title: An integrated modelling framework for neural circuits with multiple neuromodulators.
abstract: Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies.
authors.affiliation: School of Computer Science, University of Manchester, Manchester, UK.
authors.forename: Alok
authors.identifier: 0000-0003-1259-4902
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Vahab
authors.identifier: 0000-0002-1892-5525
authors.initials: V
authors.lastname: Youssofzadeh
authors.affiliation: Computer Science and Engineering, Indian Institute of Technology (IIT) Jodhpur, Jodhpur, India.
authors.forename: Vinith
authors.initials: V
authors.lastname: Vemana
authors.affiliation: Intelligent Systems Research Centre (ISRC), University of Ulster, Derry-Londonderry, UK.|College of Science and Technology, Nottingham Trent University, Nottingham, UK.
authors.forename: T M
authors.identifier: 0000-0002-9897-4748
authors.initials: TM
authors.lastname: McGinnity
authors.affiliation: Intelligent Systems Research Centre (ISRC), University of Ulster, Derry-Londonderry, UK.
authors.forename: Girijesh
authors.identifier: 0000-0003-3284-9589
authors.initials: G
authors.lastname: Prasad
authors.affiliation: Intelligent Systems Research Centre (ISRC), University of Ulster, Derry-Londonderry, UK k.wong-lin@ulster.ac.uk.
authors.forename: KongFatt
authors.identifier: 0000-0001-8724-4398
authors.initials: K
authors.lastname: Wong-Lin
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000503:physiopathology*; D003198:Computer Simulation; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D014584:User-Computer Interface
chemical_list: D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D018377:Neurotransmitter Agents
keywords: computational neural circuit models; neuromodulators; neuropharmacology; norepinephrine/noradrenaline; orexin/hypocretin; serotonin