Regulation of synaptic plasticity by BDNF-endocannabinoid interactions
BDNF-内源性大麻素相互作用对突触可塑性的调节
基本信息
- 批准号:10531584
- 负责人:
- 金额:$ 54.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-12-01 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:2-arachidonylglycerolAcuteAffectAnxietyAreaBrainBrain-Derived Neurotrophic FactorCNR1 geneCalciumCell LineCoupledDataDevelopmentDiseaseElectrophysiology (science)EndocannabinoidsEngineeringEpilepsyEquilibriumExcitatory SynapseExhibitsFunctional disorderGlutamatesGoalsHippocampusHumanImageImpairmentIndividualInduced pluripotent stem cell derived neuronsInhibitory SynapseKnowledgeLong-Term DepressionLong-Term PotentiationMediatingMemoryMental DepressionMental disordersMetabolismMolecularMonitorMotorMultiple SclerosisMusNeocortexNeuronal DifferentiationNeuronsNeurotrophic Tyrosine Kinase Receptor Type 2PerceptionPhenotypePhysiological ProcessesPlayPopulationPrefrontal CortexProsencephalonPyramidal CellsRegulationRoleSchizophreniaSensorySignal TransductionSingle Nucleotide PolymorphismSliceSomatosensory CortexSynapsesSynaptic PotentialsSynaptic plasticitySystemanandamideautism spectrum disordercognitive abilityendocannabinoid signalingexperimental studygamma-Aminobutyric Acidgenetic approachimmunocytochemistryinduced pluripotent stem cellinsightneocorticalnervous system disorderneuroregulationneurotrophic factornovel therapeutic interventionnovel therapeuticspainful neuropathypatch clamppermissivenesspharmacologicpostsynapticpresynapticrelease factortranslational impacttranslational potential
项目摘要
PROJECT SUMMARY
The goal of this project is to explore the functional relevance of interactions between brain-derived neurotrophic
factor (BDNF) and endogenous cannabinoids (eCB) in regulating activity-dependent synaptic plasticity in the
neocortex and hippocampus. Although there is growing evidence for crosstalk between BDNF and eCBs, little is
known regarding potential synaptic interactions. We have previously characterized the synaptic effects of eCBs
and BDNF in layer 2/3 and layer 5 of somatosensory cortex as well as the CA1 area of hippocampus, and we
have recently shown that the presynaptic effects of BDNF at cortical and hippocampal inhibitory synapses are
mediated by the BDNF-induced release of eCBs from postsynaptic pyramidal cells. We have also found that
BDNF causes release of eCBs at excitatory synapses, and this eCB signaling mitigates the direct facilitatory
effects of BDNF at these synapses. We are now poised to explore the functional relevance of these interactions
in regulating activity-dependent synaptic plasticity. In particular, we will examine the interactions between
endogenous BDNF-induced eCB release and activity-dependent eCB release in regulating the magnitude and
direction of plasticity at excitatory and inhibitory synapses. These studies will combine electrophysiology and
calcium imaging with pharmacological and genetic approaches to manipulate these signaling systems. We will
also examine these signaling interactions using mice engineered to express common human single-nucleotide
polymorphisms (SNPs) that affect either endogenous BDNF or anandamide levels. Importantly, we will carry out
parallel studies using cultured human induced pluripotent stem cell (iPSC)-derived neurons generated from
individuals who carry these same SNPs.
项目摘要
本项目的目标是探索脑源性神经营养因子与神经营养因子之间相互作用的功能相关性。
内源性大麻素(eCB)在调节活动依赖性突触可塑性中的作用
新皮层和海马体。虽然有越来越多的证据表明BDNF和eCB之间存在串扰,但很少有证据表明,
关于潜在的突触相互作用。我们先前已经描述了eCB的突触效应
和BDNF在躯体感觉皮层2/3层和5层以及海马CA 1区的表达,
最近的研究表明,BDNF在皮层和海马抑制性突触的突触前作用,
由BDNF诱导的eCB从突触后锥体细胞的释放介导。我们还发现
BDNF导致兴奋性突触释放eCB,这种eCB信号传导减轻了直接的易化作用。
BDNF对这些突触的影响。我们现在准备探索这些相互作用的功能相关性
在调节活动依赖性突触可塑性方面。特别是,我们将研究
内源性BDNF诱导的eCB释放和活性依赖性eCB释放在调节
兴奋性和抑制性突触可塑性的方向。这些研究将结合联合收割机电生理学和
钙成像与药理学和遗传学的方法来操纵这些信号系统。我们将
我还使用基因工程小鼠来检测这些信号相互作用,
基因多态性(SNP)影响内源性BDNF或大麻素水平。重要的是,我们将执行
使用培养的人诱导多能干细胞(iPSC)衍生的神经元进行的平行研究,
携带相同SNPs的个体。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hyperexcitable Phenotypes in Induced Pluripotent Stem Cell-Derived Neurons From Patients With 15q11-q13 Duplication Syndrome, a Genetic Form of Autism.
- DOI:10.1016/j.biopsych.2021.07.018
- 发表时间:2021-12-01
- 期刊:
- 影响因子:10.6
- 作者:Fink JJ;Schreiner JD;Bloom JE;James J;Baker DS;Robinson TM;Lieberman R;Loew LM;Chamberlain SJ;Levine ES
- 通讯作者:Levine ES
2-AG and anandamide enhance hippocampal long-term potentiation via suppression of inhibition.
- DOI:10.3389/fncel.2022.1023541
- 发表时间:2022
- 期刊:
- 影响因子:5.3
- 作者:
- 通讯作者:
The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons.
- DOI:10.1016/j.stemcr.2023.02.002
- 发表时间:2023-04-11
- 期刊:
- 影响因子:5.9
- 作者:Elamin, Marwa;Dumarchey, Aurelie;Stoddard, Christopher;Robinson, Tiwanna M.;Cowie, Christopher;Gorka, Dea;Chamberlain, Stormy J.;Levine, Eric S.
- 通讯作者:Levine, Eric S.
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Eric S Levine其他文献
Eric S Levine的其他文献
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{{ truncateString('Eric S Levine', 18)}}的其他基金
Contribution of GABA-A receptor subunit deletions to Angelman syndrome pathophysiology
GABA-A 受体亚基缺失对 Angelman 综合征病理生理学的贡献
- 批准号:
10391880 - 财政年份:2021
- 资助金额:
$ 54.11万 - 项目类别:
Regulation of synaptic plasticity by BDNF-endocannabinoid interactions
BDNF-内源性大麻素相互作用对突触可塑性的调节
- 批准号:
10056991 - 财政年份:2019
- 资助金额:
$ 54.11万 - 项目类别:
Regulation of synaptic plasticity by BDNF-endocannabinoid interactions
BDNF-内源性大麻素相互作用对突触可塑性的调节
- 批准号:
9897089 - 财政年份:2019
- 资助金额:
$ 54.11万 - 项目类别:
Regulation of synaptic plasticity by BDNF-endocannabinoid interactions
BDNF-内源性大麻素相互作用对突触可塑性的调节
- 批准号:
10307088 - 财政年份:2019
- 资助金额:
$ 54.11万 - 项目类别:
Synaptic signaling in a human stem cell model of Angelman syndrome
天使综合征人类干细胞模型中的突触信号传导
- 批准号:
8415874 - 财政年份:2012
- 资助金额:
$ 54.11万 - 项目类别:
BDNF-Endocannabinoid Interactions in the Cerebral Cortex
大脑皮层中的 BDNF-内源性大麻素相互作用
- 批准号:
8660336 - 财政年份:2012
- 资助金额:
$ 54.11万 - 项目类别:
Synaptic signaling in a human stem cell model of Angelman syndrome
天使综合征人类干细胞模型中的突触信号传导
- 批准号:
8292528 - 财政年份:2012
- 资助金额:
$ 54.11万 - 项目类别:
BDNF-Endocannabinoid Interactions in the Cerebral Cortex
大脑皮层中的 BDNF-内源性大麻素相互作用
- 批准号:
8515525 - 财政年份:2012
- 资助金额:
$ 54.11万 - 项目类别:
BDNF-Endocannabinoid Interactions in the Cerebral Cortex
大脑皮层中的 BDNF-内源性大麻素相互作用
- 批准号:
9054927 - 财政年份:2012
- 资助金额:
$ 54.11万 - 项目类别:
BDNF-Endocannabinoid Interactions in the Cerebral Cortex
大脑皮层中的 BDNF-内源性大麻素相互作用
- 批准号:
8840657 - 财政年份:2012
- 资助金额:
$ 54.11万 - 项目类别:
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