Spine apparatus modulates Ca²⁺ 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 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. KEY POINTS: Ca²⁺ transients in the spine are characterized by the interplay among membrane receptors, RyRs, SERCA, and IP₃Rs. Here we build a spatial, particle-based stochastic model that integrates these components to study how the spine apparatus and receptor localization affect Ca²⁺ signaling. Our results show that positioning RyRs near the neck of the spine apparatus enhances spine-to-dendrite communication. Additionally, our model highlights the importance of membrane curvature and spine apparatus shape for Ca²⁺ signaling within dendritic spines.