The Physiology of Extra Synaptic NMDA Receptors
突触外 NMDA 受体的生理学
基本信息
- 批准号:7244067
- 负责人:
- 金额:$ 21.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-06-07 至 2009-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteBrainCalciumCell DeathCell SurvivalCell physiologyCessation of lifeCharacteristicsConditionCoupledDataDendritesDevelopmentElectrophysiology (science)FrequenciesHippocampus (Brain)IndividualKetamineLengthLocationLong-Term PotentiationMeasurementMeasuresMediatingMental DepressionN-Methyl-D-Aspartate ReceptorsN-MethylaspartateNeuronsNumbersPathway interactionsPhysiologicalPhysiologyPlayPopulationRattusReceptor ActivationRegulationRelative (related person)RoleSignal TransductionSliceSynapsesSynaptic ReceptorsSynaptic plasticityTestingTissuesWeekWorkbasehippocampal pyramidal neuronifenprodilphotolysispostnatalpresynapticreceptorresearch studysegregationsizesynaptogenesistransmission process
项目摘要
DESCRIPTION (provided by applicant): N-methyl-D-aspartate receptor (NMDAR) activation can result in both long and short-term plasticity, promote cell survival, initiate cell death, and is also critical for normal synaptogenesis during development. A number of studies suggest that the consequences of NMDAR activation can vary widely depending on receptor localization, temporal characteristics, and size of the signal (Bito et al., 1996; Fields et al., 1997; Hardingham et al., 1999; Chawla and Bading, 2001; Hardingham et al., 2001a, b). The focus of this study is the physiological role of extrasynaptic vs. synaptic NMDARs. Cultured neuron studies have suggested that NMDARs can exist as synaptic NR1/NR2A heteromers and extrasynaptic NR1/NR2B heteromers. These two receptor types may be coupled to very different cellular processes, with calcium entry through extrasynaptic NMDARs activating cell death mechanisms and LTD rather than LTP (Lu et al., 2001; Hardingham et al., 2002). Although these experiments have provided valuable clues about possible spatial and functional segregation of extrasynaptic NMDARs in neurons, the existence and physiological relevance of these receptors in intact tissue remains unclear. Our preliminary results, which are significantly different from culture measurements, suggest that approximately 40% of the NMDAR population is extrasynaptic in acute hippocampal slice dendrites. This indicates that there is a large pool of extrasynaptic receptors available for activation during periods of high presynaptic activity. Our underlying hypothesis is that extrasynaptic NMDARs participate in neuronal interactions under pathological and physiologically relevant conditions. This hypothesis will be tested by determining the size of the extrasynaptic NMDAR pool, subunit composition, and developmental expression in acute hippocampal brain slices. We will determine the conditions under which extrasynaptic receptors can participate in transmission and their role in the expression of long-term potentiation or depression.
描述(由申请人提供):N-甲基-D-天冬氨酸受体(NMDAR)激活可以导致长期和短期可塑性,促进细胞存活,启动细胞死亡,并且对于发育过程中正常的突触发生也至关重要。许多研究表明,NMDAR激活的后果可能会因受体的定位,时间特征和信号的大小而变化(Bito等,1996; Fields等,1997; Hardingham等,1999; Chawla and Bading; Chawla and Bading,2001; Hardingham et al。,2001a,b)。这项研究的重点是突触外与突触NMDAR的生理作用。培养的神经元研究表明,NMDAR可以作为突触NR1/NR2A杂体和外肌外NR1/NR2B异源物存在。这两种受体类型可以耦合到非常不同的细胞过程,钙通过外突激活细胞死亡机制和LTD而不是LTP的钙进入(Lu等,2001; Hardingham等,2002)。尽管这些实验提供了有关神经元外NMDAR的空间和功能分离的宝贵线索,但这些受体在完整的组织中的存在和生理相关性仍然不清楚。我们的初步结果与培养测量显着不同,这表明大约40%的NMDAR种群在急性海马切片树突中是外突触。这表明在高突触前活性期间,有大量的外突触受体可用于激活。我们的基本假设是,在病理和生理上相关的情况下,外鼻外NMDAR参与神经元相互作用。该假设将通过确定急性海马脑切片中的鼻鼻池,亚基组成和发育表达的大小来检验。我们将确定外交受体可以参与传播及其在长期增强或抑郁表达中的作用的条件。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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DIANA Leslie PETTIT其他文献
DIANA Leslie PETTIT的其他文献
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{{ truncateString('DIANA Leslie PETTIT', 18)}}的其他基金
The Physiology of Extra Synaptic NMDA Receptors
突触外 NMDA 受体的生理学
- 批准号:
7047251 - 财政年份:2006
- 资助金额:
$ 21.76万 - 项目类别:
MICROMAPPING OF LEAD INDUCED CHANGES TO NMDA RECEPTORS
铅引起的 NMDA 受体变化的微图谱
- 批准号:
6658035 - 财政年份:2001
- 资助金额:
$ 21.76万 - 项目类别:
MICROMAPPING OF LEAD INDUCED CHANGES TO NMDA RECEPTORS
铅引起的 NMDA 受体变化的微图谱
- 批准号:
6132592 - 财政年份:2001
- 资助金额:
$ 21.76万 - 项目类别:
MICROMAPPING OF LEAD INDUCED CHANGES TO NMDA RECEPTORS
铅引起的 NMDA 受体变化的微图谱
- 批准号:
6524699 - 财政年份:2001
- 资助金额:
$ 21.76万 - 项目类别:
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