2025
Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13: rp103620. PMID: 40488445, PMCID: PMC12148328, DOI: 10.7554/elife.103620.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentSchizophreniaImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorAstrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain
Tyurikova O, Kopach O, Zheng K, Rathore D, Codadu N, Wu S, Shen Y, Campbell R, Wykes R, Volynski K, Savtchenko L, Rusakov D. Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain. Cell Reports 2025, 44: 115299. PMID: 39951378, DOI: 10.1016/j.celrep.2025.115299.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBrainCalciumGlutamic AcidMaleMiceMice, Inbred C57BLPotassiumPotassium Channels, Inwardly RectifyingSynapsesSynaptic TransmissionConceptsKir4.1 channelsExtracellular potassiumInducing long-term synaptic potentiationHigh-frequency afferent stimulationLong-term synaptic potentiationPresynaptic Ca<sup>2+</sup> entryCortical spreading depolarizationKir4.1 levelsExcitatory transmissionSynaptic potentialsAfferent stimulationExcitatory synapsesGlutamate uptakePotassium homeostasisSpreading depolarizationPotassium levelsRelease probabilityAstrocytic mechanismsAstrocytesHigh potassiumKir4.1Brain circuitsSynapsesBrainMolecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse
Hanke-Gogokhia C, Zapadka T, Finkelstein S, Arshavsky V, Demb J. Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse. Advances In Experimental Medicine And Biology 2025, 1468: 325-330. PMID: 39930217, DOI: 10.1007/978-3-031-76550-6_54.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndocytosisExocytosisHumansMiceRetinal Rod Photoreceptor CellsSynapsesSynaptic TransmissionSynaptic VesiclesConceptsSynaptic vesicle exocytosisSynaptic vesicle recyclingPhotoreceptor ribbon synapseVesicle exocytosisVesicle recyclingVesicle cycleVesicle releaseRibbon synapseProtein synthesisProperties of synaptic transmissionMolecular componentsMouse rodsSynaptic terminalsRod cellsProteinVesiclesRod photoreceptorsDim lightSynaptic transmissionInner segmentsCellsExocytosisEndocytosisOuter segmentsEnergy production
2024
Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release
Bose D, Bera M, Norman C, Timofeeva Y, Volynski K, Krishnakumar S. Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release. Nature Communications 2024, 15: 10741. PMID: 39738049, PMCID: PMC11685451, DOI: 10.1038/s41467-024-54960-1.Peer-Reviewed Original ResearchConceptsSynaptotagmin-7Synaptotagmin-1Protein machinerySNARE complex assemblyFusion clampExocytosis processVesicle fusionVesicular fusionComplex assemblySynaptic vesiclesFusion assayMolecular basisPhysiologically relevant conditionsPresynaptic calcium influxNeurotransmitter releaseVesiclesSNAREProteinMachineryCompetitive bindingFusion dynamicsComplexinExocytosisFusionCalcium influxCB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum
Choi J, Acharya R, Lim H, Lee K, Seo J, Yang E, Kim H, Yoon J, Chang D, Kim S, Kim S, Birnbaumer L, Suh-Kim H. CB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2409773121. PMID: 39602265, PMCID: PMC11626142, DOI: 10.1073/pnas.2409773121.Peer-Reviewed Original ResearchConceptsDepolarization-induced suppression of excitationCannabinoid receptor type 1Synaptic plasticityDepolarization-induced suppressionSuppression of excitationHeterotrimeric Go proteinAbundant G proteinGi/o-coupled receptorsNeurotransmitter releasePresynaptic terminalsReceptor type 1Regulate neurotransmitter releaseBeam balance testBrain synaptosomal fractionsRegulating neurotransmittersMutated animalsMultiple proteinsKO miceProteomic analysisMotor deficitsCB1RCerebellumEpileptic encephalopathyGo proteinsSignaling pathwayDual-Ring SNAREpin Machinery Tuning for Fast Synaptic Vesicle Fusion
Caruel M, Pincet F. Dual-Ring SNAREpin Machinery Tuning for Fast Synaptic Vesicle Fusion. Biomolecules 2024, 14: 600. PMID: 38786007, PMCID: PMC11117985, DOI: 10.3390/biom14050600.Peer-Reviewed Original ResearchIn Vivo Synaptic Density in Early Schizophrenia: Are There No Differences or Are They Too Small to Detect?
Radhakrishnan R. In Vivo Synaptic Density in Early Schizophrenia: Are There No Differences or Are They Too Small to Detect? Biological Psychiatry 2024, 95: 605-607. PMID: 38479976, DOI: 10.1016/j.biopsych.2024.01.016.Peer-Reviewed Original ResearchConceptsSynaptic densityImpaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs
Zhu F, Shi Q, Jiang Y, Zhang Y, Zhao H. Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs. Molecular Autism 2024, 15: 9. PMID: 38297387, PMCID: PMC10829216, DOI: 10.1186/s13229-024-00587-4.Peer-Reviewed Original ResearchConceptsPrefrontal cortexPyramidal neuronsSHANK3 mutationsPrefrontal cortex neuronal activityPrefrontal cortex pyramidal neuronsSocial behaviorBrain slicesPrefrontal cortex's roleSynaptic transmissionPrefrontal cortex layersStudy social cognitionAutism spectrum disorderAutism-like behaviorsDendritic spine morphologyReduced dendritic complexitySocial cognitionSocial impairmentBehavioral alterationsNeural mechanismsExcitatory synaptic transmissionMutant rodent modelsHeightened anxietySpectrum disorderSpine densityImpaired synaptic functionSynaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling
Zhang D, Ruan J, Peng S, Li J, Hu X, Zhang Y, Zhang T, Ge Y, Zhu Z, Xiao X, Zhu Y, Li X, Li T, Zhou L, Gao Q, Zheng G, Zhao B, Li X, Zhu Y, Wu J, Li W, Zhao J, Ge W, Xu T, Jia J. Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling. Nature Neuroscience 2024, 27: 232-248. PMID: 38168932, PMCID: PMC10849963, DOI: 10.1038/s41593-023-01515-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriolesAxonsMiceMyocytes, Smooth MuscleNeurovascular CouplingSynaptic TransmissionVasodilationConceptsArteriolar smooth muscle cellsSmooth muscle cellsNeurovascular couplingPrevent Ca2+ overloadMuscle cellsNMDA receptor subunit 1Cerebral neurovascular couplingCa2+ overloadMouse cerebral cortexGluN1 subunitGlutamatergic axonsArteriolar constrictionSpreading depolarizationCerebral ischemiaCell-type specificityFunctional hyperemiaCerebral cortexPostsynaptic dendritesBrain atrophyCell junctionsArteriolesBrain functionAxonsBrainCells
2023
The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses
Norman C, Krishnakumar S, Timofeeva Y, Volynski K. The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses. Communications Biology 2023, 6: 1091. PMID: 37891212, PMCID: PMC10611806, DOI: 10.1038/s42003-023-05445-2.Peer-Reviewed Original ResearchConceptsFusion clampSV exocytosisSynaptic vesiclesNeurotransmitter releaseSNARE complexSNARE proteinsSV fusionPhysiological timescalesSynaptotagmin-1Synergistic regulationMolecular biochemistryComplete assemblyPresynaptic proteinsSynaptotagmin-7Molecular architectureCalcium bindingExocytosisDual bindingProteinCentral synapsesBindingPlasticitySynaptotagminSnareVesiclesElectrical properties of dendritic spines
Zecevic D. Electrical properties of dendritic spines. Biophysical Journal 2023, 122: 4303-4315. PMID: 37837192, PMCID: PMC10698282, DOI: 10.1016/j.bpj.2023.10.008.Peer-Reviewed Original ResearchConceptsDendritic spinesIntracellular calcium concentration changesCortical pyramidal neuronsExcitatory synaptic transmissionCalcium concentration changesBasal dendritesPyramidal neuronsMushroom spinesSpine synapsesSynaptic transmissionBrain slicesVoltage-sensitive dyeNervous systemSpine neckSignificant physiological roleSynaptic signalingTwo-photon uncagingElectrical compartmentsSpineOnly experimental studiesBiochemical compartmentalizationPhysiological roleDifferent preparationsAnatomical structuresAdequate sensitivityTurbocharging synaptic transmission
Rothman J, Grushin K, Bera M, Pincet F. Turbocharging synaptic transmission. FEBS Letters 2023, 597: 2233-2249. PMID: 37643878, DOI: 10.1002/1873-3468.14718.Peer-Reviewed Original ResearchRoles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery
Sundaram R, Chatterjee A, Bera M, Grushin K, Panda A, Li F, Coleman J, Lee S, Ramakrishnan S, Ernst A, Gupta K, Rothman J, Krishnakumar S. Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2309516120. PMID: 37590407, PMCID: PMC10450444, DOI: 10.1073/pnas.2309516120.Peer-Reviewed Original ResearchMeSH KeywordsBlisterDiglyceridesExocytosisHumansSynaptic TransmissionSynaptic VesiclesSynaptotagminsConceptsCore protein machineryRelease-ready vesiclesSynaptic vesicle primingVesicle primingProtein machinerySingle-molecule imagingSNAREpin assemblyFunctional intermediatesFunctional reconstitutionMunc13DiacylglycerolCoordinated actionMunc18VesiclesMachineryComplete reconstitutionNew roleSelective effectDetailed characterizationChaperonesRate of caReconstitutionVAMP2ComplexinMutationsChemogenetic regulation of the TARP-lipid interaction mimics LTP and reversibly modifies behavior
Park J, Berthoux C, Hoyos-Ramirez E, Shan L, Morimoto-Tomita M, Wang Y, Castillo P, Tomita S. Chemogenetic regulation of the TARP-lipid interaction mimics LTP and reversibly modifies behavior. Cell Reports 2023, 42: 112826. PMID: 37471228, PMCID: PMC10528344, DOI: 10.1016/j.celrep.2023.112826.Peer-Reviewed Original ResearchGlia-neuron coupling via a bipartite sialylation pathway promotes neural transmission and stress tolerance in Drosophila
Scott H, Novikov B, Ugur B, Allen B, Mertsalov I, Monagas-Valentin P, Koff M, Robinson S, Aoki K, Veizaj R, Lefeber D, Tiemeyer M, Bellen H, Panin V. Glia-neuron coupling via a bipartite sialylation pathway promotes neural transmission and stress tolerance in Drosophila. ELife 2023, 12: e78280. PMID: 36946697, PMCID: PMC10110239, DOI: 10.7554/elife.78280.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrosophilaNervous System Physiological PhenomenaNeurogliaNeuronsPolysaccharidesSynaptic TransmissionConceptsSialylation pathwayCMP-sialic acid synthetaseStress toleranceAnimal developmentProtein functionVoltage-gated sodium channelsGlycan terminiNeural transmissionDedicated pathwaysGenesDifferent cellsPathwayOxidative stressSodium channelsSialic acidNervous systemNeural excitabilitySialylationToleranceNormal levelsNeural functionDrosophilaTerminusExcitabilitySynthetaseRibbon Synapses and Retinal Disease: Review
Frederick C, Zenisek D. Ribbon Synapses and Retinal Disease: Review. International Journal Of Molecular Sciences 2023, 24: 5090. PMID: 36982165, PMCID: PMC10049380, DOI: 10.3390/ijms24065090.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPresynaptic protein complexesRibbon synapsesDefective synaptic transmissionMolecular machineryProtein complexesRetinal malfunctionSynaptic transmissionRetinal diseasesSynaptic ribbonsNeurotransmitter releaseMuscular dystrophyVisual diseaseSynapsesDiseaseSensory informationMutagenesisMachineryPresent understandingSynaptopathyVisual systemReviewPathogenesisRetinaPathologyNonquantal transmission at the vestibular hair cell–calyx synapse: KLV currents modulate fast electrical and slow K+ potentials
Govindaraju A, Quraishi I, Lysakowski A, Eatock R, Raphael R. Nonquantal transmission at the vestibular hair cell–calyx synapse: KLV currents modulate fast electrical and slow K+ potentials. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2207466120. PMID: 36595693, PMCID: PMC9926171, DOI: 10.1073/pnas.2207466120.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsHair Cells, VestibularPotassium ChlorideSynapsesSynaptic TransmissionVestibule, LabyrinthConceptsNonquantal transmissionAfferent neuronsHair cellsPresynaptic hair cellsPrimary afferent neuronsAction potential latencyVestibular hair cellsCalyx afferentsPotential latencySynaptic terminalsVestibular signalsSynaptic cleftNeural circuitsHead positionPossible roleGap junctionsNeuronsSynapsesSynapseCleftCellsCalyxAfferents
2022
Local connectivity and synaptic dynamics in mouse and human neocortex
Campagnola L, Seeman SC, Chartrand T, Kim L, Hoggarth A, Gamlin C, Ito S, Trinh J, Davoudian P, Radaelli C, Kim MH, Hage T, Braun T, Alfiler L, Andrade J, Bohn P, Dalley R, Henry A, Kebede S, Alice M, Sandman D, Williams G, Larsen R, Teeter C, Daigle TL, Berry K, Dotson N, Enstrom R, Gorham M, Hupp M, Dingman Lee S, Ngo K, Nicovich PR, Potekhina L, Ransford S, Gary A, Goldy J, McMillen D, Pham T, Tieu M, Siverts L, Walker M, Farrell C, Schroedter M, Slaughterbeck C, Cobb C, Ellenbogen R, Gwinn RP, Keene CD, Ko AL, Ojemann JG, Silbergeld DL, Carey D, Casper T, Crichton K, Clark M, Dee N, Ellingwood L, Gloe J, Kroll M, Sulc J, Tung H, Wadhwani K, Brouner K, Egdorf T, Maxwell M, McGraw M, Pom CA, Ruiz A, Bomben J, Feng D, Hejazinia N, Shi S, Szafer A, Wakeman W, Phillips J, Bernard A, Esposito L, D'Orazi FD, Sunkin S, Smith K, Tasic B, Arkhipov A, Sorensen S, Lein E, Koch C, Murphy G, Zeng H, Jarsky T. Local connectivity and synaptic dynamics in mouse and human neocortex. Science 2022, 375: eabj5861. PMID: 35271334, PMCID: PMC9970277, DOI: 10.1126/science.abj5861.Peer-Reviewed Original ResearchControl of Synapse Structure and Function by Actin and Its Regulators
Gentile JE, Carrizales MG, Koleske AJ. Control of Synapse Structure and Function by Actin and Its Regulators. Cells 2022, 11: 603. PMID: 35203254, PMCID: PMC8869895, DOI: 10.3390/cells11040603.Peer-Reviewed Original ResearchConceptsActin poolsOrganization of proteinsSynaptic actinOrganization of actinDisease risk genesKey neuronal functionsPost-synaptic compartmentsActin regulatorsDynamic regulationActin filamentsWhole-exome sequencingRisk genesIon channelsGenetic variantsActinRegulatorNeuronal functionSynapse structureExome sequencingPostsynaptic dendritic spinesKey functionsSpecialized junctionsGenesPresynaptic axon terminalsAxon terminals
2021
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo
Shao LX, Liao C, Gregg I, Davoudian PA, Savalia NK, Delagarza K, Kwan AC. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron 2021, 109: 2535-2544.e4. PMID: 34228959, PMCID: PMC8376772, DOI: 10.1016/j.neuron.2021.06.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexDendritesDendritic SpinesFemaleFrontal LobeMaleMiceNeuronal PlasticityPsilocybinPyramidal CellsSynaptic TransmissionConceptsFrontal cortexDendritic spinesMouse medial frontal cortexLayer 5 pyramidal neuronsSpine formation ratesApical dendritic spinesMedial frontal cortexUntapped therapeutic potentialPyramidal neuronsSingle doseExcitatory neurotransmissionBehavioral deficitsBeneficial actionsStructural remodelingSynaptic rewiringMammalian brainTherapeutic potentialNeural adaptationUse of psychedelicsSerotonergic psychedelicsSpine sizeTwo-photon microscopyCortexPsilocybinSpine
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