Action potential-evoked Ca2+ signals in CA1 pyramidal cell presynaptic terminals (Hamid et al 2019)

The attached file contains models for 4 different MCell simulations of the same presynaptic terminal model. Calbindin22_40uM_files - model of Ca entry, buffering and extrusion from a single varicosity of a CA1 pyramidal neuron axon containing 40 µM simulated calbindin28K (binding constants from Nagerl et al 2000, Biophys J 79:3009–3018. doi:10.1016/S0006-3495(00)76537-4 pmid:11106608. This model represents calbindin28K with 2 low and 2 intermediate affinity Ca2+ binding sites. Calbindin31_40uM_files - similar to above but with calbindin28K with 1 low and 3 intermediate affinity Ca2+ binding sites. Calmodulin_40uM_files - model of Ca2+ using calmodulin and the principle buffer, again at 40 µM (from Faas et al 2011, Nat Neurosci 14:301–304. doi:10.1038/nn.2746 pmid:21258328. Paired_Pulses - model used to simulate paired pulses of Ca2+ entry to these presynaptic terminals These models were based on experimentally quantified action potential-evoked Calcium entry to presynaptic varicosities of CA1 pyramidal neurons. How Ca enters, diffuses, is buffered and is pumped out of the cytosol was first determined. The study used Calcium-sensitive dyes of different affinities over a range of concentrations to buffer Calcium. Following this quantification we used these data to construct Monte Carlo simulations of the Calcium transients to determine dynamics of the Calcium signal at spatiotemporal resolutions not possible with imaging methods. From these simulations we have demonstrated very high concentrations, short duration Calcium transients that are dominated by Calcium diffusion within tens of nanometers of Calcium channels. We have quantified channel densities, constrained buffer identities and determined properties of presynaptic Calcium during trains of action potentials. This published work can be found at: Edaeni Hamid, Emily Church and Simon Alford Quantitation and Simulation of Single Action Potential-Evoked Ca2+ Signals in CA1 Pyramidal Neuron Presynaptic Terminals eNeuro 24 September 2019, 6 (5) ENEURO.0343-19.2019; DOI:

Model Type: Synapse

Cell Type(s): Hippocampus CA1 pyramidal GLU cell

Model Concept(s): Reaction-diffusion; Synaptic Plasticity; Action Potentials

Simulation Environment: MCell


Hamid E, Church E, Alford S. (2019). Quantitation and Simulation of Single Action Potential-Evoked Ca2+ Signals in CA1 Pyramidal Neuron Presynaptic Terminals. eNeuro. 6 [PubMed]

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