A Mathematical Model to Explore the Interdependence Between the Serotonin and Orexin/Hypocretin Systems

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

9 Citations (Scopus)

Abstract

Among their multitude of physiological and behavioral effects, the neurochemicals serotonin (5-HT) and orexin (Ox) have been closely linked to major depressive disorders (MDD) and sleep alterations. The dorsal raphe nucleus (DRN) and the later hypothalamus area (LHA) are brain regions that are sources of 5-HT and Ox, and there is evidence that suggests a reciprocal interaction between them. This lends support to the hypothesis of a close relationship between MDD and sleeping disorder. Based on various experimental data, and appropriate assumptions, we construct a mathematical model of the coupled DRN-LHA neural circuit. Our model relates the dynamics of four important variables that can be experimentally measured: (i) the firing rate of 5-HT-containing neurons in DRN, (ii) the firing rate of Ox-containing neurons in the LHA, (iii) 5-HT concentration level in LHA, and (iv) Ox concentration level in DRN. Simulations show that our model supports the co-existence of baseline activities and concentration levels as observed in various separate experiments. It also allows circuit-level exploration of various parameters not yet identified experimentally, e.g. the rise and decay of Ox concentration levels due to Ox neural activity, and the exact dependence of Ox neural activity on 5-HT level. Finally we have made some model predictions regarding the effects of the 5-HT antagonist on the circuit. Our model, which can be subjected to verification and refinement as new experimental data accumulates, provides unified quantitative relationships and predictions between two important connected brain regions strongly tied to MDD and sleep disorders.
LanguageEnglish
Title of host publicationIEEE Engineering in Medicine and Biology Society
Place of PublicationNew York
Pages7270-7273
Number of pages4
ISBN (Electronic)978-1-4577-1589-1
DOIs
Publication statusPublished - 30 Aug 2011
Event33rd Annual International Conference of the IEEE EMBC Boston, Massachusetts - Boston, MA, USA
Duration: 30 Aug 2011 → …

Conference

Conference33rd Annual International Conference of the IEEE EMBC Boston, Massachusetts
Period30/08/11 → …

Fingerprint

Serotonin
Theoretical Models
Hypothalamus
Major Depressive Disorder
Neurons
Serotonin Antagonists
Brain
Orexins
Sleep
Dorsal Raphe Nucleus

Cite this

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title = "A Mathematical Model to Explore the Interdependence Between the Serotonin and Orexin/Hypocretin Systems",
abstract = "Among their multitude of physiological and behavioral effects, the neurochemicals serotonin (5-HT) and orexin (Ox) have been closely linked to major depressive disorders (MDD) and sleep alterations. The dorsal raphe nucleus (DRN) and the later hypothalamus area (LHA) are brain regions that are sources of 5-HT and Ox, and there is evidence that suggests a reciprocal interaction between them. This lends support to the hypothesis of a close relationship between MDD and sleeping disorder. Based on various experimental data, and appropriate assumptions, we construct a mathematical model of the coupled DRN-LHA neural circuit. Our model relates the dynamics of four important variables that can be experimentally measured: (i) the firing rate of 5-HT-containing neurons in DRN, (ii) the firing rate of Ox-containing neurons in the LHA, (iii) 5-HT concentration level in LHA, and (iv) Ox concentration level in DRN. Simulations show that our model supports the co-existence of baseline activities and concentration levels as observed in various separate experiments. It also allows circuit-level exploration of various parameters not yet identified experimentally, e.g. the rise and decay of Ox concentration levels due to Ox neural activity, and the exact dependence of Ox neural activity on 5-HT level. Finally we have made some model predictions regarding the effects of the 5-HT antagonist on the circuit. Our model, which can be subjected to verification and refinement as new experimental data accumulates, provides unified quantitative relationships and predictions between two important connected brain regions strongly tied to MDD and sleep disorders.",
author = "Alok Joshi and Kongfatt Wong-Lin and TM McGinnity and G Prasad",
year = "2011",
month = "8",
day = "30",
doi = "10.1109/IEMBS.2011.6091837",
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Joshi, A, Wong-Lin, K, McGinnity, TM & Prasad, G 2011, A Mathematical Model to Explore the Interdependence Between the Serotonin and Orexin/Hypocretin Systems. in IEEE Engineering in Medicine and Biology Society. New York, pp. 7270-7273, 33rd Annual International Conference of the IEEE EMBC Boston, Massachusetts, 30/08/11. https://doi.org/10.1109/IEMBS.2011.6091837

A Mathematical Model to Explore the Interdependence Between the Serotonin and Orexin/Hypocretin Systems. / Joshi, Alok; Wong-Lin, Kongfatt; McGinnity, TM; Prasad, G.

IEEE Engineering in Medicine and Biology Society. New York, 2011. p. 7270-7273.

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

TY - GEN

T1 - A Mathematical Model to Explore the Interdependence Between the Serotonin and Orexin/Hypocretin Systems

AU - Joshi, Alok

AU - Wong-Lin, Kongfatt

AU - McGinnity, TM

AU - Prasad, G

PY - 2011/8/30

Y1 - 2011/8/30

N2 - Among their multitude of physiological and behavioral effects, the neurochemicals serotonin (5-HT) and orexin (Ox) have been closely linked to major depressive disorders (MDD) and sleep alterations. The dorsal raphe nucleus (DRN) and the later hypothalamus area (LHA) are brain regions that are sources of 5-HT and Ox, and there is evidence that suggests a reciprocal interaction between them. This lends support to the hypothesis of a close relationship between MDD and sleeping disorder. Based on various experimental data, and appropriate assumptions, we construct a mathematical model of the coupled DRN-LHA neural circuit. Our model relates the dynamics of four important variables that can be experimentally measured: (i) the firing rate of 5-HT-containing neurons in DRN, (ii) the firing rate of Ox-containing neurons in the LHA, (iii) 5-HT concentration level in LHA, and (iv) Ox concentration level in DRN. Simulations show that our model supports the co-existence of baseline activities and concentration levels as observed in various separate experiments. It also allows circuit-level exploration of various parameters not yet identified experimentally, e.g. the rise and decay of Ox concentration levels due to Ox neural activity, and the exact dependence of Ox neural activity on 5-HT level. Finally we have made some model predictions regarding the effects of the 5-HT antagonist on the circuit. Our model, which can be subjected to verification and refinement as new experimental data accumulates, provides unified quantitative relationships and predictions between two important connected brain regions strongly tied to MDD and sleep disorders.

AB - Among their multitude of physiological and behavioral effects, the neurochemicals serotonin (5-HT) and orexin (Ox) have been closely linked to major depressive disorders (MDD) and sleep alterations. The dorsal raphe nucleus (DRN) and the later hypothalamus area (LHA) are brain regions that are sources of 5-HT and Ox, and there is evidence that suggests a reciprocal interaction between them. This lends support to the hypothesis of a close relationship between MDD and sleeping disorder. Based on various experimental data, and appropriate assumptions, we construct a mathematical model of the coupled DRN-LHA neural circuit. Our model relates the dynamics of four important variables that can be experimentally measured: (i) the firing rate of 5-HT-containing neurons in DRN, (ii) the firing rate of Ox-containing neurons in the LHA, (iii) 5-HT concentration level in LHA, and (iv) Ox concentration level in DRN. Simulations show that our model supports the co-existence of baseline activities and concentration levels as observed in various separate experiments. It also allows circuit-level exploration of various parameters not yet identified experimentally, e.g. the rise and decay of Ox concentration levels due to Ox neural activity, and the exact dependence of Ox neural activity on 5-HT level. Finally we have made some model predictions regarding the effects of the 5-HT antagonist on the circuit. Our model, which can be subjected to verification and refinement as new experimental data accumulates, provides unified quantitative relationships and predictions between two important connected brain regions strongly tied to MDD and sleep disorders.

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BT - IEEE Engineering in Medicine and Biology Society

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