Susumu Tomita, PhD
Professor of Cellular and Molecular Physiology and NeuroscienceCards
Appointments
Contact Info
About
Titles
Professor of Cellular and Molecular Physiology and Neuroscience
Appointments
Cellular & Molecular Physiology
ProfessorFully JointNeuroscience
ProfessorFully Joint
Other Departments & Organizations
- Cellular & Molecular Physiology
- Graduate Program in Cellular and Molecular Physiology
- Interdepartmental Neuroscience Program
- Kavli Institute for Neuroscience
- Molecular Medicine, Pharmacology, and Physiology
- Neuroscience
- Neuroscience Track
- Program in Cellular Neuroscience, Neurodegeneration and Repair
- Wu Tsai Institute
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- Postdoctoral fellowship
- UCSF (2005)
- PhD
- University of Tokyo (2000)
Research
Overview
My laboratory’s approach to understand brain is to reduce brain to various components and ultimately molecules. The primary functional component of brain is the neural circuit, which are comprised of anatomical neuronal wiring and synaptic transmission. Temporally, neurotransmission by a major excitatory neurotransmitter in brain, glutamate, is very quick and is clearly essential for brain function; however, the modulation of brain function underlying learning, memory, emotion, cognition, etc., happens on a different time scale than that of neurotransmission. Our broad goal is to understand how basic synaptic transmission can be modulated over seconds to hours, thereby supporting complex brain functions.The efficacy of synaptic transmission is determined by glutamate concentration at the synaptic cleft and by the number and channel properties of the glutamate receptors, which can be modulated by neuronal activation (synaptic plasticity).
It is therefore important to determine how many receptors are at synapses and how strongly these receptors are activated upon glutamate releases. We have uncovered a network of modulatory proteins for glutamate receptors to control their number and properties. By understanding the machinery that controls the number and channel properties of glutamate receptors, we hope to reveal the principal rules governing synaptic transmission and synaptic plasticity. Combined with neuronal wiring mapping, this should help us understand a big picture of neural circuits and the momentary changes that occur in neural circuits to control animal behavior.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Chiayu Chiu, PhD
Erika Hoyos-Ramirez, PhD
Marina Picciotto, PhD
Michael J Higley, MD/PhD
Yann Mineur, MS, PhD
Synaptic Transmission
Brain
Publications
2024
Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula–interpeduncular nucleus pathway in mice
Tsuzuki A, Yamasaki M, Konno K, Miyazaki T, Takei N, Tomita S, Yuzaki M, Watanabe M. Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula–interpeduncular nucleus pathway in mice. Scientific Reports 2024, 14: 14193. PMID: 38902419, PMCID: PMC11189931, DOI: 10.1038/s41598-024-65076-3.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsMHb-IPN pathwayMHb neuronsNicotine dependenceNicotinic acetylcholine receptorsAcetylcholine receptorsNicotine-related behaviorsCell surfaceImmunoelectron microscopySubunitAxonal compartmentFunctional roleNeurotransmitter releasePresynaptic terminalsSubcellular expressionPathwaySimultaneous detectionDistribution patternsSynaptic junctionsNAChRsAnatomical basisExpressionNegative controlReceptorsNeuronsAntibodies3-Hydroxykynurenine targets kainate receptors to promote defense against infection
Parada-Kusz M, Clatworthy A, Goering E, Blackwood S, Shigeta J, Mashin E, Salm E, Choi C, Combs S, Lee J, Rodriguez-Osorio C, Clish C, Tomita S, Hung D. 3-Hydroxykynurenine targets kainate receptors to promote defense against infection. Nature Chemical Biology 2024, 1-11. PMID: 38898166, DOI: 10.1038/s41589-024-01635-z.Peer-Reviewed Original ResearchCitationsAltmetricConceptsKainate-sensitive glutamate receptorsHost tryptophan metabolismHost survivalBacterial infectionsPromote host survivalGlutamate receptorsLethal bacterial infectionHost-pathogenIn vivo chemical screeningTryptophan metabolismPromote defenseBacterial expansionOutcome of infectionChemical screeningZebrafish embryosAntibacterial activityKainate receptorsPathogen eradicationPathogensHostModulate immunityNervous systemInfectionMetabolismReceptors
2023
Chemogenetic 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsGlutamatergic Pathways and Receptors
Tomita S. Glutamatergic Pathways and Receptors. 2023, 197-200. DOI: 10.1007/978-3-031-15070-8_30.Peer-Reviewed Original ResearchConceptsGlutamate 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 channels
2022
P-088 Radiosynthesis of 6-(2-cyclobutyl-5-(methyl-11C)-3H-imidazo[4,5-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one and (2-cyclobutyl-3-(1H-indazol-5-yl)-5-[11C]methyl-3H-imidazo[4,5-b]pyridine for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein
Yu Q, Kumata K, Collier T, Tomita S, Zhang M, Liang S. P-088 Radiosynthesis of 6-(2-cyclobutyl-5-(methyl-11C)-3H-imidazo[4,5-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one and (2-cyclobutyl-3-(1H-indazol-5-yl)-5-[11C]methyl-3H-imidazo[4,5-b]pyridine for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein. Nuclear Medicine And Biology 2022, 108: s97-s98. DOI: 10.1016/s0969-8051(22)00225-6.Peer-Reviewed Original Research
2019
Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation
McCarroll MN, Gendelev L, Kinser R, Taylor J, Bruni G, Myers-Turnbull D, Helsell C, Carbajal A, Rinaldi C, Kang HJ, Gong JH, Sello JK, Tomita S, Peterson RT, Keiser MJ, Kokel D. Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation. Nature Communications 2019, 10: 4078. PMID: 31501447, PMCID: PMC6733874, DOI: 10.1038/s41467-019-11936-w.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsParadoxical excitationGABAA receptorsCentral nervous system depressantsSerotonin 6 receptorMost anesthetic drugsDifferent neuronal targetsHuman GABAA receptorsNeuronal targetsNeuronal activityAnesthetic drugsMotor activitySerotonin receptor ligandsSedationReceptor ligandsReceptorsCaudal hindbrainAnestheticsPrimary targetPrevious studiesGABATargetNeuronsActivityBrainMolecular constituents and localization of the ionotropic GABA receptor complex in vivo
Tomita S. Molecular constituents and localization of the ionotropic GABA receptor complex in vivo. Current Opinion In Neurobiology 2019, 57: 81-86. PMID: 30784980, PMCID: PMC6629498, DOI: 10.1016/j.conb.2019.01.017.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNative receptor complexReceptor complexPore-forming subunitMolecular constituentsNew mechanistic insightsProtein familySubunit assemblyMajor molecular constituentsProperties of GABASynaptic localizationIonotropic GABA receptorsPrimary neuronsMechanistic insightsGABA receptor complexNative GABAReceptor regulationGABA receptorsNeuroligin-2R complexesGABAFast inhibitionPharmacological propertiesComplexesLocalizationSubunits
2018
Unexplored therapeutic opportunities in the human genome.
Oprea TI, Bologa CG, Brunak S, Campbell A, Gan GN, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J, Jadhav A, Jensen LJ, Johnson GL, Karlson A, Leach AR, Ma'ayan A, Malovannaya A, Mani S, Mathias SL, McManus MT, Meehan TF, von Mering C, Muthas D, Nguyen DT, Overington JP, Papadatos G, Qin J, Reich C, Roth BL, Schürer SC, Simeonov A, Sklar LA, Southall N, Tomita S, Tudose I, Ursu O, Vidovic D, Waller A, Westergaard D, Yang JJ, Zahoránszky-Köhalmi G. Unexplored therapeutic opportunities in the human genome. Nature Reviews. Drug Discovery 2018, 17: 377. PMID: 29567993, DOI: 10.1038/nrd.2018.52.Peer-Reviewed Original ResearchInput-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition
Chiu CQ, Martenson JS, Yamazaki M, Natsume R, Sakimura K, Tomita S, Tavalin SJ, Higley MJ. Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition. Neuron 2018, 97: 368-377.e3. PMID: 29346754, PMCID: PMC5777295, DOI: 10.1016/j.neuron.2017.12.032.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDendritic inhibitionInput-specific long-term potentiationNMDA-type glutamate receptorsGABAergic inhibitory synapsesSomatostatin-expressing interneuronsGABA-A receptorsNormal brain functionLong-term potentiationForms of plasticityHomeostatic cellular mechanismsGABAergic inhibitionSynaptic excitationPerisomatic inhibitionPostsynaptic spikingInhibitory synapsesLong-term plasticityGlutamate receptorsInhibitory inputsSynaptic transmissionDependent potentiationCortical circuitsGenetic deletionBrain functionNeuronal dendritesCellular mechanisms
2017
Assembly rules for GABAA receptor complexes in the brain
Martenson JS, Yamasaki T, Chaudhury NH, Albrecht D, Tomita S. Assembly rules for GABAA receptor complexes in the brain. ELife 2017, 6: e30826. PMID: 28816653, PMCID: PMC5577914, DOI: 10.7554/elife.27443.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
Academic Achievements and Community Involvement
honor Alfred P. Sloan Research Fellowship Award
Regional AwardAlfred P. Sloan Research FoundationDetails01/01/2007United Stateshonor NARSAD Young Investigator Award
Regional AwardNARSADDetails01/01/2007United Stateshonor Klingenstein Fellowship Awards In The Neurosciences
Regional AwardThe Esher and Joseph Klingenstein FoundationDetails01/01/2006United States
Links & Media
Media
- A, TARPs consist of four isoforms (stargazin, g -3, g -4, and g -8), which show distinct expression patterns in the brain . B, TARPs (green) colocalize with the glutamatergic markers AMPA receptors (red)(left panel), but not with the GABAergic marker GAD65 (red)(right panel). C, TARPs both modulate trafficking of AMPA receptors to the synapses and control the gating and pharmacology of the channel. Oocytes injected with GluR1 alone are more sensitive to glutamate (Glu) than to kainate (KA). D, AMPA receptor subunits GluR1, GluR2 and GluR4 co-immunoprecipitate with stargazin (STG) in brain extracts from +/stg mice (+/-), but not in extracts from stg/stg mice (-/-). E, TARPs stabilize AMPA receptors at synapses through its C-terminal PDZ domain binding motif.
News
- April 17, 2023
Seo & Belfort De Aguiar, and Yogev & Tomita Honored With 2023 Kavli Innovative Research Awards
- January 09, 2020
Cellular and Molecular Physiology Annual Retreat 2019
- December 06, 2018
Cellular and Molecular Physiology Annual Retreat 2018
- October 02, 2017
Cellular and Molecular Physiology Annual Retreat 2017
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