The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.

In behavioral learning, reward-related events are encoded into phasic dopamine (DA) signals in the brain. In particular, unexpected reward omission leads to a phasic decrease in DA (DA dip) in the striatum, which triggers long-term potentiation (LTP) in DA D2 receptor (D2R)-expressing spiny-projecti...

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Autores principales:	Hidetoshi Urakubo, Sho Yagishita, Haruo Kasai, Yoshiyuki Kubota, Shin Ishii
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3e978ad28d9b4f8bbd0241d856ec8d43
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spelling	oai:doaj.org-article:3e978ad28d9b4f8bbd0241d856ec8d432021-12-02T19:57:43ZThe critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.1553-734X1553-735810.1371/journal.pcbi.1009364https://doaj.org/article/3e978ad28d9b4f8bbd0241d856ec8d432021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009364https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358In behavioral learning, reward-related events are encoded into phasic dopamine (DA) signals in the brain. In particular, unexpected reward omission leads to a phasic decrease in DA (DA dip) in the striatum, which triggers long-term potentiation (LTP) in DA D2 receptor (D2R)-expressing spiny-projection neurons (D2 SPNs). While this LTP is required for reward discrimination, it is unclear how such a short DA-dip signal (0.5-2 s) is transferred through intracellular signaling to the coincidence detector, adenylate cyclase (AC). In the present study, we built a computational model of D2 signaling to determine conditions for the DA-dip detection. The DA dip can be detected only if the basal DA signal sufficiently inhibits AC, and the DA-dip signal sufficiently disinhibits AC. We found that those two requirements were simultaneously satisfied only if two key molecules, D2R and regulators of G protein signaling (RGS) were balanced within a certain range; this balance has indeed been observed in experimental studies. We also found that high level of RGS was required for the detection of a 0.5-s short DA dip, and the analytical solutions for these requirements confirmed their universality. The imbalance between D2R and RGS is associated with schizophrenia and DYT1 dystonia, both of which are accompanied by abnormal striatal LTP. Our simulations suggest that D2 SPNs in patients with schizophrenia and DYT1 dystonia cannot detect short DA dips. We finally discussed that such psychiatric and movement disorders can be understood in terms of the imbalance between D2R and RGS.Hidetoshi UrakuboSho YagishitaHaruo KasaiYoshiyuki KubotaShin IshiiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009364 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Hidetoshi Urakubo Sho Yagishita Haruo Kasai Yoshiyuki Kubota Shin Ishii The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.
description	In behavioral learning, reward-related events are encoded into phasic dopamine (DA) signals in the brain. In particular, unexpected reward omission leads to a phasic decrease in DA (DA dip) in the striatum, which triggers long-term potentiation (LTP) in DA D2 receptor (D2R)-expressing spiny-projection neurons (D2 SPNs). While this LTP is required for reward discrimination, it is unclear how such a short DA-dip signal (0.5-2 s) is transferred through intracellular signaling to the coincidence detector, adenylate cyclase (AC). In the present study, we built a computational model of D2 signaling to determine conditions for the DA-dip detection. The DA dip can be detected only if the basal DA signal sufficiently inhibits AC, and the DA-dip signal sufficiently disinhibits AC. We found that those two requirements were simultaneously satisfied only if two key molecules, D2R and regulators of G protein signaling (RGS) were balanced within a certain range; this balance has indeed been observed in experimental studies. We also found that high level of RGS was required for the detection of a 0.5-s short DA dip, and the analytical solutions for these requirements confirmed their universality. The imbalance between D2R and RGS is associated with schizophrenia and DYT1 dystonia, both of which are accompanied by abnormal striatal LTP. Our simulations suggest that D2 SPNs in patients with schizophrenia and DYT1 dystonia cannot detect short DA dips. We finally discussed that such psychiatric and movement disorders can be understood in terms of the imbalance between D2R and RGS.
format	article
author	Hidetoshi Urakubo Sho Yagishita Haruo Kasai Yoshiyuki Kubota Shin Ishii
author_facet	Hidetoshi Urakubo Sho Yagishita Haruo Kasai Yoshiyuki Kubota Shin Ishii
author_sort	Hidetoshi Urakubo
title	The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.
title_short	The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.
title_full	The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.
title_fullStr	The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.
title_full_unstemmed	The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.
title_sort	critical balance between dopamine d2 receptor and rgs for the sensitive detection of a transient decay in dopamine signal.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3e978ad28d9b4f8bbd0241d856ec8d43
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The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.

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