Calcium Signals in Neurons During Early Development: Experiments and Theory

神经元早期发育过程中的钙信号：实验和理论

• 批准号: 327008147
• 负责人: Privatdozent Dr. Friedrich Johenning
• 金额: --
• 依托单位: Institut für Physik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/327008147?language=en
• 关键词: Calcium; Signals; Neurons; During; Early

Calcium is a key player in neuronal signaling, since it can serve both as electrical charge carrier at the membrane and biochemical second messenger. In this project we aim at its role in neuronal circuit formation during early postnatal brain development, which is characterized by the generation and elimination of dendrites, spines, and synapses. Neuronal plasticity and circuit formation have been shown to depend on cytoplasmic calcium elevations, which are necessary for dendritic and filopodial outgrowth as well as spine formation. We recently demonstrated that calcium release from intracellular stores via ryanodine receptors is able to generate signaling nanodomains involved in plasticity of dendritic spines (Johenning et al., PlosBiology, 2015).We propose to investigate the functional interaction between calcium signals and spine formation in an interdisciplinary experimental and theoretical approach. The dynamics of calcium is a phenomenon highly variable in space and time. Cytosolic calcium levels are modified by influx from the plasma membrane and the coordinated release from intracellular stores through receptor channels. Once calcium is released it diffuses into the cytosol and increases the open probability of neighboring intracellular calcium channels. This provides a self-amplifying mechanism, which is crucial for the generation of calcium waves.Using advanced experimental techniques we will characterize the distribution of calcium sources with a focus on intracellular stores in dendrites and the contributing factors for calcium signals. Theoretical research will then be based on the experimental results to propose and study a quantitative model of calcium waves in dendrites and spines. The theoretical methods, specifically adapted to the multi-scale nature of calcium concentration, allow a detailed investigation of the local distribution of calcium in micro- and nanodomains, which is not accessible by fluorescence microscopy. Our interdisciplinary approach will further identify the spatial patterning of calcium signals to the distribution of spines and branching pattern of dendrites. We aim at understanding how calcium signals govern the development of neonatal circuits.

钙是神经元信号传导的关键参与者，因为它既可以作为膜上的电荷载体，也可以作为生化第二信使。在这个项目中，我们的目标是在早期出生后的大脑发育，其特点是树突，棘和突触的产生和消除神经回路的形成中的作用。神经元的可塑性和回路的形成依赖于细胞质钙离子的升高，这对于树突和丝状伪足的生长以及棘的形成是必要的。我们最近证明，通过兰尼碱受体从细胞内储存释放的钙能够产生参与树突棘可塑性的信号传导纳米结构域（Johenning等人，PlosBiology，2015）。我们建议以跨学科的实验和理论方法研究钙信号和脊柱形成之间的功能相互作用。钙的动力学是一种在空间和时间上高度可变的现象。细胞溶质钙水平通过从质膜流入和通过受体通道从细胞内储存的协同释放而改变。一旦钙被释放，它扩散到胞质溶胶中并增加邻近细胞内钙通道的开放概率。这提供了一个自我放大的机制，这是至关重要的钙波的产生。使用先进的实验技术，我们将表征钙源的分布，专注于细胞内存储在树突和钙信号的贡献因素。理论研究将根据实验结果提出并研究树突和棘中钙波的定量模型。理论方法，特别是适应钙浓度的多尺度性质，允许详细调查钙在微区和纳米区的局部分布，这是荧光显微镜无法访问的。我们的跨学科方法将进一步确定钙信号的空间模式的分布的棘和树突的分支模式。 我们的目标是了解钙信号如何管理新生儿电路的发展。

项目成果

Circuit-Specific Dendritic Development in the Piriform Cortex

梨状皮层中电路特异性树突的发育

• DOI: 10.1523/eneuro.0083-20.2020
• 发表时间: 2020
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Moreno-Velasquez L;Lenzi S;Kaehne M;Breustedt J;Schmitz D;Rüdiger S;Johenning FW
• 通讯作者: Johenning FW