Spine apparatus modulates Ca ²⁺ in spines through spatial localization of sources and sinks

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 Ca 2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca 2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca 2+ in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to 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 Ca 2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca 2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. 1 Highlights RyR opening in dendritic spine ER is location dependent and spine geometry dependent. Ca 2+ buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated. RyRs located towards the ER neck allow for more Ca 2+ to reach the dendrites. RyRs located towards the spine head are favorable for increased Ca 2+ in spines. Figure 1: Graphical abstract. Factors governing the dynamics of Ca 2+ in dendritic spines include plasma membrane geometry, RyR distribution and ER laminarity.