The Function of Ca2+ Waves In Hippocampal Neurons.

海马神经元中 Ca2 波的功能。

• 批准号: 6825766
• 负责人: Mark F Yeckel
• 金额: $ 31.68万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825766
• 关键词: calcium channel; calcium flux; calcium ion; charge coupled device camera; dendrites; genetically modified animals; glutamate receptor; hippocampus; laboratory mouse; laboratory rat; ligands; long term potentiation; mossy fiber; neural information processing; neural plasticity; neurons; perfusion; pyramidal cells; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): Several cellular factors--with profoundly different spatial and temporal properties--contribute to the ability of dendrites to integrate and shape synaptic responses in neurons. The primary goal of this project will be to investigate how Ca2+ release from intracellular stores in hippocampal CA1 and CA3 pyramidal neurons contributes to dendritic function. To accomplish this goal we will use whole-cell patch-clamp recording and high-speed fluorescence imaging in slices from adult (>6 weeks old) mice and rats. The underlying theme is that internal Ca2+ release, and consequent propagation of intracellular Ca2+ waves, is not only capable of contributing to synaptic plasticity such that occurs with long-term potentiation (LTP) and long-term depression (LTD), but also provides a temporally unique and biochemically robust means for communication within individual neurons. In addition to investigating internal Ca2+ release, we propose to examine whether Ca2+ release modulates ion-gated and ligand-gated channels, and how this modulation affects dendritic function and synaptic integration. More specifically, our first aim will be to continue studies characterizing the basic properties of synaptically evoked internal Ca2+ release in hippocampal neurons under physiologically realistic conditions. We will also test the hypothesis that kainate receptor-activation can lead to internal Ca2+ release via metabotropic receptor activation. In the second aim we will investigate the hypothesis that an increase in InsP3 at hippocampal mossy fiber synapses, and consequent internal Ca2+ release, is capable of inducing long-term changes in synaptic strength such that occurs with LTP and LTD. In the third aim we will examine whether internal Ca2+ release and Ca2+ waves can modulate backpropagating action potentials and ligand-gated channels, and if so, determine how this modulation contributes to dendritic function and synaptic integration, particularly as it relates to modifying input from convergent subsets of synapses on pyramidal neurons. More generally, the results of these experiments will provide essential information concerning the functional properties of hippocampal pyramidal neurons, and will also clarify at a more global level the cellular mechanisms underlying information processing by single neurons in the hippocampus.

描述（由申请人提供）：几个细胞因素 - 与截然不同的空间和时间特性，与树突在神经元中整合和形成突触反应的能力相吻合。该项目的主要目标是研究海马CA1和CA3锥体神经元中细胞内存储中的Ca2+如何促进树突功能。为了实现这一目标，我们将在成年（> 6周）的小鼠和大鼠的切片中使用全细胞贴片钳记录和高速荧光成像。潜在的主题是内部Ca2+释放以及随之而来的细胞内Ca2+波的传播不仅能够有助于突触可塑性，因此长期增强（LTP）和长期抑郁症（LTD）（LTD）也能够在单个神经元内提供时间独特和生物学上强大的交流手段。除了研究内部Ca2+释放外，我们还建议检查Ca2+释放是否调节离子门控和配体门控通道，以及该调节如何影响树突功能和突触整合。更具体地说，我们的第一个目的是继续研究，以在生理上现实的条件下在海马神经元中突触诱发的内部Ca2+释放的基本特性。我们还将检验以下假设：海藻酸盐受体激活可以通过代谢受体激活导致内部Ca2+释放。在第二个目标中，我们将研究以下假设：海马苔藓纤维突触中的INSP3增加以及随之而来的内部Ca2+释放能够诱导LTP和LTD发生的突触强度的长期变化。在第三个目的中，我们将检查内部CA2+释放和Ca2+波是否可以调节反向传播的动作电位和配体门控通道，如果是的，请确定该调节如何有助于树突的功能和突触整合，尤其是与在Pyramidal神经元上的融合亚基中修改输入相关的情况。更普遍地，这些实验的结果将提供有关海马锥体神经元功能特性的基本信息，并且还将在更全球的水平上阐明海马中单个神经元的细胞机制。