RT Journal Article
SR Electronic
T1 Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 386367
DO 10.1101/386367
A1 Miriam Bell
A1 Tom Bartol
A1 Terrence Sejnowski
A1 Padmini Rangamani
YR 2018
UL http://biorxiv.org/content/early/2018/08/07/386367.abstract
AB Dendritic spines are small subcompartments protruding from the dendrites of neurons that are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the nature of this shape-function relationship is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus in modulating rapid calcium dynamics using mathematical modelling. We developed a spatial multi-compartment reaction-diffusion model of calcium dynamics with various flux sources including N-methyl-D-aspartate receptors (NMDAR), voltage sensitive calcium channels (VSCC), and different ion pumps on the plasma membrane. Using this model, we have made several important predictions – i) size and shape of the spine regulate calcium dynamics, ii) membrane fluxes nonlinearly impact calcium dynamics both temporally and spatially, and iii) the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling calcium concentration. These predictions set the stage for future experimental investigations.Author summary Dendritic spines, small protrusions from dendrites in neurons, are a hotbed of chemical activity. Synaptic plasticity and signaling in the postsynaptic dendritic spine are closely dependent on the spatiotemporal dynamics of calcium within the spine. This complexity is further enhanced by the distinct shapes and sizes of spines associated with development and physiology. Even so, how spine size and internal organization affects calcium dynamics remains poorly understood. To elucidate the relationship between signaling and geometry, we developed a 3D spatiotemporal model of calcium dynamics in idealized geometries. We used this model to investigate the impact of dendritic spine size, shape, and membrane flux distribution on calcium dynamics. We found that the interaction between spine geometry and the membrane fluxes through various receptors and pumps plays an important role in governing the spatiotemporal dynamics of calcium. Since it is known that dendritic spine size and shape can also change in response to downstream dynamics following calcium influx, our investigation serves as a critical step towards developing a mechanistic framework to interrogate the feedback between signaling and geometry.