Serotonergic modulation of the circuits and cell-types of the lateral habenula
外侧缰核电路和细胞类型的血清素调节
基本信息
- 批准号:10713125
- 负责人:
- 金额:$ 62.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:Action PotentialsAcuteAffectAnhedoniaAntidepressive AgentsArousalAxonBehaviorBehavioralBrainBrain regionCalciumCellsChronic stressColorDataDiseaseDopamineElectrophysiology (science)EmotionalExhibitsFire - disastersFoundationsG-Protein-Coupled ReceptorsGenesHabenulaHeadHumanHyperactivityIn VitroIndividualIon ChannelLateralLearningLinkLongitudinal StudiesMajor Depressive DisorderMeasuresMediatorMental DepressionMental disordersMethodsMidbrain structureMusNeuromodulatorNeuronsNorepinephrineOpticsOutcomePatternPharmaceutical PreparationsPharmacologic SubstanceProsencephalonPsychiatric therapeutic procedurePsychological reinforcementReportingRodent ModelSelective Serotonin Reuptake InhibitorSerotoninStressStructureSynapsesSynaptic TransmissionTechniquesTestingTherapeuticTherapeutic InterventionTimeWorkbehavioral phenotypingcell typecognitive processcommon treatmentdifferential expressionfluorophorehindbrainimprovedin vivomemory processmotivated behaviormotor controlnervous system disorderneural circuitneuronal circuitryreceptorsensorserotonin receptorspatiotemporaltranscriptometranscriptomics
项目摘要
Project Summary
Serotonin (5-HT)-releasing neurons in the mammalian mid/hindbrain are critical for fundamental behaviors and
cognitive processes, including emotional control, arousal, and motor control. Selective serotonin reuptake
inhibitors (SSRIs) increase brain 5-HT levels and are the most commonly prescribed treatment for major-
depression in humans. However, our understanding of the mechanisms by which 5-HT influences synapses,
cells, and circuits is limited, prohibiting improvement of depression therapeutics. A major target of 5-HT
neurons is the lateral habenula (LHb), a subcortical structure principally implicated in evaluating the outcome
(positive or negative) of an action. The LHb is the only brain region that shows consistent hyperactivity several
rodent models of chronic stress and additional studies have recently refined this observation indicating “burst-
firing” in LHb is causally related several behavioral phenotypes (including anhedonia) following chronic stress.
Recently, using single-cell transcriptome wide sequencing, we genetically defined the neuronal subclasses
within the LHb for the first time revealing cell-type specific expression of both 5-HT receptors and genes
related to burst-firing. Our central hypothesis is that 5-HT release dynamically modulates the habenula circuit
though neuron-type specific expression of 5-HT receptors and that burst-firing in specific, genetically defined
LHb neuron-types is required for anhedonia following chronic stress. This proposal seeks to 1) identify the
neuron-type(s) in the LHb that exhibit burst-firing in vitro and in vivo, 2) determine how 5-HT modulates
neuron-types and local connectivity within the LHb and 3) define the neuron-types in the LHb required for
chronic stress induced anhedonia. By revealing how 5-HT modulates habenular circuits, the proposed work
will provide a comprehensive understanding of the cellular and circuit targets of this important neuromodulator.
These findings will form the foundation for understanding the principal mechanisms by which SSRIs impact
synapses and circuits of the LHb, uncovering new avenues for therapeutic intervention in major depressive
disorder and other neurological disorders treated by these drugs.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael L Wallace其他文献
Michael L Wallace的其他文献
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{{ truncateString('Michael L Wallace', 18)}}的其他基金
A function for the Entopeduncular Nucleus In Motivated Behavior
内脚核在动机行为中的功能
- 批准号:
10346112 - 财政年份:2018
- 资助金额:
$ 62.04万 - 项目类别:
A function for the Entopeduncular Nucleus In Motivated Behavior
内脚核在动机行为中的功能
- 批准号:
10378070 - 财政年份:2018
- 资助金额:
$ 62.04万 - 项目类别:
A Function for the Entopeduncular Nucleus in Motivated Behavior
内脚核在动机行为中的功能
- 批准号:
10553248 - 财政年份:2018
- 资助金额:
$ 62.04万 - 项目类别:
Cell Type-Specific Synaptic Defects in Angelman Syndrome Model Mice
安杰曼综合征模型小鼠细胞类型特异性突触缺陷
- 批准号:
8256078 - 财政年份:2011
- 资助金额:
$ 62.04万 - 项目类别:
Cell Type-Specific Synaptic Defects in Angelman Syndrome Model Mice
安杰曼综合征模型小鼠细胞类型特异性突触缺陷
- 批准号:
8340567 - 财政年份:2011
- 资助金额:
$ 62.04万 - 项目类别:
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