Biology subjects

Bartol, T.

Publications and source records attributed to Bartol, T..

3 recordsLinked to original sources

bioRxiv2025

Synaptic Spine Head Morphodynamics from Graph Grammar Rules for Actin Dynamics

There is a morphodynamic component to synaptic learning by which changes in dendritic (postsynaptic) spine head size are associated with the strengthening or weakening of the synaptic connection between two neurons. The membrane shape and size dynamics is sculpted by the growth dynamics of the enclosed actin cytoskeleton. We use Dynamical Graph Grammars (DGGs) governing dynamic labelled graphs embedded in two dimensions to model networks of actin filaments and the enclosing membrane in spine head morphology. We demonstrate the flexibility and extensibility of the framework by encoding detailed biophysical as well as biochemical models, obeying constraints of invariance and conservation, in DGG rule sets. From graph-local energy functions for cytoskeleton actin interacting and membrane, we specialize dissipative stochastic dynamics to an exhaustive collection of graph-local neighborhood types for the rule left hand sides. Extensively simulating the resulting model delineates effects of four actin-binding proteins, and their epistatic relationships, on morphology.

biophysics↗

bioRxiv2018

Presynaptic Endoplasmic Reticulum Contributes Crucially to Short-term Plasticity in Small Hippocampal Synapses

Short-term plasticity (STP) of the presynaptic terminal maintains a brief history of activity experienced by the synapse that may otherwise remain unseen by the postsynaptic neuron. These synaptic changes are primarily regulated by calcium dynamics in the presynaptic terminal. A rapid increase in intracellular calcium is initiated by the opening of voltage-dependent calcium channels in response to depolarization, the main source of calcium required for vesicle fusion. Separately, electron-microscopic studies of hippocampal CA3-CA1 synapses reveal the strong presence of endoplasmic reticulum (ER) in all presynaptic terminals. However, the precise role of the ER in modifying STP at the presynaptic terminal remains unexplored. To investigate the contribution of ER in modulating calcium dynamics in small hippocampal boutons, we performed in silico experiments in a physiologically-realistic canonical synaptic geometry based on reconstructions of CA3-CA1 Schaffer collaterals in the rat hippocampus. The model predicts that presynaptic calcium stores are critical in generating the observed paired-pulse ratio (PPR) of normal CA3-CA1 synapses. In control synapses with intact ER, SERCA pumps act as additional calcium buffers, lowering the intrinsic release probability of vesicle release and increasing PPR. In addition, the presence of ER allows ongoing activity to trigger calcium influx from the presynaptic ER via ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs). Intracellular stores and their associated machinery also allows a synapse with a low release probability to operate more reliably due to attenuation of calcium fluctuations. Finally, blocking ER activity in the presynaptic terminal mimics the pathological state of a low facilitating synapse characterized in animal models of Alzheimers disease, and underscores the critical role played by presynaptic stores in normal function.

neuroscience↗

bioRxiv2018

Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium

Dendritic spines are small subcompartments that protrude from the dendrites of neurons and 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 specific nature of these shape-function relationships 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, a specialized endoplasmic reticulum compartment in the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multi-compartment reaction-diffusion model of calcium dynamics in three dimensions 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 make several important predictions - first, the volume-to-surface area ratio of the spine regulates calcium dynamics, second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion, and finally the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines.

systems biology↗