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

Date

01/20/2017

Pubmed ID

28100828

Pubmed Central ID

PMC5310738

DOI

10.1098/rsif.2016.0902

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.

Author List

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

Author

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

Animals
Antidepressive Agents
Brain
Computer Simulation
Dopamine Uptake Inhibitors
Humans
Models, Neurological
Neurotransmitter Agents
User-Computer Interface
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