Analysis of a Computational Model of Dopamine Synthesis and Release through Perturbation

Maell Cullen, KongFatt Wong-Lin

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Citations (Scopus)

Abstract

Dopamine is an important neurotransmitter responsible for regulating various brain functions such as learning and cognition. Dysfunctions within the dopaminergic system are implicated in many neurological and neuropsychiatric disorders. To understand such a complex system, biologically realistic multiscale computational models are necessary. Such models require the extraction of relevant and important factors or processes from one scale to bridge and interact with systems at other scales. In this paper, we analyze an influential computational model of dopamine synthesis and release within a pre-synaptic terminal by systematically perturbing its variables/substrates. Based on the relative changes in steady states and the time to reach the new perturbed steady states, we found that the substrates within the cascade of intracellular biochemical reactions can vary widely in terms of influence and timescale. We then categorize the substrates according to their relative timescales and changes in steady states. The perturbation results are then used to guide our selection for the most appropriate equations and functions to be approximated in developing reduced models of the original model. Our preliminary simulation results show that either a slow or fast version of the reduced model can be simulated significantly faster than the original model. Our work demonstrates, through perturbation analysis, the feasibility of reduced models of the dopaminergic presynaptic terminal to improve computational efficiency, implement in multiscale modelling, and in silico neuropharmacology.

Workshop

WorkshopIEEE International Conference on Bioinformatics and Biomedicine (BIBM), Empowering Systems Medicine Through Optimal Computational Modelling Workshop
Period1/01/14 → …

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Substrates
Dopamine
Computational efficiency
Large scale systems
Brain

Cite this

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title = "Analysis of a Computational Model of Dopamine Synthesis and Release through Perturbation",
abstract = "Dopamine is an important neurotransmitter responsible for regulating various brain functions such as learning and cognition. Dysfunctions within the dopaminergic system are implicated in many neurological and neuropsychiatric disorders. To understand such a complex system, biologically realistic multiscale computational models are necessary. Such models require the extraction of relevant and important factors or processes from one scale to bridge and interact with systems at other scales. In this paper, we analyze an influential computational model of dopamine synthesis and release within a pre-synaptic terminal by systematically perturbing its variables/substrates. Based on the relative changes in steady states and the time to reach the new perturbed steady states, we found that the substrates within the cascade of intracellular biochemical reactions can vary widely in terms of influence and timescale. We then categorize the substrates according to their relative timescales and changes in steady states. The perturbation results are then used to guide our selection for the most appropriate equations and functions to be approximated in developing reduced models of the original model. Our preliminary simulation results show that either a slow or fast version of the reduced model can be simulated significantly faster than the original model. Our work demonstrates, through perturbation analysis, the feasibility of reduced models of the dopaminergic presynaptic terminal to improve computational efficiency, implement in multiscale modelling, and in silico neuropharmacology.",
author = "Maell Cullen and KongFatt Wong-Lin",
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doi = "10.1109/BIBM.2014.6999252",
language = "English",
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Cullen, M & Wong-Lin, K 2014, Analysis of a Computational Model of Dopamine Synthesis and Release through Perturbation. in Unknown Host Publication. IEEE International Conference on Bioinformatics and Biomedicine (BIBM), Empowering Systems Medicine Through Optimal Computational Modelling Workshop, 1/01/14. https://doi.org/10.1109/BIBM.2014.6999252

Analysis of a Computational Model of Dopamine Synthesis and Release through Perturbation. / Cullen, Maell; Wong-Lin, KongFatt.

Unknown Host Publication. 2014.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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AU - Wong-Lin, KongFatt

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N2 - Dopamine is an important neurotransmitter responsible for regulating various brain functions such as learning and cognition. Dysfunctions within the dopaminergic system are implicated in many neurological and neuropsychiatric disorders. To understand such a complex system, biologically realistic multiscale computational models are necessary. Such models require the extraction of relevant and important factors or processes from one scale to bridge and interact with systems at other scales. In this paper, we analyze an influential computational model of dopamine synthesis and release within a pre-synaptic terminal by systematically perturbing its variables/substrates. Based on the relative changes in steady states and the time to reach the new perturbed steady states, we found that the substrates within the cascade of intracellular biochemical reactions can vary widely in terms of influence and timescale. We then categorize the substrates according to their relative timescales and changes in steady states. The perturbation results are then used to guide our selection for the most appropriate equations and functions to be approximated in developing reduced models of the original model. Our preliminary simulation results show that either a slow or fast version of the reduced model can be simulated significantly faster than the original model. Our work demonstrates, through perturbation analysis, the feasibility of reduced models of the dopaminergic presynaptic terminal to improve computational efficiency, implement in multiscale modelling, and in silico neuropharmacology.

AB - Dopamine is an important neurotransmitter responsible for regulating various brain functions such as learning and cognition. Dysfunctions within the dopaminergic system are implicated in many neurological and neuropsychiatric disorders. To understand such a complex system, biologically realistic multiscale computational models are necessary. Such models require the extraction of relevant and important factors or processes from one scale to bridge and interact with systems at other scales. In this paper, we analyze an influential computational model of dopamine synthesis and release within a pre-synaptic terminal by systematically perturbing its variables/substrates. Based on the relative changes in steady states and the time to reach the new perturbed steady states, we found that the substrates within the cascade of intracellular biochemical reactions can vary widely in terms of influence and timescale. We then categorize the substrates according to their relative timescales and changes in steady states. The perturbation results are then used to guide our selection for the most appropriate equations and functions to be approximated in developing reduced models of the original model. Our preliminary simulation results show that either a slow or fast version of the reduced model can be simulated significantly faster than the original model. Our work demonstrates, through perturbation analysis, the feasibility of reduced models of the dopaminergic presynaptic terminal to improve computational efficiency, implement in multiscale modelling, and in silico neuropharmacology.

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