2025
Molecular 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 ResearchConceptsSynaptic vesicle exocytosisSynaptic vesicle recyclingPhotoreceptor ribbon synapseVesicle exocytosisVesicle recyclingVesicle cycleVesicle releaseRibbon synapseProtein synthesisProperties of synaptic transmissionMolecular componentsMouse rodsSynaptic terminalsRod cellsProteinVesiclesRod photoreceptorsDim lightSynaptic transmissionInner segmentsCellsExocytosisEndocytosisOuter segmentsEnergy productionSynaptic Function
Kullmann D, Volynski K. Synaptic Function. 2025, 265-296. DOI: 10.1093/med/9780190065324.003.0006.Peer-Reviewed Original Research
2024
Development of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain
Fernandes E, Palner M, Raval N, Jeppesen T, Danková D, Bærentzen S, Werner C, Eilts J, Maric H, Doose S, Aripaka S, Kaalund S, Aznar S, Kjaer A, Schlosser A, Haugaard-Kedström L, Knudsen G, Herth M, Stro̷mgaard K. Development of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain. Journal Of Medicinal Chemistry 2024, 67: 11975-11988. PMID: 38981131, DOI: 10.1021/acs.jmedchem.4c00615.Peer-Reviewed Original ResearchPostsynaptic densityBrain slicesPSD-95Tracer bindingPostsynaptic density protein 95Rat brain slicesMolecular imagingPost-mortem Parkinson's diseaseScaffold proteinQuantitative autoradiographyAbundant proteinsSynaptic transmissionPostsynaptic impairmentHigh-affinity inhibitorsSignaling moleculesImaging studiesFluorescent tagsCell imaging studiesMonozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission
Stern S, Zhang L, Wang M, Wright R, Rosh I, Hussein Y, Stern T, Choudhary A, Tripathi U, Reed P, Sadis H, Nayak R, Shemen A, Agarwal K, Cordeiro D, Peles D, Hang Y, Mendes A, Baul T, Roth J, Coorapati S, Boks M, McCombie W, Hulshoff Pol H, Brennand K, Réthelyi J, Kahn R, Marchetto M, Gage F. Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission. Molecular Psychiatry 2024, 29: 3208-3222. PMID: 38704507, PMCID: PMC11449799, DOI: 10.1038/s41380-024-02561-1.Peer-Reviewed Original ResearchCo-twinSchizophrenia patientsMonozygotic twinsHippocampal synaptic deficitsHealthy twinsSynapse-related genesDepressive disorderPsychiatric disordersSchizophreniaControl twinsTwin pairsSynaptic activitySynaptic deficitsTwin siblingsNeurophysiological abnormalitiesGroup of patientsSynaptic transmissionDiscordant twinsDisordersHippocampal neuronsNeuronsReprogrammed iPSCsIPSC modelsPatientsSiblingsPresynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment
Wang J, Huang Q, He K, Li J, Guo T, Yang Y, Lin Z, Li S, Vanderlinden G, Huang Y, Van Laere K, Guan Y, Guo Q, Ni R, Li B, Xie F. Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment. Alzheimer's & Dementia 2024, 20: 3876-3888. PMID: 38634334, PMCID: PMC11180932, DOI: 10.1002/alz.13817.Peer-Reviewed Original ResearchMGluR5 availabilityMedial temporal lobeSynaptic densityTemporal lobeHealthy controlsAlzheimer's diseaseMetabotropic glutamate receptor 5Glutamate receptor 5Synaptic lossIntegrative brain functionsCognitively impaired patientsEarly cognitive impairmentGlobal cognitionMGluR5 signalingMediation analysisPathophysiological mechanism of Alzheimer's diseaseBrain functionCognitive impairmentMGluR5CognitionImproving synaptic functionImpaired patientsSynaptic functionSynaptic transmissionAmyloid pathologyTomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes
Meijer M, Öttl M, Yang J, Subkhangulova A, Kumar A, Feng Z, van Voorst T, Groffen A, van Weering J, Zhang Y, Verhage M. Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes. Nature Communications 2024, 15: 2652. PMID: 38531902, PMCID: PMC10965968, DOI: 10.1038/s41467-024-46828-1.Peer-Reviewed Original ResearchConceptsSynaptobrevin-2/VAMP2SNARE assemblySNARE motifC-terminal polybasic regionSNAP-25 bindingSNARE complex assemblyTemplate complexStructure-function analysisMunc18-1Syntaxin-1Polybasic regionTomosynSNAP-25Membrane fusionSynaptic vesiclesSingle-molecule force measurementsEssential intermediateSNAREMotifInhibitory functionAssemblyMouse modelMunc18Synaptic transmissionSynaptic strengthMicroglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids
Wu J, Zhang J, Chen X, Wettschurack K, Que Z, Deming B, Olivero-Acosta M, Cui N, Eaton M, Zhao Y, Li S, Suzuki M, Chen I, Xiao T, Halurkar M, Mandal P, Yuan C, Xu R, Koss W, Du D, Chen F, Wu L, Yang Y. Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids. Molecular Psychiatry 2024, 29: 2424-2437. PMID: 38499656, DOI: 10.1038/s41380-024-02518-4.Peer-Reviewed Original ResearchAutism spectrum disorderSpine densityAssociated with autism spectrum disorderLower spine densitySynaptic transmissionHuman cellsPost-synapseProtein-truncating mutationsNeurodevelopmental disorder affecting 1Phagocytosis of synapsesNeuro-immune responsesImpaired learningIntellectual disabilityNeuro-immune interactionsHuman genetic studiesRestoring synaptic transmissionReduced synaptic transmissionAblation of microgliaSpectrum disorderResident immune cellsHuman cerebral organoid modelCerebral organoidsBrain developmentCerebral organoid modelSCN2A mutationsThe mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function
Nguyen L, Xu Y, Nair M, Bordey A. The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function. ELife 2024, 12 DOI: 10.7554/elife.91010.3.Peer-Reviewed Original ResearchMouse medial prefrontal cortexMedial prefrontal cortexFocal malformations of cortical developmentMalformations of cortical developmentExcitatory synaptic activityExcitatory synaptic transmissionCortical neuron developmentPyramidal neuron morphologyMechanisms of hyperexcitabilityResponse to therapeutic interventionsMTORC1 signalingGene-specific mechanismsPrefrontal cortexFocal malformationsBrain somatic mutationsMTOR complex 1Membrane excitabilityBiallelic inactivationClinical manifestationsGene mutationsNetwork hyperexcitabilitySynaptic transmissionSynaptic activityIntractable epilepsyRepressor geneThe mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function
Nguyen L, Xu Y, Nair M, Bordey A. The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function. ELife 2024, 12: rp91010. PMID: 38411613, PMCID: PMC10942629, DOI: 10.7554/elife.91010.Peer-Reviewed Original ResearchConceptsMouse medial prefrontal cortexMedial prefrontal cortexFocal malformations of cortical developmentMalformations of cortical developmentExcitatory synaptic activityExcitatory synaptic transmissionCortical neuron developmentPyramidal neuron morphologyMechanisms of hyperexcitabilityResponse to therapeutic interventionsMTORC1 signalingGene-specific mechanismsPrefrontal cortexFocal malformationsBrain somatic mutationsMTOR complex 1Membrane excitabilityBiallelic inactivationClinical manifestationsGene mutationsNetwork hyperexcitabilitySynaptic transmissionSynaptic activityIntractable epilepsyRepressor geneImpaired 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 function
2023
Age‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model
Nelson R, Rangaraju S, Rayaprolu S, Kumar P, Espinosa‐Garcia C, Xiao H. Age‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.083101.Peer-Reviewed Original ResearchPV+ neuronsWild typePerineuronal netsAlzheimer's diseaseAD-like pathologyCo-localizationMouse modelAmyloid-betaFast-spiking interneuronsEarly amyloidosisRegulate synaptic transmissionSynaptic maintenanceExtracellular matrix structurePlaque proximityAge-dependent mannerMonths of agePhysiological roleImmunofluorescence microscopyNeuronal roleNeurodegenerative diseasesParvalbumin-positiveParvalbumin interneuronsAge-dependent changesSynaptic transmissionProximal dendritesIncreased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia
Benson C, King J, Kauer S, Waxman S, Tan A. Increased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia. Journal Of Neurophysiology 2023, 130: 1358-1366. PMID: 37877184, PMCID: PMC10972632, DOI: 10.1152/jn.00234.2023.Peer-Reviewed Original ResearchConceptsSpinal cord injuryRate-dependent depressionTripartite synapsesGLT-1Astrocytic GLT-1 expressionChronic neurological complicationsGLT-1 expressionAstrocyte involvementChronic spasticityUninjured shamsNeurological complicationsNeuropathic painHyperexcitability disordersH-reflexPSD-95 proteinReactive astrocytesVentral hornCord injuryMuscle toneAstrocytes' roleSpinal cordSpinal circuitsSynaptic transmissionHyperreflexiaSpasticityElectrical 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 ResearchChemogenetic 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 ResearchCochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
Liu H, Liu H, Wang L, Song L, Jiang G, Lu Q, Yang T, Peng H, Cai R, Zhao X, Zhao T, Wu H. Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform. Nature Communications 2023, 14: 3085. PMID: 37248244, PMCID: PMC10227054, DOI: 10.1038/s41467-023-38621-3.Peer-Reviewed Original ResearchConceptsShort isoformEndocytic membrane retrievalRNA sequencing techniquesDiverse biological functionsInner hair cellsTranscript diversityUnannotated transcriptsRNA-seqAlternative isoformsMembrane retrievalBiological functionsGENCODE databasesKey proteinsIsoform resolutionSequencing techniquesSustained exocytosisIsoformsMechanistic understandingAuditory functionSanger sequencingHair cellsTranscriptsRT-PCRSynaptic transmissionAuditory phenotypeGlutamatergic Pathways and Receptors
Tomita S. Glutamatergic Pathways and Receptors. 2023, 197-200. DOI: 10.1007/978-3-031-15070-8_30.Peer-Reviewed Original ResearchGlutamate receptorsSynaptic transmissionSynaptic plasticityReceptor activityGlutamate receptor activityGlutamate-gated cation channelsMajor excitatory neurotransmitterGi/oG protein-coupled receptorsProtein-coupled receptorsGlutamate releaseExcitatory neurotransmitterNMDA receptorsGlutamatergic pathwaysKainate receptorsAMPA receptorsTherapeutic strategiesDistinct synapsesPostsynaptic signalingNeurological disordersSynaptic strengthGq signalingNeurodegenerative diseasesReceptorsCation channelsRibbon 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 systemReviewPathogenesisRetinaPathology
2022
Dendritic Spines and Pain Memory
Benson C, King J, Reimer M, Kauer S, Waxman S, Tan A. Dendritic Spines and Pain Memory. The Neuroscientist 2022, 30: 294-314. PMID: 36461773, DOI: 10.1177/10738584221138251.Peer-Reviewed Original ResearchNeuropathic painDendritic spinesSynaptic transmissionSpinal cord dorsal hornForm of painNew therapeutic approachesSurface of neuronsDorsal hornIntractable painDeep laminaePain memoryTherapeutic approachesPainNervous systemNew therapeuticsSpineMillions of peopleInjuryDiseaseRecent studiesReview articlePrevalenceNeuronsImportant roleBiodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1
Rischka L, Murgaš M, Pichler V, Vraka C, Rausch I, Winkler D, Nics L, Rasul S, Silberbauer LR, Reed MB, Godbersen GM, Unterholzner J, Handschuh P, Gryglewski G, Mindt T, Mitterhauser M, Hahn A, Ametamey SM, Wadsak W, Lanzenberger R, Hacker M. Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1. EJNMMI Research 2022, 12: 53. PMID: 36018389, PMCID: PMC9418393, DOI: 10.1186/s13550-022-00925-8.Peer-Reviewed Original ResearchExtrasynaptic NMDA receptorsStandardized uptake valueNMDA receptorsUrinary bladderEffective dose coefficientsPET radioligandNeuropsychiatric disordersTreatment monitoringSynaptic NMDA receptorsTime-integrated activity coefficientsCentral nervous systemUrinary bladder contentsDrug developmentDose coefficientsAdverse eventsExcitotoxic processTRIAL REGISTRATIONBladder contentsHealthy subjectsSynaptic transmissionSide effectsBone marrowNervous systemUptake valueEffective dose
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