TY - JOUR

T1 - Influence of T-Bar on Calcium Concentration Impacting Release Probability

AU - Knodel, Markus M

AU - Dutta Roy, Ranjita

AU - Wittum, Gabriel

N1 - KAUST Repository Item: Exported on 2022-05-23
Acknowledgements: MK thanks Anton Vadimovich Chizhov of the Ioffe Institute (Russian Academy of Sciences), Sankt Petersburg, Russian Federation, for providing data for validation of the implementation of the VGCC calcium influx model, for various other stimulating discussions on the subject, for very helpful hints concerning literature study, data evaluation, and writing of this paper as well as for his very kind proof reading the paper. Further, MK thanks Sebastian Reiter (GCSC Frankfurt) for his kind support in the development of the geometric setup and meshing of the computational grid, Michael Heisig (GCSC Frankfurt) for his very kind proof reading of the manuscript, and the High-Performance Computing Center Stuttgart (HLRS) for the supplied computing time at the Apollo Hawk supercomputer, where the computations of this project were performed. The authors wish to express their sincere thanks to the Referees for their thorough and critical reviews of our work. This work has been supported by the German Ministry of Economics and Technology (BMWi) in the project HYMNE (02E11809B).

PY - 2022/5/2

Y1 - 2022/5/2

N2 - The relation of form and function, namely the impact of the synaptic anatomy on calcium dynamics in the presynaptic bouton, is a major challenge of present (computational) neuroscience at a cellular level. The Drosophila larval neuromuscular junction (NMJ) is a simple model system, which allows studying basic effects in a rather simple way. This synapse harbors several special structures. In particular, in opposite to standard vertebrate synapses, the presynaptic boutons are rather large, and they have several presynaptic zones. In these zones, different types of anatomical structures are present. Some of the zones bear a so-called T-bar, a particular anatomical structure. The geometric form of the T-bar resembles the shape of the letter "T" or a table with one leg. When an action potential arises, calcium influx is triggered. The probability of vesicle docking and neurotransmitter release is superlinearly proportional to the concentration of calcium close to the vesicular release site. It is tempting to assume that the T-bar causes some sort of calcium accumulation and hence triggers a higher release probability and thus enhances neurotransmitter exocytosis. In order to study this influence in a quantitative manner, we constructed a typical T-bar geometry and compared the calcium concentration close to the active zones (AZs). We compared the case of synapses with and without T-bars. Indeed, we found a substantial influence of the T-bar structure on the presynaptic calcium concentrations close to the AZs, indicating that this anatomical structure increases vesicle release probability. Therefore, our study reveals how the T-bar zone implies a strong relation between form and function. Our study answers the question of experimental studies (namely "Wichmann and Sigrist, Journal of neurogenetics 2010") concerning the sense of the anatomical structure of the T-bar.

AB - The relation of form and function, namely the impact of the synaptic anatomy on calcium dynamics in the presynaptic bouton, is a major challenge of present (computational) neuroscience at a cellular level. The Drosophila larval neuromuscular junction (NMJ) is a simple model system, which allows studying basic effects in a rather simple way. This synapse harbors several special structures. In particular, in opposite to standard vertebrate synapses, the presynaptic boutons are rather large, and they have several presynaptic zones. In these zones, different types of anatomical structures are present. Some of the zones bear a so-called T-bar, a particular anatomical structure. The geometric form of the T-bar resembles the shape of the letter "T" or a table with one leg. When an action potential arises, calcium influx is triggered. The probability of vesicle docking and neurotransmitter release is superlinearly proportional to the concentration of calcium close to the vesicular release site. It is tempting to assume that the T-bar causes some sort of calcium accumulation and hence triggers a higher release probability and thus enhances neurotransmitter exocytosis. In order to study this influence in a quantitative manner, we constructed a typical T-bar geometry and compared the calcium concentration close to the active zones (AZs). We compared the case of synapses with and without T-bars. Indeed, we found a substantial influence of the T-bar structure on the presynaptic calcium concentrations close to the AZs, indicating that this anatomical structure increases vesicle release probability. Therefore, our study reveals how the T-bar zone implies a strong relation between form and function. Our study answers the question of experimental studies (namely "Wichmann and Sigrist, Journal of neurogenetics 2010") concerning the sense of the anatomical structure of the T-bar.

UR - http://hdl.handle.net/10754/678135

UR - https://www.frontiersin.org/articles/10.3389/fncom.2022.855746/full

U2 - 10.3389/fncom.2022.855746

DO - 10.3389/fncom.2022.855746

M3 - Article

C2 - 35586479

VL - 16

JO - Frontiers in Computational Neuroscience

JF - Frontiers in Computational Neuroscience

SN - 1662-5188

ER -