed configurationIntermediate stageInitial segmentSitesProximal axonsDistinct molecular programs regulate synapse specificity in cortical inhibitory circuits
Favuzzi E, Deogracias R, Marques-Smith A, Maeso P, Jezequel J, Exposito-Alonso D, Balia M, Kroon T, Hinojosa A, F Maraver E, Rico B. Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits. Science 2019, 363: 413-417. PMID: 30679375, DOI: 10.1126/science.aau8977.Peer-Reviewed Original ResearchConceptsCortical inhibitory circuitsInhibitory circuitsClasses of GABAergic interneuronsInvestigate transcriptional dynamicsClasses of interneuronsConnectivity patternsAxon initial segmentGABAergic interneuronsMammalian cerebral cortexTranscriptional dynamicsCortical interneuronsPyramidal cellsSynapse specificityPostnatal developmentInterneuron diversityInterneuronsCerebral cortexMolecular mechanismsConnectivity motifsSynaptic moleculesBrain functionMolecular programsNeuronal connectivityInformation processingFunctional networks
2016
FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon
Dover K, Marra C, Solinas S, Popovic M, Subramaniyam S, Zecevic D, D’Angelo E, Goldfarb M. FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon. Nature Communications 2016, 7: 12895. PMID: 27666389, PMCID: PMC5052690, DOI: 10.1038/ncomms12895.Peer-Reviewed Original ResearchCentral nervous systemAction potentialsNervous systemSodium action potentialsGranule cell axonsAxon initial segmentCerebellar granule cellsNodes of RanvierCell axonsSomatodendritic membraneVertebrate central nervous systemGranule cellsCerebellar granule cell axonsDistal axonsSpike conductionAxonsSodium channels
2015
Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells
Breslow DK, Nachury MV. Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells. Methods In Cell Biology 2015, 127: 203-221. PMID: 25837393, PMCID: PMC4797650, DOI: 10.1016/bs.mcb.2014.12.006.BooksConceptsSemipermeabilized cellsProtein entriesPrimary ciliaCiliary diffusion barrierNuclear pore complexPrimary cilia functionPore complexMammalian cellsSignal transductionSpecialized compartmentsCilia functionPlasma membraneCiliary membraneIntact cellsExperimental perturbationsCell surfaceProtein exchangeCiliaVitro systemAxon initial segmentMechanistic analysisChapter 11 AnalysisUnique resourceCapture assayCells
2014
Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy
Oliva MK, McGarr TC, Beyer BJ, Gazina E, Kaplan DI, Cordeiro L, Thomas E, Dib-Hajj SD, Waxman SG, Frankel WN, Petrou S. Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy. Neurobiology Of Disease 2014, 67: 180-190. PMID: 24657915, PMCID: PMC4298829, DOI: 10.1016/j.nbd.2014.03.007.Peer-Reviewed Original ResearchConceptsAxon initial segmentAbsence epilepsyMouse modelGenetic absence epilepsyNav channelsSCN2A variantsInitial segment
2013
An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier
Breslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV. An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. Journal Of Cell Biology 2013, 203: 129-147. PMID: 24100294, PMCID: PMC3798247, DOI: 10.1083/jcb.201212024.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsCell LineCell MembraneCell Membrane PermeabilityCiliaDiffusionMiceMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMolecular WeightNuclear PoreProtein TransportProteinsRecombinant Fusion ProteinsReproducibility of ResultsTime FactorsTime-Lapse ImagingTransfectionConceptsNuclear pore complexCiliary diffusion barrierPore complexActin cytoskeletonMembrane proteinsActive transportPrimary ciliaPlasma membraneCiliary membraneSpecific proteinsLarge proteinsMechanistic basisPermeabilized cellsProteinCiliaAxon initial segmentMembraneCellsCytoskeletonInitial segmentEntryTransportAssaysVivoComplexes
2012
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier
Gasser A, Ho TS, Cheng X, Chang KJ, Waxman SG, Rasband MN, Dib-Hajj SD. An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier. Journal Of Neuroscience 2012, 32: 7232-7243. PMID: 22623668, PMCID: PMC3413458, DOI: 10.1523/jneurosci.5434-11.2012.Peer-Reviewed Original ResearchConceptsReporter proteinAxon initial segmentKinase phosphorylation siteSodium channelsIntracellular loop 2Nodes of RanvierFull-length channelGlutamic acid residuesPhosphorylation sitesMechanism of channelVoltage-gated sodium channelsAcid residuesLoop 2Functional mouseNav1.6 sodium channelsMotifProteinVivo analysisAnkyrinGSomatodendritic compartmentCultured neuronsInitial segmentVivoAction potentialsCellsA Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly
Galiano MR, Jha S, Ho TS, Zhang C, Ogawa Y, Chang KJ, Stankewich MC, Mohler PJ, Rasband MN. A Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly. Cell 2012, 149: 1125-1139. PMID: 22632975, PMCID: PMC3361702, DOI: 10.1016/j.cell.2012.03.039.Peer-Reviewed Original Research
2011
Active Action Potential Propagation But Not Initiation in Thalamic Interneuron Dendrites
Casale A, McCormick D. Active Action Potential Propagation But Not Initiation in Thalamic Interneuron Dendrites. Journal Of Neuroscience 2011, 31: 18289-18302. PMID: 22171033, PMCID: PMC3269759, DOI: 10.1523/jneurosci.4417-11.2011.Peer-Reviewed Original ResearchConceptsDorsal lateral geniculate nucleusLateral geniculate nucleusSomatic current injectionAction potentialsDendritic arborsGeniculate nucleusSynaptic stimulationThalamic interneuronsMouse dorsal lateral geniculate nucleusDendritic neurotransmitter releaseEntire dendritic arborSingle action potentialAxon initial segmentVoltage-gated sodiumProximal dendritesDendritic appendagesInhibitory neurotransmitterExcitatory inputsInhibitory interneuronsVoltage-sensitive dyeSynaptic inputsThalamocortical cellsCalcium transientsCalcium imagingNeurotransmitter releaseThe spatio‐temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study
Popovic MA, Foust AJ, McCormick DA, Zecevic D. The spatio‐temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study. The Journal Of Physiology 2011, 589: 4167-4187. PMID: 21669974, PMCID: PMC3180577, DOI: 10.1113/jphysiol.2011.209015.Peer-Reviewed Original ResearchConceptsSpike trigger zoneAction potential initiationAxon initial segmentTrigger zoneLayer 5 pyramidal neuronsPotential initiationLayer 5 pyramidal cellsMature axonsPyramidal neuronsAxonal collateralsPyramidal cellsNeuronal plasticityAction potentialsImmature axonsPotential imaging techniqueAxonsImmunocytochemical dataNeuronal computationSaltatory conductionAP propagationElectrophysiological measuresInitial segmentImaging techniquesCritical roleInitiation
2010
P/Q and N Channels Control Baseline and Spike-Triggered Calcium Levels in Neocortical Axons and Synaptic Boutons
Yu Y, Maureira C, Liu X, McCormick D. P/Q and N Channels Control Baseline and Spike-Triggered Calcium Levels in Neocortical Axons and Synaptic Boutons. Journal Of Neuroscience 2010, 30: 11858-11869. PMID: 20810905, PMCID: PMC2947942, DOI: 10.1523/jneurosci.2651-10.2010.Peer-Reviewed Original ResearchConceptsAxon initial segmentNeuronal excitabilityPyramidal cellsCalcium concentrationPresynaptic terminalsWhole-cell patch-clamp recordingsPrefrontal cortical pyramidal cellsOmega-agatoxin IVAOmega-conotoxin GVIACortical pyramidal cellsPatch-clamp recordingsBaseline calcium concentrationAction potential repolarizationAction potential generationNeocortical axonsVoltage-activated ion channelsCalcium currentCortical axonsSynaptic terminalsCalcium levelsCalcium channelsSynaptic boutonsSuprathreshold depolarizationElectrophysiological propertiesSubthreshold depolarizationAction Potentials Initiate in the Axon Initial Segment and Propagate through Axon Collaterals Reliably in Cerebellar Purkinje Neurons
Foust A, Popovic M, Zecevic D, McCormick DA. Action Potentials Initiate in the Axon Initial Segment and Propagate through Axon Collaterals Reliably in Cerebellar Purkinje Neurons. Journal Of Neuroscience 2010, 30: 6891-6902. PMID: 20484631, PMCID: PMC2990270, DOI: 10.1523/jneurosci.0552-10.2010.Peer-Reviewed Original ResearchConceptsAxon initial segmentAxon collateralsAction potentialsPurkinje neuronsComplex spikesLocal axon collateralsCerebellar Purkinje neuronsInitial segmentFast action potentialsAxon branch pointsSynaptic inputsVoltage-sensitive dyeCerebellar cortexNeuronal processingSpike initiationDischarge frequencySingle trialCollateralsOutput cellsNeurons
2008
Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics
Yu Y, Shu Y, McCormick DA. Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics. Journal Of Neuroscience 2008, 28: 7260-7272. PMID: 18632930, PMCID: PMC2664555, DOI: 10.1523/jneurosci.1613-08.2008.Peer-Reviewed Original ResearchConceptsAxon initial segmentAction potentialsAction potential backpropagationAction potential outputAction potential responsesThreshold variabilityInitial segmentCortical neuronsSynaptic activitySynaptic inputsSomatic recordingsCortical ensemblesSensorimotor integrationRate variabilityAction potential eventsSpike initiationAmplitude-time courseTime courseHigh rateTrial variabilityNeurons
2006
Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings
Shu Y, Duque A, Yu Y, Haider B, McCormick D. Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings. Journal Of Neurophysiology 2006, 97: 746-760. PMID: 17093120, DOI: 10.1152/jn.00922.2006.Peer-Reviewed Original ResearchConceptsCortical pyramidal cellsAction potential initiationAxon initial segmentPyramidal cellsAction potentialsSynaptic activityLayer 5 pyramidal neuronsSimultaneous whole-cell recordingsWhole-cell recordingsNeocortical pyramidal cellsRecurrent network activityAction potential generationInitial segmentIntradendritic injectionPyramidal neuronsApical dendritesEpileptiform activityCortical neuronsEpileptiform dischargesIntracortical axonsEpileptic seizuresSynaptic bombardmentCell recordingsDistal axonsSynaptic barrages
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