2024
Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI
Tiwari P, Davoudian P, Kapri D, Vuruputuri R, Karaba L, Sharma M, Zanni G, Balakrishnan A, Chaudhari P, Pradhan A, Suryavanshi S, Bath K, Ansorge M, Fernandez-Ruiz A, Kwan A, Vaidya V. Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI. Neuron 2024, 112: 3697-3714.e6. PMID: 39321791, PMCID: PMC11581910, DOI: 10.1016/j.neuron.2024.08.016.Peer-Reviewed Original ResearchAnxiolytic actionVentral hippocampusParvalbumin (PV)-positive interneuronsAnxiety-like behaviorAction of DOIPV-positive interneuronsPsychedelic DOIAnxiolytic responseAnxiolytic effectsSerotonergic psychedelicsFast-spiking cellsParvalbumin interneuronsGABAergic interneuronsVHPCFiring rateDOIHippocampusInterneuronsTherapeutic potentialReceptorsPsychedelicsCellular triggersGenetic approachesElectrophysiology
2020
Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons
Pothula S, Liu RJ, Wu M, Sliby AN, Picciotto MR, Banerjee P, Duman RS. Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons. Neuropsychopharmacology 2020, 46: 799-808. PMID: 33059355, PMCID: PMC8027594, DOI: 10.1038/s41386-020-00882-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMedial prefrontal cortexRapid antidepressant-like effectsGluN2B-containing NMDARsPositive allosteric modulatorsNMDAR positive allosteric modulatorExcitatory neuronsExerts antidepressant-like effectsAntidepressant-like behavioral effectsPrefrontal cortexBehavioral effectsAkt/mTORAntidepressant-like actionChronic unpredictable stressNMDA receptor activityRecent preclinical studiesMajor depressive disorderSpecific knockdownParvalbumin inhibitory neuronsCellular triggersSynaptic proteinsGlutamatergic systemNMDAR activityClinical trialsDepressive disorderCell-type specific modulation of NMDA receptors triggers antidepressant actions
Pothula S, Kato T, Liu RJ, Wu M, Gerhard D, Shinohara R, Sliby AN, Chowdhury GMI, Behar KL, Sanacora G, Banerjee P, Duman RS. Cell-type specific modulation of NMDA receptors triggers antidepressant actions. Molecular Psychiatry 2020, 26: 5097-5111. PMID: 32488125, DOI: 10.1038/s41380-020-0796-3.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsNMDAR positive allosteric modulatorMedial prefrontal cortexAntidepressant effectsAntidepressant actionGlutamate effluxReceptor positive allosteric modulatorPrincipal glutamatergic neuronsAction of ketamineAntidepressant-like effectsRapid antidepressant effectsRapid antidepressant actionsSimilar antidepressant effectsSpecific knockdownCell type-specific modulationCellular triggersGABA interneuronsGlutamate releaseGlutamatergic neuronsPyramidal neuronsNMDAR antagonistsNMDAR activityNMDAR functionExcitatory synapsesCell type-specific rolesGABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions
Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, Taylor SR, Duman CH, Delpire E, Picciotto M, Wohleb ES, Duman RS. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. Journal Of Clinical Investigation 2020, 130: 1336-1349. PMID: 31743111, PMCID: PMC7269589, DOI: 10.1172/jci130808.Peer-Reviewed Original ResearchConceptsRapid antidepressant actionsAntidepressant actionGABA interneuronsMedial prefrontal cortexCell-specific knockdownPrinciple neuronsPrefrontal cortexDeletion of GluN2BSingle subanesthetic doseBehavioral actionsAction of ketamineNMDA receptor antagonistExcitatory postsynaptic currentsCellular triggersMajor unmet needKetamine's rapid antidepressant actionsGABA subtypeGluN2B-NMDARsSST interneuronsPostsynaptic currentsReceptor antagonistDepressed patientsSubanesthetic doseExtracellular glutamateMood disorders
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