2025
Relative roles of HCN4 and synaptic excitation in pyramidal neuron firing rates in a hyperactive Rheb‐mTOR condition
Chatzikalymniou A, Getz S, Xu Y, Patel D, Soltesz I, Bordey A. Relative roles of HCN4 and synaptic excitation in pyramidal neuron firing rates in a hyperactive Rheb‐mTOR condition. Epilepsia 2025 PMID: 40512428, DOI: 10.1111/epi.18456.Peer-Reviewed Original ResearchFocal malformations of cortical developmentExcitatory postsynaptic currentsPyramidal neuronsExcitatory postsynaptic current amplitudeFiring rateMalformations of cortical developmentPyramidal cell excitabilityExcitatory synaptic inputsNeuronal firing rateAcute brain slicesSingle-cell computational modelingIncreased dendritic complexityCortical pyramidal neuronsConstitutively active RhebPostsynaptic currentsFocal malformationsSynaptic excitationNeuronal excitabilityMTOR pathway genesDe Novo somatic mutationsPostnatal dayCell excitabilityFetal developmentIncreased mTOR activitySynaptic inputsMeningeal lymphatics-microglia axis regulates synaptic physiology
Kim K, Abramishvili D, Du S, Papadopoulos Z, Cao J, Herz J, Smirnov I, Thomas J, Colonna M, Kipnis J. Meningeal lymphatics-microglia axis regulates synaptic physiology. Cell 2025, 188: 2705-2719.e23. PMID: 40120575, PMCID: PMC12086007, DOI: 10.1016/j.cell.2025.02.022.Peer-Reviewed Original ResearchConceptsBehavioral alterationsAging-associated cognitive declineMemory taskNeural mechanismsIL-6Cognitive declineIL-6-dependent mechanismInhibitory synaptic inputsCortical circuitryBehavioral changesMeningeal lymphaticsInterleukin-6 geneIL-6 signalingAge-associatedSynaptic inputsLymphatic dysfunctionLymphatic functionCerebrospinal fluidProlonged impairmentIncreased expressionNeurodegenerative conditionsLymphaticsPotential targetDysfunctionDeficitsOptic 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 excitabilityHigher-order thalamic input to cortex selectively conveys state information
Neske G, Cardin J. Higher-order thalamic input to cortex selectively conveys state information. Cell Reports 2025, 44: 115292. PMID: 39937647, PMCID: PMC11920878, DOI: 10.1016/j.celrep.2025.115292.Peer-Reviewed Original ResearchConceptsHigher-order thalamic nucleiHigher-order visual thalamusHigher-order thalamusCortical sensory processingCorticocortical communicationVisual thalamusImaging of neuronsMedial visual cortexStrong synaptic inputVisual cortexContextual signalsVisual informationCortical areasThalamic inputRelay of informationSynaptic inputsCorticocortical projectionsSensory peripheryThalamic nucleiCortical neuronsThalamocortical projectionsAxon terminalsOptogenetic manipulationNeocortical areasInformation
2024
Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites
Benedetti L, Fan R, Weigel A, Moore A, Houlihan P, Kittisopikul M, Park G, Petruncio A, Hubbard P, Pang S, Xu C, Hess H, Saalfeld S, Rangaraju V, Clapham D, De Camilli P, Ryan T, Lippincott-Schwartz J. Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites. Cell 2024, 188: 484-500.e22. PMID: 39708809, DOI: 10.1016/j.cell.2024.11.029.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum-plasma membrane junctionsEndoplasmic reticulum-plasma membranePlasma membrane of dendritesVoltage-gated Ca<sup>2+</sup> channelsER-plasma membrane junctionsMembrane of dendritesProtein kinase IIRyanodine receptorSynaptic inputsDendritic computationsSpine stimulationNeuronal dendritesKinase IIIntracellular signalingMembrane junctionsPlasma membraneER tubulesSignal propagationSignal transmissionSubcellular architectureRyanodineLadder-like arraysLocal activationReleaseDendritesCompartmentalized pooling generates orientation selectivity in wide-field amacrine cells
Lei W, Clark D, Demb J. Compartmentalized pooling generates orientation selectivity in wide-field amacrine cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2411130121. PMID: 39602271, PMCID: PMC11626119, DOI: 10.1073/pnas.2411130121.Peer-Reviewed Original ResearchConceptsOrientation selectivityBand-pass spatial frequency tuningVisual systemReceptive fieldsSpatial frequency tuningWide-field amacrine cellsReceptive field modelOrientation detectionKappa-opioid receptorsAmacrine cellsDetecting orientationVisual sceneFrequency tuningGlycinergic inhibitionOpioid receptorsField modelSpecific membrane resistanceExcitatory inputSynaptic inputsCalcium imagingMouse retinaCalcium signalingDendritic compartmentsMicrocircuit levelPolarization
2023
The cellular architecture of memory modules in Drosophila supports stochastic input integration
Hafez O, Escribano B, Ziegler R, Hirtz J, Niebur E, Pielage J. The cellular architecture of memory modules in Drosophila supports stochastic input integration. ELife 2023, 12: e77578. PMID: 36916672, PMCID: PMC10069864, DOI: 10.7554/elife.77578.Peer-Reviewed Original ResearchConceptsKenyon cellsDecision moduleEfficient storageComputational principlesMushroom bodiesMB output neuronsPatch-clamp recordingsSpiking behaviorOutput neuronsMemory modulesInput integrationOdor inputSynaptic inputsStochastic connectionsArchitectureSynaptic localizationSynaptic connectionsDecision makingComputational modelInputMemoryNeuronsCellular architectureValenced informationModulation
2021
Dopaminergic mechanism underlying reward-encoding of punishment omission during reversal learning in Drosophila
McCurdy LY, Sareen P, Davoudian PA, Nitabach MN. Dopaminergic mechanism underlying reward-encoding of punishment omission during reversal learning in Drosophila. Nature Communications 2021, 12: 1115. PMID: 33602917, PMCID: PMC7893153, DOI: 10.1038/s41467-021-21388-w.Peer-Reviewed Original ResearchConceptsDopaminergic neuronsCholinergic neuronsNeural circuit mechanismsCholinergic relayDopaminergic mechanismsSynaptic excitationSynaptic reconstructionSynaptic inputsVivo functional imagingCircuit mechanismsNeuronsAversive memoryFunctional imagingOdor responsesAversive outcomesReduced activationSuch activationCircuit motifsActivationOutcomesElectric shock punishmentSensory cuesUnexpected omissionShock punishmentBehavioral analysis
2020
Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines
Ali F, Gerhard DM, Sweasy K, Pothula S, Pittenger C, Duman RS, Kwan AC. Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines. Nature Communications 2020, 11: 72. PMID: 31911591, PMCID: PMC6946708, DOI: 10.1038/s41467-019-13809-8.Peer-Reviewed Original ResearchConceptsDendritic spinesN-methyl-D-aspartate receptor antagonistPrefrontal cortexPrefrontal dendritic spinesApical dendritic spinesSomatostatin-expressing (SST) interneuronsCortico-cortical connectivityElevated calcium levelsMedial prefrontal cortexKetamine actsAntidepressant effectsGABAergic neuronsSST interneuronsKetamine actionPyramidal neuronsNMDAR antagonismReceptor antagonistSubanesthetic ketamineSubanesthetic doseDendritic inhibitionAwake miceCortical interneuronsSynaptic inputsCalcium levelsCalcium transients
2019
GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex
Duan Z, Che A, Chu P, Modol L, Bollmann Y, Babij R, Fetcho R, Otsuka T, Fuccillo M, Liston C, Pisapia D, Cossart R, De Marco García N. GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex. Neuron 2019, 105: 75-92.e5. PMID: 31780329, PMCID: PMC6982374, DOI: 10.1016/j.neuron.2019.10.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell SurvivalExcitatory Postsynaptic PotentialsFemaleGABAergic Neuronsgamma-Aminobutyric AcidInhibitory Postsynaptic PotentialsInterneuronsMaleMedian EminenceMembrane PotentialsMiceMice, TransgenicNeural PathwaysNeurogenesisParvalbuminsPyramidal CellsSomatosensory CortexSomatostatinSynaptic PotentialsConceptsPyramidal cellsGanglionic eminenceReduction of GABA releaseIncreased network synchronyAssembly of neuronal circuitsEffects of GABAMedial ganglionic eminenceCaudal ganglionic eminenceSpontaneous activity patternsGABA releaseInterneuron survivalPostnatal daySomatostatin interneuronsNeonatal developmentMouse pupsSynaptic inputsCalcium imagingInterneuronsDeveloping cortexIncreased survivalNeuronal circuitsSomatosensory cortexAberrant patternsNetwork synchronySensory cortexMolecular layer interneurons shape the spike activity of cerebellar Purkinje cells
Brown A, Arancillo M, Lin T, Catt D, Zhou J, Lackey E, Stay T, Zuo Z, White J, Sillitoe R. Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells. Scientific Reports 2019, 9: 1742. PMID: 30742002, PMCID: PMC6370775, DOI: 10.1038/s41598-018-38264-1.Peer-Reviewed Original ResearchConceptsMolecular layer interneuronsPurkinje cellsGABAergic neurotransmissionSpike firingVesicular GABA transporterClasses of interneuronsPurkinje cell functionCerebellar Purkinje cellsComplex spike firingPurkinje cell activityPurkinje cell simple spike firingInhibitory molecular layer interneuronsConditional genetic approachPurkinje cell simple spikesSynaptic inputsStellate cellsSpike activitySimple spike firingFiring propertiesGABA transporterCell activityInterneuronsSelective depletionCell functionComplex spikes
2018
Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus
James SD, Hawkins VE, Falquetto B, Ruskin DN, Masino SA, Moreira TS, Olsen ML, Mulkey DK. Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus. ENeuro 2018, 5: eneuro.0404-18.2018. PMID: 30627640, PMCID: PMC6325544, DOI: 10.1523/eneuro.0404-18.2018.Peer-Reviewed Original ResearchMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAdenosineAnimalsAnimals, NewbornBariumCarbon DioxideChemoreceptor CellsExcitatory Amino Acid AntagonistsFemaleMaleMice, Inbred C57BLMice, TransgenicNeuronal PlasticityNeurotransmitter AgentsPotassium Channel BlockersPurinergic AgentsRatsRats, Sprague-DawleyReceptors, Purinergic P1Respiratory CenterSignal TransductionSodium Channel BlockersTetrodotoxinConceptsChemosensitive RTN neuronsRTN neuronsA1 receptorsRTN chemoreceptorsChemoreceptor activitySelective A1 receptor antagonistFrequency of EPSCsWild-type mouse pupsA1 receptor antagonistExcitatory synaptic inputsReceptor-dependent mechanismEffects of adenosineSubset of neuronsCell-attached recordingsLike conductanceRTN chemoreceptionChemosensitive neuronsRetrotrapezoid nucleusReceptor antagonistSynaptic mechanismsMouse pupsSynaptic inputsRespiratory chemoreceptorsPurinergic signalingPurinergic regulation
2017
The 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
Divisive suppression explains high-precision firing and contrast adaptation in retinal ganglion cells
Cui Y, Wang YV, Park SJ, Demb JB, Butts DA. Divisive suppression explains high-precision firing and contrast adaptation in retinal ganglion cells. ELife 2016, 5: e19460. PMID: 27841746, PMCID: PMC5108594, DOI: 10.7554/elife.19460.Peer-Reviewed Original ResearchConceptsExcitatory synaptic inputsSynaptic inputsGanglion cell functionContrast adaptationRetinal ganglion cellsGanglion cell inputsComplex neural circuitsGanglion cell outputCell-intrinsic mechanismsGanglion cellsDivisive interactionMouse retinaNeural circuitsSpike responsesCell functionDivisive suppressionSensory processingCell inputSpike generation mechanismMillisecond precisionVisual processingSpike trainsCell outputSuppressionRetinaDistinct 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 PeptideMitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus
Varela L, Schwartz ML, Horvath TL. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus. Neurobiology Of Disease 2016, 90: 68-74. PMID: 26777666, DOI: 10.1016/j.nbd.2016.01.004.Peer-Reviewed Original ResearchConceptsHippocampal neuronsMitochondria-endoplasmic reticulum interactionUCP2-KO miceEarly postnatal exposureLoss of synapsesOxygen tensionHigher brain regionsAdaptive mitochondrial responsesProtein 2 expressionHypothalamic circuitsPostnatal exposureKO miceSynaptic remodelingSystemic metabolismSynaptic inputsBrain cellsMetabolic controlNeuronal mitochondriaBrain regionsAdaptive responseNeuronsHippocampusMitochondrial dynamicsMetabolic challengesCortex
2015
Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons
Nikolaev Y, Dosen P, Laver D, van Helden D, Hamill O. Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons. Brain Research 2015, 1608: 1-13. PMID: 25765154, DOI: 10.1016/j.brainres.2015.02.051.Peer-Reviewed Original ResearchConceptsHippocampal pyramidal neuronsPyramidal neuronsChannel currentsSpike activityAction potentialsRhythmic spike activityCell-attached patch recordingsTraumatic brain injuryCerebellar Purkinje neuronsMouse brain slicesCation channel currentsCentral neuronsBrain injuryLocus coeruleusBrain slicesSynaptic inputsVoltage-gated channelsPurkinje neuronsPatch recordingsInward currentsMammalian brainNeuron typesNeuronsMechanosensitive organCation channelsLow circulating levels of bisphenol‐A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys
Elsworth JD, Jentsch JD, Groman SM, Roth RH, Redmond ED, Leranth C. Low circulating levels of bisphenol‐A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys. The Journal Of Comparative Neurology 2015, 523: 1248-1257. PMID: 25557059, PMCID: PMC4390445, DOI: 10.1002/cne.23735.Peer-Reviewed Original ResearchConceptsLevels of BPARegimen of exposureAdult male vervet monkeysExcitatory synaptic inputsAsymmetric spine synapsesAdult male monkeysImpact of BPADorsolateral prefrontal cortexPyramidal neuronsSpine synapsesSynaptic effectsCognitive dysfunctionMale vervet monkeysSynaptic inputsDendritic spinesPrimate brainExposure of humansMale monkeysBrain regionsCognitive deficitsLevels of bisphenolPrefrontal cortexAdverse effectsManufacture of plasticsStudies of humans
2014
Activity-Dependent Regulation of Dendritic Complexity by Semaphorin 3A through Farp1
Cheadle L, Biederer T. Activity-Dependent Regulation of Dendritic Complexity by Semaphorin 3A through Farp1. Journal Of Neuroscience 2014, 34: 7999-8009. PMID: 24899721, PMCID: PMC4044256, DOI: 10.1523/jneurosci.3950-13.2014.Peer-Reviewed Original ResearchConceptsDendritic complexityTotal dendritic branch lengthActivity-dependent regulationDendritic shaftsDendritic arborizationDendritic arborsHippocampal neuronsSynaptic inputsNeuronal activityRat neuronsSemaphorin 3ANeuronal structuresSema3ADendrite differentiationNeuronsRac1 activatorDendritic morphologyComplex neuronal structuresPlexinA1Soluble cuesSignaling proteinsArborizationFARP1CoreceptorExcitatory Synaptic Inputs to Mouse On-Off Direction-Selective Retinal Ganglion Cells Lack Direction Tuning
Park SJ, Kim IJ, Looger LL, Demb JB, Borghuis BG. Excitatory Synaptic Inputs to Mouse On-Off Direction-Selective Retinal Ganglion Cells Lack Direction Tuning. Journal Of Neuroscience 2014, 34: 3976-3981. PMID: 24623775, PMCID: PMC3951696, DOI: 10.1523/jneurosci.5017-13.2014.Peer-Reviewed Original ResearchConceptsDirection-selective ganglion cellsOFF direction-selective ganglion cellsStarburst amacrine cellsGlutamate releaseBipolar cellsExcitatory currentsPreferred direction motionBipolar cell typesExcitatory synaptic inputsNull-direction inhibitionGABA-A receptorsWhole-cell recordingsNull-direction motionDSGC dendritesGABA releaseCholinergic inputAmacrine cellsGanglion cellsSynaptic mechanismsSynaptic inputsMammalian retinaMouse retinaIntensity-based glutamate-sensing fluorescent reporterDirection selectivityDirection tuning
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