Cannabinoid Modulation of Cortical Synaptic Transmission
大麻素对皮质突触传递的调节
基本信息
- 批准号:7225484
- 负责人:
- 金额:$ 20.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-08-01 至 2010-04-30
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAgonistAreaBindingCNR1 geneCannabinoidsCellsCerebellumCerebral cortexCholecystokininChromosome PairingClassCognitiveComputer information processingCoupledDataDistalEndocannabinoidsFire - disastersG-Protein-Coupled ReceptorsGenerationsGoalsHippocampus (Brain)InterneuronsLaboratoriesLanguageLigandsMediatingMental DepressionMotorMuscarinic Acetylcholine ReceptorNeocortexOutputPatternPeptidesPerceptionPhysiologicalPlayPopulationPresynaptic TerminalsProcessProsencephalonPyramidal CellsRangeRateReceptor ActivationRegulationResearchResearch PersonnelRoleSensorySensory ProcessSignal TransductionSpatial DistributionSpecificityStructureSynapsesSynaptic TransmissionSystemTestingThinkingTimeWeltsWhole-Cell Recordingscell cortexcell typegamma-Aminobutyric Acidhippocampal pyramidal neuronin vivoneocorticalneuronal cell bodypostsynapticpresynapticprogramsreceptorresearch studysynaptic inhibition
项目摘要
DESCRIPTION (provided by applicant): The cerebral cortex is involved in a huge diversity of function, ranging from sensory processing and motor coordination to perception, generation of language, aM other higher-order cognitive abilities. These varied processes rely on the function of pyramidal cells, which are responsible for connections between cortical areas as well as connections to subcortical structures. Pyramidal cell activity, in turn, is tightly controlled by distinct classes of GABAergic inhibitory interneurons, which innervate functionally segregated domains on pyramidal cells to regulate action potential timing, the efficacy of excitatory inputs, and synchronous activity. These interneurons fire at high rates in vivo and provide potent inhibition to pyramidal cells, thus regulation of this inhibitory tone is essential for proper cortical function. Recent anatomical and physiological data indicate that the cannabinoid system plays an important role in modulating GABAergic interneurons in the neocortex. The type 1 cannabinoid (CB 1) receptor is one of the most highly expressed G-protein coupled receptors in the forebrain, and mediates the effects of exogenous cannabinoids on cognitive, sensory, and motor processes. Endogenous cannabinoid ligands are synthesized and released from pyramidal neurons with a high degree of spatial and temporal specificity, and act at least in part by binding to receptors on the presynaptic terminals of interneurons to regulate GABA release. The specificity of the endogenous system suggests that the disruptive effects of exogenous cannabinoids on cognitive processes may result from the non-selective global activation of this system. The long-term objective of this research is to understand the physiological significance of endogenous cannabinoid signaling in the regulation of neocortical function. The specific goals of the proposed studies are to: 1) determine the impact of endogenous cannabinoids on cortical synaptic inhibition, 2) test the hypothesis that cannabinoids selectively modulate a particular functional class of inhibitory afferents to pyramidal cells, and 3) investigate the consequences of cannabinoid signaling for pyramidal cell activity.
描述(由申请人提供):大脑皮层涉及各种各样的功能,从感觉处理和运动协调到感知、语言生成和其他高级认知能力。这些不同的过程依赖于锥体细胞的功能,锥体细胞负责皮层区域之间的连接以及与皮层下结构的连接。反过来,锥体细胞的活动受到不同类别的GABA能抑制性中间神经元的严格控制,这些抑制性中间神经元支配锥体细胞上功能分离的结构域,以调节动作电位计时、兴奋性输入的功效和同步活动。这些中间神经元在体内以高速率放电,并对锥体细胞提供有效的抑制,因此这种抑制性音调的调节对于适当的皮质功能是必不可少的。最近的解剖学和生理学数据表明,大麻素系统在调节新皮层中的GABA能中间神经元中起重要作用。1型大麻素(CB 1)受体是前脑中最高表达的G蛋白偶联受体之一,并介导外源性大麻素对认知、感觉和运动过程的影响。内源性大麻素配体以高度的空间和时间特异性从锥体神经元合成和释放,并且至少部分地通过与中间神经元的突触前末端上的受体结合来调节GABA释放而起作用。内源性系统的特异性表明,外源性大麻素对认知过程的破坏性影响可能是由于该系统的非选择性全局激活造成的。本研究的长期目标是了解内源性大麻素信号在调节新皮质功能中的生理意义。拟议研究的具体目标是:1)确定内源性大麻素对皮质突触抑制的影响,2)测试大麻素选择性调节锥体细胞抑制性传入的特定功能类别的假设,以及3)研究大麻素信号传导对锥体细胞活性的影响。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cannabinoid modulation of backpropagating action potential-induced calcium transients in layer 2/3 pyramidal neurons.
大麻素对 2/3 层锥体神经元反向传播动作电位诱导的钙瞬变的调节。
- DOI:10.1093/cercor/bhs168
- 发表时间:2013
- 期刊:
- 影响因子:0
- 作者:Hsieh,LawrenceS;Levine,EricS
- 通讯作者:Levine,EricS
Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ-aminobutyric acid type B receptor activity.
海马 CA1 区的癫痫样活性变得难以被大麻素减弱,部分原因是内源性 γ-氨基丁酸 B 型受体活性。
- DOI:10.1002/jnr.23027
- 发表时间:2012
- 期刊:
- 影响因子:4.2
- 作者:Messer,RickaD;Levine,EricS
- 通讯作者:Levine,EricS
Endocannabinoids mediate rapid retrograde signaling at interneuron right-arrow pyramidal neuron synapses of the neocortex.
内源性大麻素介导新皮质中间神经元右箭头锥体神经元突触的快速逆行信号传导。
- DOI:10.1152/jn.01037.2002
- 发表时间:2003
- 期刊:
- 影响因子:2.5
- 作者:Trettel,Joseph;Levine,EricS
- 通讯作者:Levine,EricS
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Eric S Levine其他文献
Eric S Levine的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
$ 20.62万 - 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:
$ 20.62万 - 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:
$ 20.62万 - 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:
10531584 - 财政年份:2019
- 资助金额:
$ 20.62万 - 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:
$ 20.62万 - 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:
$ 20.62万 - 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:
$ 20.62万 - 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:
$ 20.62万 - 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:
$ 20.62万 - 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:
$ 20.62万 - 项目类别:
相似国自然基金
Agonist-GPR119-Gs复合物的结构生物学研究
- 批准号:32000851
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
相似海外基金
S1PR1 agonistによる脳血液関門制御を介した脳梗塞の新規治療法開発
S1PR1激动剂调节血脑屏障治疗脑梗塞新方法的开发
- 批准号:
24K12256 - 财政年份:2024
- 资助金额:
$ 20.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
AHR agonistによるSLE皮疹の新たな治療薬の開発
使用 AHR 激动剂开发治疗 SLE 皮疹的新疗法
- 批准号:
24K19176 - 财政年份:2024
- 资助金额:
$ 20.62万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Evaluation of a specific LXR/PPAR agonist for treatment of Alzheimer's disease
特定 LXR/PPAR 激动剂治疗阿尔茨海默病的评估
- 批准号:
10578068 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
- 批准号:
10933287 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
Targeting breast cancer microenvironment with small molecule agonist of relaxin receptor
用松弛素受体小分子激动剂靶向乳腺癌微环境
- 批准号:
10650593 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
AMPKa agonist in attenuating CPT1A inhibition and alcoholic chronic pancreatitis
AMPKa 激动剂减轻 CPT1A 抑制和酒精性慢性胰腺炎
- 批准号:
10649275 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253
在男性和女性健康志愿者中进行的一项随机双盲安慰剂对照 1 期 SAD 研究,旨在评估 ABCA1 激动剂 CS6253 的安全性、药代动力学和短暂生物标志物变化
- 批准号:
10734158 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation
研究阿片类激动剂治疗 OUD 患者结果的机制:解开睡眠和昼夜节律对渴望和情绪调节的影响
- 批准号:
10784209 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
A novel nanobody-based agonist-redirected checkpoint (ARC) molecule, aPD1-Fc-OX40L, for cancer immunotherapy
一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
- 批准号:
10580259 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
Identification and characterization of a plant growth promoter from wild plants: is this a novel plant hormone agonist?
野生植物中植物生长促进剂的鉴定和表征:这是一种新型植物激素激动剂吗?
- 批准号:
23K05057 - 财政年份:2023
- 资助金额:
$ 20.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)