Goethe Center for Scientific Computing, Computational Neuroscience, Goethe University Frankfurt, Frankfurt, Germany.
Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, 79104, Germany.
Sci Rep. 2018 Oct 23;8(1):15624. doi: 10.1038/s41598-018-33343-9.
The endoplasmic reticulum (ER) forms a complex endomembrane network that reaches into the cellular compartments of a neuron, including dendritic spines. Recent work discloses that the spine ER is a dynamic structure that enters and leaves spines. While evidence exists that ER Ca release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca signaling. Our simulations, which account for Ca exchange on the plasma membrane and ER, show that spine ER needs to be present in distinct morphological conformations in order to overcome a barrier between the spine and dendritic shaft. We demonstrate that RyR-carrying spine ER promotes spine-to-dendrite Ca signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca communication, while maintaining aspects of Ca homeostasis in the spine head. Our work emphasizes the relevance of precise positioning of RyR-containing spine ER in regulating the strength and timing of spine Ca signaling, which could play an important role in tuning spine-to-dendrite Ca communication and homeostasis.
内质网（ER）形成了一个复杂的内膜网络，延伸到神经元的细胞隔室，包括树突棘。最近的工作揭示了棘突 ER 是一个动态的结构，可以进入和离开棘突。虽然有证据表明 ER Ca 释放参与了突触可塑性，但棘突 ER 形态的作用仍然未知。我们结合了一个新的 3D 棘突生成器和 3D Ca 建模，解决了 ER 定位对棘突到树突 Ca 信号的相关性问题。我们的模拟考虑了质膜和 ER 上的 Ca 交换，表明为了克服棘突和树突干之间的障碍，棘突 ER 需要以不同的形态构象存在。我们证明了携带 RyR 的棘突 ER 以位置依赖的方式促进了棘突到树突的 Ca 信号。我们的模拟表明，携带 RyR 的 ER 可以根据棘突 ER 的精确位置引发时间延迟的 Ca 回响。随着棘突的生长，ER 的结构重组恢复了棘突到树突的 Ca 通讯，同时保持了棘突头部的 Ca 稳态的某些方面。我们的工作强调了 RyR 携带的棘突 ER 的精确定位在调节棘突 Ca 信号的强度和时间方面的相关性，这可能在调节棘突到树突的 Ca 通讯和稳态方面发挥重要作用。
