Jonathan Demb, PhD
Professor of Ophthalmology and Visual ScienceCards
Appointments
Contact Info
About
Titles
Professor of Ophthalmology and Visual Science
Biography
Jonathan Demb is a Professor in the Department of Ophthalmology & Visual Science with secondary appointments in the Department of Cellular & Molecular Physiology and the Department of Neuroscience. Dr. Demb obtained his doctoral degree from Stanford University and did postdoctoral training at the University of Pennsylvania. Demb was a faculty member at the University of Michigan before moving to Yale in 2011.
The Demb lab investigates the cellular and synaptic mechanisms that enable visual processing by the mammalian retina. Major accomplishments include identifying fundamental nonlinearities at retinal synapses that mediate specialized spatial processing by retinal ganglion cells; elucidating the role of disinhibition in visual contrast processing; characterizing asymmetries between the retina's ON and OFF pathways; determining roles of NMDA-type glutamate receptors in ganglion cell receptive fields; identifying characteristic properties of cone-mediated vision in the mouse retina; developing the use of a glutamate sensor (iGluSnFR) for study of retinal circuitry; identifying novel amacrine cell circuits using optogenetic technology; and testing experimental therapies in mouse models of retinal disease. Demb is a Reviewing Editor at the Journal of Neuroscience and is on the Editorial Board of PLoS Biology. He was awarded the Cogan Award in 2013 from the Associate for Research in Vision and Ophthalmology (ARVO) to recognize his contributions to the field of retinal neuroscience.
Appointments
Ophthalmology
ProfessorPrimaryCellular & Molecular Physiology
ProfessorSecondaryNeuroscience
ProfessorSecondary
Other Departments & Organizations
- Cellular & Molecular Physiology
- Interdepartmental Neuroscience Program
- Molecular Medicine, Pharmacology, and Physiology
- Neuroscience
- Neuroscience Track
- Ophthalmology
- Swartz Program in Theoretical Neurobiology
- Wu Tsai Institute
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- Postdoctoral Researcher
- University of Pennsylvania (2003)
- PhD
- Stanford University (1997)
- BA
- Boston University (1993)
Research
Overview
Current projects include: optogenetic techniques to define new interneuron circuits in the retina; optical imaging of neurotransmitter release in retinal circuitry; elucidating the role of NMDA receptors in visual processing; cellular basis of visual adaptation; mechanisms of retinal disease.
Medical Subject Headings (MeSH)
ORCID
0000-0003-2227-9041
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
In-Jung Kim, PhD
Pouyan Rahmani
Michael Crair, PhD
Damon Clark, PhD
Kathy Zhang
Retinal Ganglion Cells
Synapses
Retinal Bipolar Cells
Retinal Cone Photoreceptor Cells
Adaptation, Physiological
Publications
2024
Specific retinal neurons regulate context-dependent defensive responses to visual threat
Lee T, Weinberg-Wolf H, Zapadka T, Rudenko A, Demb J, Kim I. Specific retinal neurons regulate context-dependent defensive responses to visual threat. PNAS Nexus 2024, 3: pgae423. PMID: 39359403, PMCID: PMC11443969, DOI: 10.1093/pnasnexus/pgae423.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsBehavioral responsesRetinal ganglion cell typesVisual threatAlpha retinal ganglion cellsLooming stimuliThreatening stimuliMature miceGanglion cellsBehavioral reactionsUnique contributionsCell ablationVisual pathwayOutput neuronsEarly visual pathwayStimuliContextual signalsDefense responsesAerial predatorsEnvironmental contextThe Structural and Functional Integrity of Rod Photoreceptor Ribbon Synapses Depends on Redundant Actions of Dynamins 1 and 3
Hanke-Gogokhia C, Zapadka T, Finkelstein S, Klingeborn M, Maugel T, Singer J, Arshavsky V, Demb J. The Structural and Functional Integrity of Rod Photoreceptor Ribbon Synapses Depends on Redundant Actions of Dynamins 1 and 3. Journal Of Neuroscience 2024, 44: e1379232024. PMID: 38641407, PMCID: PMC11209669, DOI: 10.1523/jneurosci.1379-23.2024.Peer-Reviewed Original ResearchCitationsConceptsRod ribbon synapsesDynamin-1Photoreceptor ribbon synapsesDynamin isoformsMembrane scissionRibbon synapsesConventional synapsesReduced synaptic vesicle densitySynaptic vesicle recycling processesEndocytosis of synaptic vesiclesRibbon-type active zonesVesicle densityConditional gene knockout approachGene knockout approachSynaptic vesicle densityVesicle endocytosisVesicle cycleDisrupt endocytosisDynaminSpecialized proteinsSynapse integrityEnlarged vesiclesSynaptic vesiclesKnockout approachRod photoreceptors
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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTranscription 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
Computational and Molecular Properties of Starburst Amacrine Cell Synapses Differ With Postsynaptic Cell Type
Pottackal J, Singer JH, Demb JB. Computational and Molecular Properties of Starburst Amacrine Cell Synapses Differ With Postsynaptic Cell Type. Frontiers In Cellular Neuroscience 2021, 15: 660773. PMID: 34381333, PMCID: PMC8351878, DOI: 10.3389/fncel.2021.660773.Peer-Reviewed Original ResearchCitationsAltmetricPreservation 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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
Receptoral Mechanisms for Fast Cholinergic Transmission in Direction-Selective Retinal Circuitry
Pottackal J, Singer JH, Demb JB. Receptoral Mechanisms for Fast Cholinergic Transmission in Direction-Selective Retinal Circuitry. Frontiers In Cellular Neuroscience 2020, 14: 604163. PMID: 33324168, PMCID: PMC7726240, DOI: 10.3389/fncel.2020.604163.Peer-Reviewed Original ResearchCitationsConceptsDirection-selective ganglion cellsStarburst amacrine cellsFast cholinergic transmissionGABAergic inhibitionCholinergic transmissionGABAergic transmissionCholinergic excitationPostsynaptic currentsSynaptic mechanismsConventional synaptic transmissionReceptoral mechanismsReceptor blockadeAmacrine cellsGanglion cellsRetinal circuitryParacrine natureSynaptic transmissionConventional synapsesMammalian retinaMouse retinaParacrine transmissionParacrine modeDirection selectivityDistinct temporal propertiesReceptor kineticsConnectomic 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAII 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 injuryMelanopsin Shows Its (Contrast-)Sensitive Side
Pottackal J, Demb JB. Melanopsin Shows Its (Contrast-)Sensitive Side. Neuron 2018, 99: 630-632. PMID: 30138585, DOI: 10.1016/j.neuron.2018.08.007.Peer-Reviewed Original ResearchCitationsAltmetric
Academic Achievements & Community Involvement
activity NIH
Peer Review Groups and Grant Study SectionsReviewerDetailsStudy sections, ad hoc2010 - Presentactivity Journal of Neuroscience
Journal ServiceEditorDetailsReviewing Editor2016 - Presentactivity PLoS Biology
Journal ServiceEditorDetailsEditorial Board02/01/2017 - Presentactivity Board of Scientific Counselors
Advisory BoardsCouncil MemberDetailsNational Eye Institute06/01/2020 - Presentactivity Journal of Neuroscience
Journal ServiceEditorDetailsAssociate Editor2008 - 2013
News & Links
Media
- Stimulating the in vitro retina with visual contrast in a 'Y' shape evokes glutamate release from bipolar cell axon terminals in the same 'Y' shape, imaged with the glutamate sensor iGluSnFR (from Borghuis et al., 2013).
- Retinal ganglion cell filled with a fluorescent dye after whole-cell patch clamp recording.