2025
Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice
Lin J, Callender J, Mayfield J, McClatchy D, Ojeda-Juárez D, Pourhamzeh M, Soldau K, Kurt T, Danque G, Khuu H, Ronson J, Pizzo D, Du Y, Gruber M, Sevillano A, Wang J, Orrú C, Chen J, Funk G, Aguilar-Calvo P, Aulston B, Roy S, Rho J, Bui J, Newton A, Lipton S, Caughey B, Patrick G, Doré K, Yates J, Sigurdson C. Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice. Journal Of Clinical Investigation 2025, 135: e186432. PMID: 40185484, PMCID: PMC12077891, DOI: 10.1172/jci186432.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsProtein kinase CAmino terminusPrion proteinN-methyl-D-aspartateMutant prion proteinNMDA receptor activationN-linked glycosylation sitesExcitatory-inhibitory imbalanceHippocampal pyramidal neuronsDownstream signaling eventsActivate protein kinase CNMDAR channelsNeuronal hyperexcitabilityFunctional motifsGlutamate receptorsCalcium influxPhosphoproteomic analysisPyramidal neuronsGlycosylation sitesSignaling eventsReceptor activationPrion-infected miceDendritic beadingSynapse lossPsilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors
Shao L, Liao C, Davoudian P, Savalia N, Jiang Q, Wojtasiewicz C, Tan D, Nothnagel J, Liu R, Woodburn S, Bilash O, Kim H, Che A, Kwan A. Psilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors. Nature 2025, 642: 411-420. PMID: 40175553, PMCID: PMC12188471, DOI: 10.1038/s41586-025-08813-6.Peer-Reviewed Original ResearchConceptsMedial frontal cortexFrontal cortexMouse medial frontal cortexSingle dose of psilocybinDose of psilocybinImpact of psilocybinDensity of dendritic spinesPyramidal cell typesStress-related behaviorsDendritic spinesStress-related phenotypesCell-type-specific electrophysiologyPsilocybin effectsPT neuronsSerotonergic psychedelicsRemodeling of dendritic spinesCell typesElevated firing ratesPyramidal tractPsilocybinIT neuronsPsychedelicsStructural plasticityFiring rateCalcium transientsTranslaminar synchronous neuronal activity is required for columnar synaptic strengthening in the mouse neocortex
Vargas-Ortiz J, Lin L, Martinez V, Liu R, Babij R, Duan Z, Wacks S, Sun L, Wang A, Khan S, Soto-Vargas J, De Marco García N, Che A. Translaminar synchronous neuronal activity is required for columnar synaptic strengthening in the mouse neocortex. Nature Communications 2025, 16: 1296. PMID: 39900899, PMCID: PMC11791040, DOI: 10.1038/s41467-024-55783-w.Peer-Reviewed Original ResearchThis study shows how connections across layers in the cortex synchronize early brain activity, guiding sensory development and informing strategies to address neurodevelopmental disorders.Chronic Rapamycin Prevents Electrophysiological and Morphological Alterations Produced by Conditional Pten Deletion in Mouse Cortex
Hauptman J, Antonios J, Mathern G, Levine M, Cepeda C. Chronic Rapamycin Prevents Electrophysiological and Morphological Alterations Produced by Conditional Pten Deletion in Mouse Cortex. Cells 2025, 14: 79. PMID: 39851507, PMCID: PMC11764219, DOI: 10.3390/cells14020079.Peer-Reviewed Original ResearchConceptsCortical pyramidal neuronsMice treated with rapamycinGABA releasePTEN deletionWhole-cell patch-clamp recordingsMiniature inhibitory postsynaptic currentsEx vivo slicesNeuronal somatic sizeReduced neuronal firingInhibitory postsynaptic currentsChronic rapamycin treatmentPatch-clamp recordingsIncreased input resistanceInhibitory synaptic inputsDevelopmental brain disordersRapamycin treatmentIncreased membrane capacitanceConditional mouse modelChronic treatmentPostsynaptic currentsClamp recordingsNaive miceSynaptic excitationBrain disordersControl mice
2024
Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarityThe 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 ResearchMeSH KeywordsAnimalsBrainDrug Resistant EpilepsyMechanistic Target of Rapamycin Complex 1MiceNeuronsPyramidal CellsConceptsMouse 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
Electrical 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 sensitivityVIP interneurons regulate cortical size tuning and visual perception
Ferguson K, Salameh J, Alba C, Selwyn H, Barnes C, Lohani S, Cardin J. VIP interneurons regulate cortical size tuning and visual perception. Cell Reports 2023, 42: 113088. PMID: 37682710, PMCID: PMC10618959, DOI: 10.1016/j.celrep.2023.113088.Peer-Reviewed Original ResearchConceptsState-dependent modulationPyramidal neuronsVIP-INsBehavioral state-dependent modulationCortical circuit functionVasoactive intestinal peptidePrimary visual cortexAwake behaving miceIntestinal peptideGABAergic interneuronsVIP interneuronsCortical activityVisual cortexBehaving miceFeature selectivityInterneuronsSensory processingSpecialized populationCircuit functionStimulus sizeActivity altersDiverse populationsModulationPopulationCortexIn Utero Electroporated Neurons for Medium-Throughput Screening of Compounds Regulating Neuron Morphology
Sokolov A, Aurich M, Bordey A. In Utero Electroporated Neurons for Medium-Throughput Screening of Compounds Regulating Neuron Morphology. ENeuro 2023, 10: eneuro.0160-23.2023. PMID: 37620147, PMCID: PMC10464655, DOI: 10.1523/eneuro.0160-23.2023.Peer-Reviewed Original ResearchConceptsSomatosensory cortexCortical pyramidal neuronsTreatment of epilepsyNeurite overgrowthNeurologic disabilityPyramidal neuronsSoma sizeNovel agentsCircuit alterationsSide effectsMorphologic assessmentMouse neuronsRelated disordersDiseased neuronsMTOR activatorDrug efficacyCandidate therapeuticsNeuronsNeuron morphologyMTOR activityMedium-throughput screeningNeurodevelopmental disordersNeurite lengthMorphologic measurementsDisordersDevelopmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics
Batista-Brito R, Majumdar A, Nuño A, Ward C, Barnes C, Nikouei K, Vinck M, Cardin J. Developmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics. Molecular Psychiatry 2023, 28: 3133-3143. PMID: 37069344, PMCID: PMC10618960, DOI: 10.1038/s41380-023-02066-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsInterneuronsMiceNeuregulin-1NeuronsParvalbuminsPyramidal CellsReceptor, ErbB-4Signal TransductionConceptsPV interneuronsCortical neuronsCortical circuitsCortical circuit dynamicsCortical GABAergic cellsNRG1/ErbB4Excitatory cortical neuronsParvalbumin-Expressing InterneuronsInhibitory cortical neuronsApical dendritic tuftsActivity of excitatorySecond postnatal weekProper synaptic connectivityLate postnatal developmentState-dependent modulationLoss of ERBB4Excitatory componentGABAergic cellsGABAergic inhibitionSpine densityDendritic tuftsPostnatal weekNormal tuningSynaptic connectivityReceptor ErbB4
2022
Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex
Babij R, Ferrer C, Donatelle A, Wacks S, Buch A, Niemeyer J, Ma H, Duan Z, Fetcho R, Che A, Otsuka T, Schwartz T, Huang B, Liston C, De Marco García N. Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex. Neuron 2022, 111: 256-274.e10. PMID: 36446382, PMCID: PMC9852093, DOI: 10.1016/j.neuron.2022.10.037.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderHumansMicePyramidal CellsReceptors, GABA-ASomatosensory CortexSynapsesTouchConceptsAssociated with autism spectrum disorderNeuronal subtypesAngelman syndromePyramidal neuron subtypesAssociated with neurodevelopmental disordersGABAergic synapsesWidefield calcium imagingPyramidal neuronsAutism spectrum disorderNeonatal stageTwo-photonCalcium imagingResponse to tactile stimulationGABRB3Developmental decreaseSomatosensory cortexAtypical connectivityNetwork synchronyFunctional connectivitySpectrum disorderInterhemispheric circuitInhibitory functionSensory processingNeurodevelopmental disordersASD subjects
2021
An in vivo Calcium Imaging Approach for the Identification of Cell-Type Specific Patterns in the Developing Cortex
Che A, De Marco García N. An in vivo Calcium Imaging Approach for the Identification of Cell-Type Specific Patterns in the Developing Cortex. Frontiers In Neural Circuits 2021, 15: 747724. PMID: 34690708, PMCID: PMC8528153, DOI: 10.3389/fncir.2021.747724.Peer-Reviewed Original ResearchConceptsNeuronal activityUn-anesthetized miceCalcium imaging approachesGenetically encoded calcium sensorsCranial window surgeryCohort of neuronsMouse somatosensory cortexSST interneuronsVIP interneuronsPostnatal dayCell-type specific patternsPyramidal cellsInterneuron populationsNeuronal cohortsNeuronal diversityInterneuronsDeveloping cortexPostnatal stagesNeuronal populationsSomatosensory cortexNeuronsMiceCohortCortexNetwork activityPsilocybin 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 ResearchConceptsFrontal 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 microscopyCortexPsilocybinSpineSelective Overexpression of Collybistin in Mouse Hippocampal Pyramidal Cells Enhances GABAergic Neurotransmission and Protects against PTZ-Induced Seizures
George S, James S, De Blas A. Selective Overexpression of Collybistin in Mouse Hippocampal Pyramidal Cells Enhances GABAergic Neurotransmission and Protects against PTZ-Induced Seizures. ENeuro 2021, 8: eneuro.0561-20.2021. PMID: 34083383, PMCID: PMC8281261, DOI: 10.1523/eneuro.0561-20.2021.Peer-Reviewed Original ResearchConceptsHippocampal pyramidal cellsPyramidal cellsPyramidal neuronsAdeno-associated virusGABAergic synaptic transmissionCortical pyramidal neuronsHippocampal pyramidal neuronsMouse hippocampal pyramidal cellsCultured hippocampal neuronsAbsence of gephyrinCre-dependent mannerGABAergic neurotransmissionCre miceInhibitory neurotransmissionHippocampal interneuronsInhibitory postsynapsesInhibitory synapsesHippocampal neuronsSynaptic transmissionTarget neuronsPostsynaptic sitesBrain regionsMice resultsSelective overexpressionGlycinergic postsynapsesThis is Your Brain in Meltdown
Arnsten A, Mazure CM, Sinha R. This is Your Brain in Meltdown. Scientific American 2021, 306: 48-53. PMID: 22486116, PMCID: PMC4774859, DOI: 10.1038/scientificamerican0412-48.Peer-Reviewed Original ResearchRab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex
Zhang L, Zhang X, Hsieh LS, Lin TV, Bordey A. Rab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex. Cells 2021, 10: 622. PMID: 33799820, PMCID: PMC8000154, DOI: 10.3390/cells10030622.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedDendritic SpinesExcitatory Postsynaptic PotentialsExtracellular VesiclesFemaleGene Expression Regulation, DevelopmentalGestational AgeMiceParacrine CommunicationPregnancyPyramidal Cellsrab27 GTP-Binding ProteinsSensory Receptor CellsSomatosensory CortexSynaptic TransmissionVibrissaeConceptsSmall extracellular vesiclesL4 neuronsParacrine communicationExcitatory synaptic transmissionRelease of sEVsDendritic spine formationCell-autonomous effectsRisk of autismL2/3 neuronsPyramidal neuronsLayer 2/3Somatosensory cortexBarrel cortexCortical neuronsSynaptic transmissionWhisker stimulationSomatosensory informationJuvenile miceSynaptic connectivitySynaptic integrationSpine formationBrain developmentNeuronsSensory stimulationSpine development
2020
Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex
Glausier J, Datta D, Fish K, Chung D, Melchitzky D, Lewis D. Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex. Neuroscience 2020, 452: 181-191. PMID: 33212224, PMCID: PMC7770119, DOI: 10.1016/j.neuroscience.2020.10.022.Peer-Reviewed Original ResearchConceptsCortical pyramidal neuronsDorsolateral prefrontal cortexHuman dorsolateral prefrontal cortexPyramidal neuronsDendritic spinesDensity of spinesMonkey dorsolateral prefrontal cortexPrefrontal cortexPrimate dorsolateral prefrontal cortexDeep cortical layersPyramidal neuron activitySpecific neural circuitsGABAergic inputsGlutamatergic inputsGABAergic interneuronsGlutamatergic synapsesLaminar differencesCore cognitive functionNeuron activitySynaptic informationNeuron synapseCortical layersInterneuronsRecurrent excitationCognitive functionNMDAR-Dependent Emergence of Behavioral Representation in Primary Visual Cortex
Puścian A, Benisty H, Higley MJ. NMDAR-Dependent Emergence of Behavioral Representation in Primary Visual Cortex. Cell Reports 2020, 32: 107970. PMID: 32726633, PMCID: PMC7431963, DOI: 10.1016/j.celrep.2020.107970.Peer-Reviewed Original ResearchConceptsPrimary visual cortexVisual cortexNMDA-type glutamate receptorsNeocortical sensory areasFunctional plasticityConsiderable functional plasticityPyramidal cellsGlutamate receptorsCell-autonomous expressionV1 neuronsVisual task performanceSensory areasExperience-dependent emergenceCortical networksBehavioral outputCortexVisual inputBehavioral demandsMiceNeuronsReceptorsSeizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3
Pigoni M, Hsia H, Hartmann J, Rudan Njavro J, Shmueli MD, Müller SA, Güner G, Tüshaus J, Kuhn P, Kumar R, Gao P, Tran ML, Ramazanov B, Blank B, Hipgrave Ederveen A, Von Blume J, Mulle C, Gunnersen JM, Wuhrer M, Rammes G, Busche MA, Koeglsperger T, Lichtenthaler SF. Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3. The EMBO Journal 2020, 39: embj2019103457. PMID: 32567721, PMCID: PMC7396870, DOI: 10.15252/embj.2019103457.Peer-Reviewed Original ResearchConceptsPrimary neuronsCell surface localizationMolecular functionsKainate receptor subunit GluK2Trafficking factorsSecretory pathwayNovel functionHeterologous cellsMajor substrateSurface localizationProtein 6Alzheimer's diseaseCA1 pyramidal neuronsAcute hippocampal slicesProtease BACE1Kainate-evoked currentsGlycosylationGluK2/3Pyramidal neuronsGluK2Hippocampal slicesKainate receptorsPsychiatric disordersNervous systemPsychiatric diseases
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