2024
Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons
Wu J, Quraishi I, Zhang Y, Bromwich M, Kaczmarek L. Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons. Cell Reports 2024, 43: 113904. PMID: 38457342, PMCID: PMC11013952, DOI: 10.1016/j.celrep.2024.113904.Peer-Reviewed Original ResearchInhibitory neuronsRegulation of neuronal excitabilityPotassium channel mutationsVoltage-dependent sodiumInhibitory cortical neuronsGain-of-function mutationsAxon initial segmentKCNT1 geneNeuronal excitabilityChannel subunitsChannel mutationsNetwork hyperexcitabilityMouse modelNeuron typesCortical neuronsTreat epilepsyNeuronsExcitable neuronsNeurological disordersSevere intellectual disabilityMutationsInitial segmentKCNT1ExpressionHyperexcitabilityThe 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 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 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 gene
2023
Forming new connections: Advances in human stem-cell-derived interneuron therapy for treating epilepsy
Gupta J, Naegele J. Forming new connections: Advances in human stem-cell-derived interneuron therapy for treating epilepsy. Neuron 2023, 111: 758-760. PMID: 36924760, DOI: 10.1016/j.neuron.2023.02.034.Peer-Reviewed Original Research
2020
Mechanisms underlying auditory processing deficits in Fragile X syndrome
McCullagh EA, Rotschafer SE, Auerbach BD, Klug A, Kaczmarek LK, Cramer KS, Kulesza RJ, Razak KA, Lovelace JW, Lu Y, Koch U, Wang Y. Mechanisms underlying auditory processing deficits in Fragile X syndrome. The FASEB Journal 2020, 34: 3501-3518. PMID: 32039504, PMCID: PMC7347277, DOI: 10.1096/fj.201902435r.Peer-Reviewed Original ResearchConceptsAuditory dysfunctionAutism spectrum disorderAuditory brainstem circuitsFragile X syndromeAuditory processing deficitsCommon monogenetic causeNetwork hyperexcitabilityBrainstem circuitsAuditory pathwayAuditory cortexNeuronal plasticityAnimal modelsAuditory hypersensitivitySynaptic developmentHyperacusisMonogenetic causeDysfunctionX syndromeAberrant synaptic developmentBody of dataUnderlying mechanismMultiple mechanismsHuman therapySyndromeProcessing deficits
2017
Inhibitory or excitatory? Optogenetic interrogation of the functional roles of GABAergic interneurons in epileptogenesis
Ye H, Kaszuba S. Inhibitory or excitatory? Optogenetic interrogation of the functional roles of GABAergic interneurons in epileptogenesis. Journal Of Biomedical Science 2017, 24: 93. PMID: 29202749, PMCID: PMC5715558, DOI: 10.1186/s12929-017-0399-8.Peer-Reviewed Original ResearchConceptsGABAergic interneuronsEpileptic circuitrySeizure suppressionGABA depletionSeizure controlExcitatory effectsGABAergic cellsGABAergic inhibitionNetwork hyperexcitabilityPyramidal neuronsNeuronal balancePyramidal cellsEpileptic circuitsInhibitory neuronsPostsynaptic neuronsGABA receptorsPostsynaptic cellInterneuronsOptogenetic excitationOptogenetic protocolsCircuitry levelEpileptogenesisOptogenetic interrogationInhibitory effectContext-dependent role
2012
Seizures as imbalanced up states: excitatory and inhibitory conductances during seizure-like events
Žiburkus J, Cressman J, Schiff S. Seizures as imbalanced up states: excitatory and inhibitory conductances during seizure-like events. Journal Of Neurophysiology 2012, 109: 1296-1306. PMID: 23221405, PMCID: PMC3602838, DOI: 10.1152/jn.00232.2012.Peer-Reviewed Original ResearchConceptsSeizure-like eventsO-LM cellsPyramidal cellsInhibitory conductanceOriens-lacunosum moleculare (O-LM) interneuronsNeuronal network hyperexcitabilityExcitability of interneuronsCA1 pyramidal cellsInhibitory synaptic conductancesNetwork hyperexcitabilityRecurrent seizuresMoleculare interneuronsSeizure initiationNeural network activityRat hippocampusExtracellular magnesiumSynaptic barragesFiring patternsSeizuresExcitatoryCellular subtypesSynaptic conductancesInterneuronsNetwork activityCell types
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