Kim, B., Yoon, S., Nakajima, R., Lee, H. J., Lim, H. J., Lee, Y.-K., … 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, 115(45), E10730–E10739. doi:10.1073/pnas.1811664115
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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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.