2023
Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat
Lee H, Weinberg-Wolf H, Lee H, Lee T, Conte J, Godoy-Parejo C, Demb J, Rudenko A, Kim IJ. Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat. PLOS Biology 2023, 21: e3002386. PMID: 37983249, PMCID: PMC10695396, DOI: 10.1371/journal.pbio.3002386.Peer-Reviewed Original ResearchConceptsTranscription factor Brn3bLoss of neuronsVisual threatLateral posterior nucleusMutant mice displayDefensive responsesDefensive freezing responsesPosterior nucleusTachykinin 2Mice displayMidbrain circuitVisual circuitsNeural circuitryBrn3bSpecific genetic componentsFreezing responseFear-associated behaviorsSocial isolationTac2Behavioral phenotypesMolecular mechanismsFunctional organizationGenetic componentResponseSimilar mechanism
2021
Preservation of vision after CaMKII-mediated protection of retinal ganglion cells
Guo X, Zhou J, Starr C, Mohns EJ, Li Y, Chen EP, Yoon Y, Kellner CP, Tanaka K, Wang H, Liu W, Pasquale LR, Demb JB, Crair MC, Chen B. Preservation of vision after CaMKII-mediated protection of retinal ganglion cells. Cell 2021, 184: 4299-4314.e12. PMID: 34297923, PMCID: PMC8530265, DOI: 10.1016/j.cell.2021.06.031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrainCalcium-Calmodulin-Dependent Protein Kinase Type 2Cyclic AMP Response Element-Binding ProteinCytoprotectionDependovirusDisease Models, AnimalEnzyme ActivationGlaucomaMice, Inbred C57BLNeurotoxinsOptic Nerve InjuriesRetinal Ganglion CellsSignal TransductionVision, OcularConceptsRetinal ganglion cellsRGC survivalRGC somataGanglion cellsDiverse insultsRGC axon projectionOptic nerve injurySole output neuronsPreservation of visionElevated intraocular pressureIrreversible vision lossPathological statesExcitotoxic injuryNerve injuryGlaucoma modelIntraocular pressureRGC axonsVision lossVisual functionNormal retinaVisual cortexAxon projectionsGenetic deficiencyInjuryRetinaPhotoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina
Pottackal J, Walsh HL, Rahmani P, Zhang K, Justice NJ, Demb JB. Photoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina. Journal Of Neuroscience 2021, 41: 1489-1504. PMID: 33397711, PMCID: PMC7896016, DOI: 10.1523/jneurosci.0674-20.2020.Peer-Reviewed Original ResearchMeSH KeywordsAmacrine CellsAnimalsCorticotropin-Releasing HormoneElectrophysiological PhenomenaExcitatory Postsynaptic PotentialsFemaleGamma-Aminobutyric AcidGap JunctionsMaleMiceMice, Inbred C57BLNeural InhibitionNeuronsOptogeneticsPhotoreceptor Cells, VertebrateRetinaRetinal Cone Photoreceptor CellsRetinal Ganglion CellsRetinal Rod Photoreceptor CellsRod OpsinsSynapsesConceptsGap junction-mediated electrical synapsesAmacrine cellsElectrical synapsesIpRGC activityGanglion cellsRetinal interneuronsRetinal circuitsPhotosensitive retinal ganglion cellsGABAergic amacrine cellsRetinal ganglion cellsWhole-cell recordingsSpecific RGC typesAbsence of rodsIpRGC typesRGC typesPharmacological blockadeRetinal neuronsMelanopsin expressionMature retinaMouse retinaSynaptic circuitsNeuronal circuitsInterneuronsOptogenetic stimulationLocal inhibition
2020
Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision
Park SJ, Lieberman EE, Ke JB, Rho N, Ghorbani P, Rahmani P, Jun NY, Lee HL, Kim IJ, Briggman KL, Demb JB, Singer JH. Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision. ELife 2020, 9: e56077. PMID: 32412412, PMCID: PMC7228767, DOI: 10.7554/elife.56077.Peer-Reviewed Original ResearchConceptsAII amacrine cellsProjection neuronsSingle interneuron typeConnectomic analysisBipolar cell pathwaysNovel neural circuitGABAergic cellsAmacrine cellsCentral neuronsGanglion cellsSynaptic layersRetinal circuitsInterneuron typesSurround inhibitionMouse retinaNight visionON responseExcitatory centerOptogenetic analysesNeural circuitsInhibitory surroundCell pathwaysRod photoreceptorsReceptive fieldsRb pathway
2018
Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
Yao K, Qiu S, Wang YV, Park SJH, Mohns EJ, Mehta B, Liu X, Chang B, Zenisek D, Crair MC, Demb JB, Chen B. Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas. Nature 2018, 560: 484-488. PMID: 30111842, PMCID: PMC6107416, DOI: 10.1038/s41586-018-0425-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninBlindnessCell CycleCell ProliferationCellular ReprogrammingDisease Models, AnimalFemaleGTP-Binding Protein alpha SubunitsHeterotrimeric GTP-Binding ProteinsMaleMiceNeurogenesisNeurogliaRegenerative MedicineRetinal Rod Photoreceptor CellsStem CellsTranscription FactorsTransducinVisual CortexVisual PathwaysConceptsMüller gliaGene transferMG proliferationRod photoreceptorsMammalian retinaCell fate specificationPopulations of stemSubsequent gene transferFate specificationRetinal stem cellsTranscription factorsRetinal neuronsCell cycleDouble mutant miceRegenerative machineryDe novo genesisΒ-cateninStem cellsProgenitor cellsRestoration of visionPrimary visual cortexMutant miceAbsence of injuryPhotoreceptorsRetinal injuryConvergence and Divergence of CRH Amacrine Cells in Mouse Retinal Circuitry
Park SJH, Pottackal J, Ke JB, Jun NY, Rahmani P, Kim IJ, Singer JH, Demb JB. Convergence and Divergence of CRH Amacrine Cells in Mouse Retinal Circuitry. Journal Of Neuroscience 2018, 38: 3753-3766. PMID: 29572434, PMCID: PMC5895998, DOI: 10.1523/jneurosci.2518-17.2018.Peer-Reviewed Original ResearchConceptsAlpha ganglion cellsGanglion cell typesAmacrine cellsGanglion cellsCRH cellsAlpha cellsGABAergic synapsesInhibitory interneuronsExcitation/inhibition balanceCorticotropin-releasing hormoneCre transgenic miceFire action potentialsTonic excitatory driveCell typesBalance of excitationGABA releaseExcitatory circuitsRetinal circuitryExcitatory driveInhibition balanceInhibitory inputsMammalian retinaMouse retinaAction potentialsOptogenetic analyses
2017
Selective synaptic connections in the retinal pathway for night vision
Beaudoin DL, Kupershtok M, Demb JB. Selective synaptic connections in the retinal pathway for night vision. The Journal Of Comparative Neurology 2017, 527: 117-132. PMID: 28856684, PMCID: PMC5832573, DOI: 10.1002/cne.24313.Peer-Reviewed Original ResearchConceptsAII amacrine cellsRetinal ganglion cellsAmacrine cellsRGC typesBipolar terminalsSynaptic connectionsCertain retinal ganglion cellsConnected retinal ganglion cellsIonotropic glutamate receptor antagonistsOFF alpha cellsGlutamate receptor antagonistsInner plexiform layerBipolar cell terminalsSelective synaptic connectionsBipolar cell activityOFF alphaRetinal connectionsRetinal pathwaysPlexiform layerReceptor antagonistDirect synapsesGanglion cellsGlycinergic synapsesInhibitory currentsMammalian retinaThese retinas are made for walkin'
Demb JB, Clark DA. These retinas are made for walkin'. Nature 2017, 546: 476-477. PMID: 28607483, DOI: 10.1038/nature22505.Peer-Reviewed Original Research
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 outputSuppressionRetinaParallel Computations in Insect and Mammalian Visual Motion Processing
Clark DA, Demb JB. Parallel Computations in Insect and Mammalian Visual Motion Processing. Current Biology 2016, 26: r1062-r1072. PMID: 27780048, PMCID: PMC5108051, DOI: 10.1016/j.cub.2016.08.003.Peer-Reviewed Original ResearchComplexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses
Mortensen LS, Park SJ, Ke JB, Cooper BH, Zhang L, Imig C, Löwel S, Reim K, Brose N, Demb JB, Rhee JS, Singer JH. Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses. Cell Reports 2016, 15: 2239-2250. PMID: 27239031, PMCID: PMC5134263, DOI: 10.1016/j.celrep.2016.05.012.Peer-Reviewed Original ResearchConceptsRod bipolarsAsynchronous releaseAmacrine cell synapsesRetinal ganglion cellsRetinal pathwaysGanglion cellsCell synapsesRetinal circuitsRibbon synapsesMouse retinaMultivesicular releaseNeural circuitsComplexin proteinsSynapsesCircuit functionCplx3SignalingStudy linksReleaseExocytosisRB outputRetinaMolecular features distinguish ten neuronal types in the mouse superficial superior colliculus
Byun H, Kwon S, Ahn HJ, Liu H, Forrest D, Demb JB, Kim IJ. Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus. The Journal Of Comparative Neurology 2016, 524: 2300-2321. PMID: 26713509, PMCID: PMC4892959, DOI: 10.1002/cne.23952.Peer-Reviewed Original ResearchConceptsSpecific cell typesCell typesMolecular markersEts variant gene 1Distinct expression patternsSuperior colliculusMouse SSCsTranscription factorsCadherin-7Retinoid-related orphan receptor βContactin-3Cell adhesion moleculeProtein 3BNeuronal typesSSC neuronsExpression patternsGene expressionMolecular mechanismsProtocadherin 20Gene 1Binding proteinCadherin-6Netrin-G2Calcium binding proteinMolecular families
2015
Function and Circuitry of VIP+ Interneurons in the Mouse Retina
Park SJ, Borghuis BG, Rahmani P, Zeng Q, Kim IJ, Demb JB. Function and Circuitry of VIP+ Interneurons in the Mouse Retina. Journal Of Neuroscience 2015, 35: 10685-10700. PMID: 26224854, PMCID: PMC4518048, DOI: 10.1523/jneurosci.0222-15.2015.Peer-Reviewed Original ResearchConceptsGanglion cell layerAmacrine cell typesInner nuclear layerAmacrine cellsGanglion cellsINL cellsON pathwayGanglion cell dendritesGanglion cell typesBipolar cell terminalsWhole-cell recordingsCell typesNervous system functionSpatial tuningBipolar cell pathwaysTransgenic mouse lineGCL cellsOptic nerveGABAergic interneuronsRetinal functionCell dendritesRetinal circuitryInhibitory interneuronsNuclear layerBipolar interneurons
2014
NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells
Stafford BK, Manookin MB, Singer JH, Demb JB. NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells. The Journal Of Physiology 2014, 592: 4877-4889. PMID: 25217374, PMCID: PMC4259533, DOI: 10.1113/jphysiol.2014.276543.Peer-Reviewed Original ResearchConceptsGanglion cellsNMDAR kineticsOFF alphaMammalian retinal ganglion cellsNMDA-type glutamate receptorsAMPAR-mediated responsesOFF alpha cellsGanglion cell typesRetinal ganglion cellsGuinea pig retinaNMDAR-mediated responsesBipolar cell pathwaysCell typesFast excitatory neurotransmissionGlutamatergic transmissionPresynaptic inhibitionGlutamate releaseSame synapsesSynaptic inhibitionGlutamate receptorsHz stimulationPostsynaptic AMPAExcitatory neurotransmissionSensory neuronsAMPA receptorsKainate Receptors Mediate Signaling in Both Transient and Sustained OFF Bipolar Cell Pathways in Mouse Retina
Borghuis BG, Looger LL, Tomita S, Demb JB. Kainate Receptors Mediate Signaling in Both Transient and Sustained OFF Bipolar Cell Pathways in Mouse Retina. Journal Of Neuroscience 2014, 34: 6128-6139. PMID: 24790183, PMCID: PMC4004803, DOI: 10.1523/jneurosci.4941-13.2014.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDrug InteractionsExcitatory Amino Acid AntagonistsFemaleGlutamic AcidHexamethoniumIn Vitro TechniquesLightMaleMiceMice, Inbred C57BLNicotinic AntagonistsPatch-Clamp TechniquesPhotic StimulationPropionatesReceptors, Kainic AcidRetinaRetinal Bipolar CellsSignal TransductionVisual PathwaysConceptsGlutamate releaseBipolar cellsCone bipolar cell typesOFF bipolar cell pathwaysMouse bipolar cellsGanglion cell dendritesKainate-type glutamate receptorsBipolar cell typesLight-evoked responsesBipolar cell pathwaysGanglion cellsOFF layerCell dendritesReceptor mediatesGlutamate receptorsKainate receptorsAMPA receptorsTwo-photon imagingMouse retinaBipolar pathwayIntact circuitsOFF pathwaysElectrophysiological recordingsCircuit mechanismsReceptorsExcitatory 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 tuningDevelopmental Changes in NMDA Receptor Subunit Composition at ON and OFF Bipolar Cell Synapses onto Direction-Selective Retinal Ganglion Cells
Stafford BK, Park SJ, Wong KY, Demb JB. Developmental Changes in NMDA Receptor Subunit Composition at ON and OFF Bipolar Cell Synapses onto Direction-Selective Retinal Ganglion Cells. Journal Of Neuroscience 2014, 34: 1942-1948. PMID: 24478373, PMCID: PMC3905152, DOI: 10.1523/jneurosci.4461-13.2014.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornExcitatory Amino Acid AgonistsFemaleGene Expression Regulation, DevelopmentalGlutamic AcidGreen Fluorescent ProteinsIn Vitro TechniquesLightMaleMembrane PotentialsMiceMice, Inbred C57BLMice, TransgenicNeurotransmitter AgentsN-MethylaspartatePatch-Clamp TechniquesReceptors, N-Methyl-D-AspartateRetinaRetinal Bipolar CellsRetinal Ganglion CellsSynapsesVisual PathwaysConceptsNMDA-type glutamate receptorsDirection-selective ganglion cellsExtrasynaptic NMDA-type glutamate receptorsNMDAR-mediated responsesBipolar cell synapsesGanglion cellsCell synapsesMature retinaSpecific ganglion cell typesDirection-selective retinal ganglion cellsNMDA receptor subunit compositionActivity-dependent synaptic developmentBipolar cell inputsGanglion cell typesRetinal ganglion cellsFirst postnatal monthReceptor subunit compositionWhole-cell recordingsGlutamatergic synapse formationCell typesGluN2B antagonist ifenprodilReceptor blockadeGlutamate releaseBipolar synapsesGlutamatergic synapses
2013
Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses
Ke JB, Wang YV, Borghuis BG, Cembrowski MS, Riecke H, Kath WL, Demb JB, Singer JH. Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses. Neuron 2013, 81: 388-401. PMID: 24373883, PMCID: PMC4267681, DOI: 10.1016/j.neuron.2013.10.054.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerateAdaptation, OcularAnimalsBiophysicsComputer SimulationExcitatory Amino Acid AntagonistsGlucosamine 6-Phosphate N-AcetyltransferaseGreen Fluorescent ProteinsIn Vitro TechniquesLightMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, NeurologicalPatch-Clamp TechniquesQuinoxalinesRetinal Bipolar CellsRetinal Rod Photoreceptor CellsSynapsesVisual PathwaysTwo-Photon Imaging of Nonlinear Glutamate Release Dynamics at Bipolar Cell Synapses in the Mouse Retina
Borghuis BG, Marvin JS, Looger LL, Demb JB. Two-Photon Imaging of Nonlinear Glutamate Release Dynamics at Bipolar Cell Synapses in the Mouse Retina. Journal Of Neuroscience 2013, 33: 10972-10985. PMID: 23825403, PMCID: PMC3718381, DOI: 10.1523/jneurosci.1241-13.2013.Peer-Reviewed Original ResearchConceptsInner plexiform layerGanglion cellsPlexiform layerY-type retinal ganglion cellsY-type ganglion cellsPresynaptic bipolar cellsBipolar cell outputBipolar cell synapsesRetinal ganglion cellsWhole-cell recordingsPostsynaptic ganglion cellsIntact neural circuitsReceptive field propertiesPresynaptic release sitesBipolar terminalsGlutamate releaseGlutamate synapsesSynaptic basisCell synapsesBipolar cellsExcitatory currentsSurround inhibitionMouse retinaTwo-photon imagingIndependent releaseAn optimized fluorescent probe for visualizing glutamate neurotransmission
Marvin JS, Borghuis BG, Tian L, Cichon J, Harnett MT, Akerboom J, Gordus A, Renninger SL, Chen TW, Bargmann CI, Orger MB, Schreiter ER, Demb JB, Gan WB, Hires SA, Looger LL. An optimized fluorescent probe for visualizing glutamate neurotransmission. Nature Methods 2013, 10: 162-170. PMID: 23314171, PMCID: PMC4469972, DOI: 10.1038/nmeth.2333.Peer-Reviewed Original ResearchAnimalsAstrocytesBiosensing TechniquesCaenorhabditis elegansCalcium SignalingEscherichia coli ProteinsExcitatory Postsynaptic PotentialsFluorescent DyesGlutamic AcidGreen Fluorescent ProteinsHippocampusMiceMotor CortexNeuronsPhotic StimulationPyramidal CellsRecombinant Fusion ProteinsRetinaSignal-To-Noise RatioSynaptic TransmissionZebrafish