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An integrated modelling framework for neural circuits with multiple neuromodulators. J R Soc Interface 2017 01;14(126)



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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.

Author List

Joshi A, Youssofzadeh V, Vemana V, McGinnity TM, Prasad G, Wong-Lin K


Vahab Youssofzadeh PhD Assistant Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antidepressive Agents
Computer Simulation
Dopamine Uptake Inhibitors
Models, Neurological
Neurotransmitter Agents
User-Computer Interface
jenkins-FCD Prod-468 69a93cef3257f26b866d455c1d2b2d0f28382f14