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Multiscale modeling of presynaptic dynamics from molecular to mesoscale
Jonathan W Garcia1,2, Thomas M Bartol2, Terrence J Sejnowski1,2
1Division of Biological Sciences, University of California San Diego, La Jolla, California, United States of America.
Plos Computational Biology
|May 9, 2022
Summary
This study models neurotransmitter release dynamics at chemical synapses by analyzing calcium (Ca2+) influx. It reveals how release probability and timing depend on Ca2+ proximity, crucial for understanding neural information processing.
Area of Science:
- Neuroscience
- Computational Biology
- Biophysics
Background:
- Synaptic transmission efficacy relies on activity-dependent calcium (Ca2+) influx and accumulation.
- Modeling these complex processes requires computationally efficient frameworks for accurate phenomenology.
Purpose of the Study:
- To develop a computationally efficient model for neurotransmitter release dynamics.
- To characterize the timing and probability of neurotransmitter release with high resolution.
Main Methods:
- Utilized MCell models of hippocampal axons to obtain Ca2+ concentration traces.
- Employed deterministic state vector models of synaptotagmin 1 and 7 (Syt-1/7) driven by Ca2+ traces.
- Applied functional fits to high-resolution instantaneous release rate profiles.
Main Results:
- Synchronous release occurred within 0.5 microns of Ca2+ influx; asynchronous release was consistent at all distances.
- Both fast and slow release mechanisms showed multi-exponential release rate curves.
- Release magnitudes decayed exponentially with distance from the Ca2+ source.
Conclusions:
- Functional descriptions of vesicular release dynamics were derived.
- These findings provide a foundation for efficient mesoscale modeling of synaptic transmission.
- Understanding release dynamics is key for modeling neural circuits and disease states.
