How complex can the co-modulation of dopamine and serotonin on prefrontal cortical rhythms be?

Da-Hui Wang, KongFatt Wong-Lin

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

Abstract

The prefrontal cortex (PFC) plays an important role in executive and higher cognitive functions. The PFC is also heavily innervated by the dopaminergic (DA) and serotonergic (5-HT) systems. Abnormal PFC activities and rhythms, and dysfunctions in the DA and 5-HT systems have been implicated in some neurological and neuropsychiatric disorders. Despite the high level of interest in these brain systems, the combined DA and 5-HT influences on PFC dynamics remain unknown. In this work, we incorporate essential available experimental findings into a mathematical model to systematically analyse the combined modulation of DA and 5-HT, with a focus on the beta and gamma band oscillations. Our results are as follows. First, we find that single pyramidal cells with 5-HT1A and 2A receptors can be modulated by 5-HT non-monotonically. Secondly, two-population excitatory-inhibitory type networks consisting of pyramidal cells expressing D1 receptors can exhibit rich network oscillation behaviors. In particular, 5-HT and DA can modulate the amplitude and frequency of the oscillations, which can emerge or cease, depending on receptor types. Certain receptor combinations are conducive for the robustness of the oscillatory regime, and for the existence of multiple discrete oscillatory regimes. Thirdly, high DA concentration can support robust network oscillation in a heterogeneous multi-population model that takes into account possible combination of receptors. Fourthly, selective D1 receptor antagonists (agonists) tend to suppress (enhance) network oscillations, and shift from beta toward gamma band, while selective 5-HT1A antagonists (agonists) act in opposite ways. Finally, selective D2 or 5-HT2A receptor antagonists (agonists) can lead to a decrease (increase) in oscillation amplitude, but only 5-HT2A antagonists (agonists) can increase (decrease) the frequency. These results are comparable to some pharmacological effects. Our results illustrate the complex mechanisms of DA and 5-HT when operating simultaneously through multiple receptors.
LanguageEnglish
Title of host publicationUnknown Host Publication
Number of pages1
Publication statusPublished - 2013
EventSociety for Neuroscience Annual Meeting 2013 - San Diego, California, USA
Duration: 1 Jan 2013 → …

Conference

ConferenceSociety for Neuroscience Annual Meeting 2013
Period1/01/13 → …

Fingerprint

Dopamine
Serotonin
Prefrontal Cortex
Serotonin 5-HT2 Receptor Antagonists
Pyramidal Cells
Serotonin 5-HT1 Receptor Antagonists
Receptor, Serotonin, 5-HT2A
Receptor, Serotonin, 5-HT1A
Nervous System Diseases
Cognition
Population
Theoretical Models
Pharmacology
Brain

Cite this

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title = "How complex can the co-modulation of dopamine and serotonin on prefrontal cortical rhythms be?",
abstract = "The prefrontal cortex (PFC) plays an important role in executive and higher cognitive functions. The PFC is also heavily innervated by the dopaminergic (DA) and serotonergic (5-HT) systems. Abnormal PFC activities and rhythms, and dysfunctions in the DA and 5-HT systems have been implicated in some neurological and neuropsychiatric disorders. Despite the high level of interest in these brain systems, the combined DA and 5-HT influences on PFC dynamics remain unknown. In this work, we incorporate essential available experimental findings into a mathematical model to systematically analyse the combined modulation of DA and 5-HT, with a focus on the beta and gamma band oscillations. Our results are as follows. First, we find that single pyramidal cells with 5-HT1A and 2A receptors can be modulated by 5-HT non-monotonically. Secondly, two-population excitatory-inhibitory type networks consisting of pyramidal cells expressing D1 receptors can exhibit rich network oscillation behaviors. In particular, 5-HT and DA can modulate the amplitude and frequency of the oscillations, which can emerge or cease, depending on receptor types. Certain receptor combinations are conducive for the robustness of the oscillatory regime, and for the existence of multiple discrete oscillatory regimes. Thirdly, high DA concentration can support robust network oscillation in a heterogeneous multi-population model that takes into account possible combination of receptors. Fourthly, selective D1 receptor antagonists (agonists) tend to suppress (enhance) network oscillations, and shift from beta toward gamma band, while selective 5-HT1A antagonists (agonists) act in opposite ways. Finally, selective D2 or 5-HT2A receptor antagonists (agonists) can lead to a decrease (increase) in oscillation amplitude, but only 5-HT2A antagonists (agonists) can increase (decrease) the frequency. These results are comparable to some pharmacological effects. Our results illustrate the complex mechanisms of DA and 5-HT when operating simultaneously through multiple receptors.",
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}

Wang, D-H & Wong-Lin, K 2013, How complex can the co-modulation of dopamine and serotonin on prefrontal cortical rhythms be? in Unknown Host Publication. Society for Neuroscience Annual Meeting 2013, 1/01/13.

How complex can the co-modulation of dopamine and serotonin on prefrontal cortical rhythms be? / Wang, Da-Hui; Wong-Lin, KongFatt.

Unknown Host Publication. 2013.

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

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