Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior

Bokyeong Kim; Sehyoun Yoon; Ryuichi Nakajima; Hyo Jin Lee; Hee Jeong Lim; Yeon Kyung Lee; June Seek Choi; Bong June Yoon; George J. Augustine; Ja Hyun Baik

doi:10.1073/pnas.1811664115

Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior

Bokyeong Kim, Sehyoun Yoon, Ryuichi Nakajima, Hyo Jin Lee, Hee Jeong Lim, Yeon Kyung Lee, June Seek Choi, Bong June Yoon, George J. Augustine, Ja Hyun Baik

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2^-/-) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.

Original language	English
Pages (from-to)	E10730-E10739
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	115
Issue number	45
DOIs	https://doi.org/10.1073/pnas.1811664115
Publication status	Published - 2018 Nov 6

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank the staff of the Gyerim Experimental Animal Resource Center for animal care and technical assistance; Joon-Hyun Paik (Duke University) for technical assistance; Dr. Akihiro Yamanaka (Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Japan) for help with the optogenetic behavioral analysis; and Byeong Jun Kang and Dr. Bok Soon Go (Korea University) for help and discussion. The construct pAAV-EF1a-DIO-hChR2(H134R)-EYFP-WPRE was generously provided by Dr. Karl Deisseroth (Stanford University). This work was supported by Brain Research Program Grant 2013M3C7A1056101; Bio & Medical Technology Development Program Grants 2013M3A9D5072550 and 2016M3A9D5A01952412; Mid-Career Researcher Program Grants 2014R1A2A2A01003337 and NRF-2017R1A2B4008875; Science Research Center Grant 2015R1A5A1009024; a Korea University (KU) Future Research Grant (to J.-H.B.); World Class Institute Program Grant WCI 2009-003 of the National Research Foundation of Korea funded by the Ministry of Science, Information and Communication Technology, and Future Planning of the Republic of Korea; and Singapore Ministry of Education Grant MOE2015-T2-2-095.

Publisher Copyright:
© 2018 BioMed Central Ltd..All right reserved.

Keywords

Central amygdala
Dopamine receptor
Impulsivity
Neural circuit
Optogenetics

ASJC Scopus subject areas

General

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10.1073/pnas.1811664115

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Kim, B., Yoon, S., Nakajima, R., Lee, H. J., Lim, H. J., Lee, Y. K., Choi, J. S., Yoon, B. J., Augustine, G. J., & Baik, J. H. (2018). Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior. Proceedings of the National Academy of Sciences of the United States of America, 115(45), E10730-E10739. https://doi.org/10.1073/pnas.1811664115

Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior. / Kim, Bokyeong; Yoon, Sehyoun; Nakajima, Ryuichi et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 45, 06.11.2018, p. E10730-E10739.

Research output: Contribution to journal › Article › peer-review

Kim, B, Yoon, S, Nakajima, R, Lee, HJ, Lim, HJ, Lee, YK, Choi, JS, Yoon, BJ, Augustine, GJ & Baik, JH 2018, 'Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 45, pp. E10730-E10739. https://doi.org/10.1073/pnas.1811664115

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title = "Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior",

abstract = "Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2-/-) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.",

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note = "Funding Information: ACKNOWLEDGMENTS. We thank the staff of the Gyerim Experimental Animal Resource Center for animal care and technical assistance; Joon-Hyun Paik (Duke University) for technical assistance; Dr. Akihiro Yamanaka (Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Japan) for help with the optogenetic behavioral analysis; and Byeong Jun Kang and Dr. Bok Soon Go (Korea University) for help and discussion. The construct pAAV-EF1a-DIO-hChR2(H134R)-EYFP-WPRE was generously provided by Dr. Karl Deisseroth (Stanford University). This work was supported by Brain Research Program Grant 2013M3C7A1056101; Bio & Medical Technology Development Program Grants 2013M3A9D5072550 and 2016M3A9D5A01952412; Mid-Career Researcher Program Grants 2014R1A2A2A01003337 and NRF-2017R1A2B4008875; Science Research Center Grant 2015R1A5A1009024; a Korea University (KU) Future Research Grant (to J.-H.B.); World Class Institute Program Grant WCI 2009-003 of the National Research Foundation of Korea funded by the Ministry of Science, Information and Communication Technology, and Future Planning of the Republic of Korea; and Singapore Ministry of Education Grant MOE2015-T2-2-095. Publisher Copyright: {\textcopyright} 2018 BioMed Central Ltd..All right reserved.",

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N2 - Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2-/-) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.

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Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior

Abstract

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