Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum

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(2+) release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca(2+) modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca(2+) signaling. Our simulations, which account for Ca(2+) 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(2+) signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca(2+) reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca(2+) communication, while maintaining aspects of Ca(2+) 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(2+) signaling, which could play an important role in tuning spine-to-dendrite Ca(2+) communication and homeostasis.