Regulation Of Mood By Dopamine D1 Receptors On Cerebral Cortical Interneurons
Regulation Of Mood By Dopamine D1 Receptors On Cerebral Cortical Interneurons
批准号:
9752659
负责人:
GREGG D STANWOOD
金额:
$19.25万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-08-01 至 2021-06-30
关键词:
AddressAdultAffectAnhedoniaAnimal ModelAntidepressive AgentsBehaviorBehavioralBrainBrain DiseasesBrain-Derived Neurotrophic FactorCaringCellsCerebral cortexCerebrumChronic DiseaseCognitive TherapyConsumptionDataDecision MakingDevelopmentDiseaseDopamineDopamine D1 ReceptorDopamine D2 ReceptorDown-RegulationEnterobacteria phage P1 Cre recombinaseEnvironmentEpigenetic ProcessExhibitsExtracellular Matrix ProteinsFoundationsFunctional disorderGangliaGene ExpressionGeneticGenetic Enhancer ElementGenetic RecombinationGlutamatesIndividualInflammationInterneuronsKnock-outKnockout MiceLaboratoriesLeadLiquid substanceMajor Depressive DisorderMeasuresMedialMental DepressionModelingMolecularMonoamine Oxidase InhibitorsMoodsMotivationMusNeuroendocrinologyNeuronal PlasticityNeuronsNeurotransmittersPalateParvalbuminsPatientsPharmaceutical PreparationsPharmacological TreatmentPharmacologyPharmacotherapyPhenotypePositioning AttributePreventionProcessPsychotherapyReceptor SignalingRewardsRoleSeriesSerotonin Uptake InhibitorsSex DifferencesShort-Term MemorySignal PathwaySignal TransductionSomatostatinStressStructureSyndromeTail SuspensionTamoxifenTestingTherapeuticWomanantidepressant effectbasebehavior measurementbiological adaptation to stressburden of illnesscell typedepression modeldisturbance in affectexecutive functionfeedingforced swim testfrontal lobegamma-Aminobutyric Acidgene environment interactioninnovationinterestmenmonoaminemood regulationmotor controlneuroadaptationneuropsychiatrynew therapeutic targetnovelnovel therapeutic interventionpromoterreceptorrecombinase-mediated cassette exchangerelating to nervous systemresilienceresponserestraintside effectsocial defeatstressorsuccesstherapeutic target
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
We recently used the Cre/loxP system to selectively delete dopamine D1 receptors from GABAergic neurons
from the Nkx2.1 lineage within the medial ganglionic eminence. These cells largely produce a subset of crucial
cerebral cortical interneurons within the medial frontal cortex. Although these interneuron-localized receptors
represent just a small fraction of cortical dopamine D1 receptors (most are on excitatory glutamatergic projection
neurons), these conditional knockout mice exhibit a remarkable phenotype in one functional domain – mood.
Specifically, GABA-D1-cKO mice exhibit decreased immobility in the forced swim test, and decreased latency to
consume a palatable liquid in a novel stressful environment; these are both indicative of an antidepressant-like
effect. These data suggest a new mechanism by which cerebral cortical interneurons may contribute to mood
regulation, and importantly, this mechanism may be “druggable”. The current proposal seeks to validate this
model using additional behavioral measures and stressors (Aim 1), define the developmental timing components
of this neuroadaptation (Aim 2), and begin to assess the cellular and molecular underpinnings of this response
(Aim 3). Success of this current project will position us to subsequently develop unique therapeutic strategies to
selectively manipulate these receptors through genetic and pharmacological approaches that are limited to
specific neuronal subpopulations.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Dopaminergic Modulation of Brain Development
-
批准号:8465275
-
项目类别:
-
资助金额:$37.07万
-
财政年份:2010
-
负责人:GREGG D STANWOOD
-
依托单位:
Dopaminergic Modulation of Brain Development
-
批准号:7985721
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项目类别:
-
资助金额:$36.55万
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财政年份:2010
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负责人:GREGG D STANWOOD
-
依托单位:
Dopaminergic Modulation of Brain Development
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批准号:8101969
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项目类别:
-
资助金额:$37.97万
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财政年份:2010
-
负责人:GREGG D STANWOOD
-
依托单位:
Dopaminergic Modulation of Brain Development
-
批准号:8658726
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项目类别:
-
资助金额:$38.61万
-
财政年份:2010
-
负责人:GREGG D STANWOOD
-
依托单位:
Dopaminergic Modulation of Brain Development
-
批准号:8257967
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项目类别:
-
资助金额:$38.61万
-
财政年份:2010
-
负责人:GREGG D STANWOOD
-
依托单位:
Dopaminergic Influences on Brain Formation and Function
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批准号:7022952
-
项目类别:
-
资助金额:$7.45万
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财政年份:2005
-
负责人:GREGG D STANWOOD
-
依托单位:
Dopaminergic Influences on Brain Formation and Function
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批准号:6924139
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项目类别:
-
资助金额:$7.58万
-
财政年份:2005
-
负责人:GREGG D STANWOOD
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依托单位:
海外基金