@article{18329,
  author = {Mar{\'\i}a Mesa and Guadalupe Garcia and Fred Hoerndli and Kimberly McCabe and Padmini Rangamani},
  title = {Spine apparatus modulates Ca2+ in spines through spatial localization of sources and sinks},
  abstract = {Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, IP3R localization, spine membrane geometry and SER geometry can impact Ca2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on its location in the SER and on the SER geometry. To maximize Ca2+ in the dendrites (for activating clusters of spines and spine-to-spine communication), a laminar SA was favourable with RyRs localized in the neck region, closer to the dendrite. Furthermore locating the IP3Rs in the dendrite, as measured experimentally, also increases Ca2+ in the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca2+ dynamics differently from spines without ER through a combination of geometry and receptor localization.},
  year = {2025},
  journal = {Journal Of Physiology},
  volume = {603},
  pages = {4785-4816},
  publisher = {Wiley},
  doi = {https://doi.org/10.1101/2023.09.22.558941},
}