Rate-limiting recovery processes in neurotransmission under sustained stimulation
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Rate-limiting recovery processes in neurotransmission under sustained stimulation. / Ernst, Ariane; Unger, Nathalie; Schütte, Christof; Walter, Alexander M.; Winkelmann, Stefanie.
In: Mathematical Biosciences, Vol. 362, 109023, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rate-limiting recovery processes in neurotransmission under sustained stimulation
AU - Ernst, Ariane
AU - Unger, Nathalie
AU - Schütte, Christof
AU - Walter, Alexander M.
AU - Winkelmann, Stefanie
N1 - Publisher Copyright: © 2023 Elsevier Inc.
PY - 2023
Y1 - 2023
N2 - At active zones of chemical synapses, an arriving electric signal induces the fusion of vesicles with the presynaptic membrane, thereby releasing neurotransmitters into the synaptic cleft. After a fusion event, both the release site and the vesicle undergo a recovery process before becoming available for reuse again. Of central interest is the question which of the two restoration steps acts as the limiting factor during neurotransmission under high-frequency sustained stimulation. In order to investigate this problem, we introduce a non-linear reaction network which involves explicit recovery steps for both the vesicles and the release sites, and includes the induced time-dependent output current. The associated reaction dynamics are formulated by means of ordinary differential equations (ODEs), as well as via the associated stochastic jump process. While the stochastic jump model describes the dynamics at a single active zone, the average over many active zones is close to the ODE solution and shares its periodic structure. The reason for this can be traced back to the insight that recovery dynamics of vesicles and release sites are statistically almost independent. A sensitivity analysis on the recovery rates based on the ODE formulation reveals that neither the vesicle nor the release site recovery step can be identified as the essential rate-limiting step but that the rate-limiting feature changes over the course of stimulation. Under sustained stimulation, the dynamics given by the ODEs exhibit transient changes leading from an initial depression of the postsynaptic response to an asymptotic periodic orbit, while the individual trajectories of the stochastic jump model lack the oscillatory behavior and asymptotic periodicity of the ODE-solution.
AB - At active zones of chemical synapses, an arriving electric signal induces the fusion of vesicles with the presynaptic membrane, thereby releasing neurotransmitters into the synaptic cleft. After a fusion event, both the release site and the vesicle undergo a recovery process before becoming available for reuse again. Of central interest is the question which of the two restoration steps acts as the limiting factor during neurotransmission under high-frequency sustained stimulation. In order to investigate this problem, we introduce a non-linear reaction network which involves explicit recovery steps for both the vesicles and the release sites, and includes the induced time-dependent output current. The associated reaction dynamics are formulated by means of ordinary differential equations (ODEs), as well as via the associated stochastic jump process. While the stochastic jump model describes the dynamics at a single active zone, the average over many active zones is close to the ODE solution and shares its periodic structure. The reason for this can be traced back to the insight that recovery dynamics of vesicles and release sites are statistically almost independent. A sensitivity analysis on the recovery rates based on the ODE formulation reveals that neither the vesicle nor the release site recovery step can be identified as the essential rate-limiting step but that the rate-limiting feature changes over the course of stimulation. Under sustained stimulation, the dynamics given by the ODEs exhibit transient changes leading from an initial depression of the postsynaptic response to an asymptotic periodic orbit, while the individual trajectories of the stochastic jump model lack the oscillatory behavior and asymptotic periodicity of the ODE-solution.
KW - Neurotransmission models
KW - Nonlinear reaction networks
KW - Sustained stimulation
KW - Vesicle fusion dynamics
U2 - 10.1016/j.mbs.2023.109023
DO - 10.1016/j.mbs.2023.109023
M3 - Journal article
C2 - 37245846
AN - SCOPUS:85161648975
VL - 362
JO - Mathematical Biosciences
JF - Mathematical Biosciences
SN - 0025-5564
M1 - 109023
ER -
ID: 357473817