NDLI: Integrated dopaminergic neuronal model with reduced intracellular processes and inhibitory autoreceptors

Content Provider	IET Digital Library
Author	Cullen, Maell Lin, Kong Fatt Wong
Abstract	Dopamine (DA) is an important neurotransmitter for multiple brain functions, and dysfunctions of the dopaminergic system are implicated in neurological and neuropsychiatric disorders. Although the dopaminergic system has been studied at multiple levels, an integrated and efficient computational model that bridges from molecular to neuronal circuit level is still lacking. In this study, the authors aim to develop a realistic yet efficient computational model of a dopaminergic pre-synaptic terminal. They first systematically perturb the variables/substrates of an established computational model of DA synthesis, release and uptake, and based on their relative dynamical timescales and steady-state changes, approximate and reduce the model into two versions: one for simulating hourly timescale, and another for millisecond timescale. They show that the original and reduced models exhibit rather similar steady and perturbed states, whereas the reduced models are more computationally efficient and illuminate the underlying key mechanisms. They then incorporate the reduced fast model into a spiking neuronal model that can realistically simulate the spiking behaviour of dopaminergic neurons. In addition, they successfully include autoreceptor-mediated inhibitory current explicitly in the neuronal model. This integrated computational model provides the first step toward an efficient computational platform for realistic multiscale simulation of dopaminergic systems in in silico neuropharmacology.
Starting Page	245
Ending Page	258
Page Count	14
ISSN	17518849
Volume Number	9
e-ISSN	17518857
Issue Number	Issue 6, Dec (2015)
Alternate Webpage(s)	https://digital-library.theiet.org/content/journals/iet-syb/9/6
Alternate Webpage(s)	https://digital-library.theiet.org/content/journals/10.1049/iet-syb.2015.0018
Journal	IET Systems Biology
Publisher Date	2015-12-01
Access Restriction	Open
Rights Holder	© The Institution of Engineering and Technology
Subject Keyword	Autoreceptor-mediated Inhibitory Current Biomedical Engineering Biomedical Measurement And Imaging Biophysics of Neurophysiological Processes Brain Computational Model Dopaminergic Presynaptic Terminal Dysfunctions Efficient Computational Platform In Silico Neuropharmacology Inhibitory Autoreceptors Integrated Computational Model Integrated Dopaminergic Neuronal Model Medical Disorders Molecular Level Multiple Brain Function Neurological Disorders Neuronal-circuit Level Neurophysiology Neuropsychiatric Disorders Neurotransmitter Organic Compound Realistic Multiscale Simulation Reduced Fast Model Reduced Intracellular Processes Relative Dynamical Timescales Spiking Neuronal Model Steady Perturbed State
Content Type	Text
Resource Type	Article
Subject	Cell Biology Genetics Molecular Biology Modeling and Simulation Biotechnology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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