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

ABSTRACT: 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 Ca²⁺ release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca²⁺ modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca²⁺ signaling. Our simulations, which account for Ca²⁺ 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 Ca²⁺ signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca²⁺ reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca²⁺ communication, while maintaining aspects of Ca²⁺ 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 Ca²⁺ signaling, which could play an important role in tuning spine-to-dendrite Ca²⁺ communication and homeostasis.

SUBMITTER: Breit M 

PROVIDER: S-EPMC6199256 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature