Cellular basis of psilocybin actions in frontal cortex
额叶皮层裸盖菇素作用的细胞基础
基本信息
- 批准号:10516272
- 负责人:
- 金额:$ 59.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-19 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:Antidepressive AgentsApicalArchitectureAttentionBehaviorBehavioralBiologicalBrainChronic stressCognitionConsciousDendritic SpinesDoseExposure toGoalsHTR2A geneHalf-LifeHallucinogensHeadImageKetamineKnock-outMajor Depressive DisorderMeasuresMedialMediatingMental disordersMoodsMusNeocortexNeuronal PlasticityNeuronsPerceptionPyramidal TractsReceptor CellResolutionRodentSeriesSerotonin Receptor 5-HT2ASerotonin Receptor 5-HT2CSignal TransductionStressStructureTestingTherapeuticVertebral columnVirusantidepressant effectbasecell typeconditional knockoutdensityearly phase clinical trialexperimental studyfrontal lobehippocampal pyramidal neuronin vivoinsightneurobiological mechanismneuropsychiatric disordernoveloptical imagingreceptorrelating to nervous systemresponseretrograde transportserotonin receptortwo photon microscopytwo-photon
项目摘要
PROJECT SUMMARY
Psychedelics are compounds that produce an atypical state of consciousness characterized by altered
perception, cognition, and mood. Among psychedelics, psilocybin has gained attention recently because early
clinical trials indicated potential antidepressant effects, leading to a ‘breakthrough therapy’ designation from the
FDA to test psilocybin for major depressive disorder. However, despite the promise, the biological mechanisms
underpinning psilocybin’s potential therapeutic action are poorly understood. Our lab employs subcellular-
resolution two-photon microscopy to visualize dendritic structure and function in head-fixed mice. The goal of
this project is to characterize how a single dose of psilocybin may alter dendritic architecture in the medial
frontal cortex of the mouse and the associated cellular mechanisms. The hypothesis is that psilocybin
promotes spine formation by activating specific serotonin receptor subtypes and exerts differential effects on
distinct subtypes of pyramidal neurons. To test the hypothesis, we propose a series of experiments that
combine subcellular-resolution optical imaging, conditional knockouts, and causal perturbations in mice. The
results will answer crucial questions regarding psilocybin’s ability to promote structural plasticity in vivo and
delineate receptors and cellular factors that underlie the plasticity-promoting actions. We expect the
mechanistic insights will be important as the field evaluates psychedelics as a potential treatment option for
neuropsychiatric disorders and searches for novel antidepressants.
项目摘要
迷幻药是一种化合物,它能产生一种非典型的意识状态,
感知认知和情绪在致幻剂中,裸盖菇素最近引起了人们的关注,因为它在早期
临床试验显示了潜在的抗抑郁作用,导致了“突破性疗法”的命名。
FDA将测试裸盖菇素治疗重度抑郁症。然而,尽管有这样的希望,
对裸盖菇素潜在治疗作用的基础了解甚少。我们的实验室使用亚细胞-
分辨率双光子显微镜观察头部固定小鼠的树突结构和功能。的目标
这个项目是为了描述单剂量的裸盖菇素如何改变中膜树突的结构。
小鼠的额叶皮层和相关的细胞机制。假设裸盖菇素
通过激活特定的5-羟色胺受体亚型促进脊柱形成,
锥体神经元的不同亚型。为了验证这一假设,我们提出了一系列实验,
联合收割机结合亚细胞分辨率光学成像,条件性基因敲除,和因果扰动小鼠。的
结果将回答关于裸盖菇素促进体内结构可塑性的能力的关键问题,
描绘了促进可塑性作用的受体和细胞因子。我们预计
机械的见解将是重要的,因为该领域评估迷幻剂作为一种潜在的治疗选择,
神经精神疾病和寻找新的抗抑郁药。
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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CHUN-HAY ALEX KWAN其他文献
CHUN-HAY ALEX KWAN的其他文献
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{{ truncateString('CHUN-HAY ALEX KWAN', 18)}}的其他基金
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10755878 - 财政年份:2022
- 资助金额:
$ 59.83万 - 项目类别:
Cellular basis of psilocybin actions in frontal cortex
额叶皮层裸盖菇素作用的细胞基础
- 批准号:
10686230 - 财政年份:2022
- 资助金额:
$ 59.83万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10623145 - 财政年份:2022
- 资助金额:
$ 59.83万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10386910 - 财政年份:2020
- 资助金额:
$ 59.83万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10188646 - 财政年份:2020
- 资助金额:
$ 59.83万 - 项目类别:
Frontal cholinergic signals during value-based decision-making
基于价值的决策过程中的额叶胆碱能信号
- 批准号:
9789948 - 财政年份:2018
- 资助金额:
$ 59.83万 - 项目类别:
Structural plasticity basis of fast-acting antidepressant action
速效抗抑郁作用的结构可塑性基础
- 批准号:
9291526 - 财政年份:2016
- 资助金额:
$ 59.83万 - 项目类别:
Cortical GABAergic Circuits in Alzheimer's Disease
阿尔茨海默病中的皮质 GABA 能回路
- 批准号:
9293204 - 财政年份:
- 资助金额:
$ 59.83万 - 项目类别:
Cortical GABAergic Circuits in Alzheimer's Disease
阿尔茨海默病中的皮质 GABA 能回路
- 批准号:
8849045 - 财政年份:
- 资助金额:
$ 59.83万 - 项目类别:
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