TY - JOUR
T1 - Cell type-specific activation of mitogen-activated protein kinase in D1 receptor-expressing neurons of the nucleus accumbens potentiates stimulus-reward learning in mice
AU - Bin Saifullah, Md Ali
AU - Nagai, Taku
AU - Kuroda, Keisuke
AU - Wulaer, Bolati
AU - Nabeshima, Toshitaka
AU - Kaibuchi, Kozo
AU - Yamada, Kiyofumi
N1 - Funding Information:
This work was supported by the following funding sources: KAKENHI Grant Numbers JP17H04031, JP17H02220, JP16K15201, JP15H01284, 17K19483 and 25116515 from JSPS, the 18dm0107087 and JP18mk0101076 from AMED, a Grant for Biomedical Research from SRF, the Astellas Foundation for Research on Metabolic Disorders, The Pharmacological Research Foundation, The Uehara Memorial Foundation. We thank Dr. Eisuke Nishida for providing the constructs for AAV-CAGGS-Flex-EGFP-P2A-MAP2K1 mutants. We thank Dr. Kazuto Kobayashi for providing Drd1a-YFP and Drd2-YFP mutant mice. We thank the Division for Research of Laboratory Animals, Center for Research of Laboratory Animals and Medical Research Engineering (technical staff: Yasutaka Ohya and Kumiko Yano), for animal care and use.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Medium spiny neurons (MSN) in the nucleus accumbens (NAc) are a fundamental component of various aspects of motivated behavior. Although mitogen-activated protein kinase (MAPK) signaling plays a crucial role in several types of learning, the cell type-specific role of MAPK pathway in stimulus-reward learning and motivation remains unclear. We herein investigated the role of MAPK in accumbal MSNs in reward-associated learning and memory. During the acquisition of Pavlovian conditioning, the number of phosphorylated MAPK1/3-positive cells was increased significantly and exclusively in the NAc core by 7-days of extensive training. MAPK signaling in the respective D1R- and D2R-MSNs was manipulated by transfecting an adeno-associated virus (AAV) plasmid into the NAc of Drd1a-Cre and Drd2-Cre transgenic mice. Potentiation of MAPK signaling shifted the learning curve of Pavlovian conditioning to the left only in Drd1a-Cre mice, whereas such manipulation in D2R-MSNs had negligible effects. In contrast, MAPK manipulation in D2R-MSNs of the NAc core significantly increased motivation for food rewards as found in Drd1a-Cre mice. These results suggest that MAPK signaling in the D1R-MSNs of NAc core plays an important role in stimulus-reward learning, while MAPK signaling in both D1R- and D2R-MSNs is involved in motivation for natural rewards.
AB - Medium spiny neurons (MSN) in the nucleus accumbens (NAc) are a fundamental component of various aspects of motivated behavior. Although mitogen-activated protein kinase (MAPK) signaling plays a crucial role in several types of learning, the cell type-specific role of MAPK pathway in stimulus-reward learning and motivation remains unclear. We herein investigated the role of MAPK in accumbal MSNs in reward-associated learning and memory. During the acquisition of Pavlovian conditioning, the number of phosphorylated MAPK1/3-positive cells was increased significantly and exclusively in the NAc core by 7-days of extensive training. MAPK signaling in the respective D1R- and D2R-MSNs was manipulated by transfecting an adeno-associated virus (AAV) plasmid into the NAc of Drd1a-Cre and Drd2-Cre transgenic mice. Potentiation of MAPK signaling shifted the learning curve of Pavlovian conditioning to the left only in Drd1a-Cre mice, whereas such manipulation in D2R-MSNs had negligible effects. In contrast, MAPK manipulation in D2R-MSNs of the NAc core significantly increased motivation for food rewards as found in Drd1a-Cre mice. These results suggest that MAPK signaling in the D1R-MSNs of NAc core plays an important role in stimulus-reward learning, while MAPK signaling in both D1R- and D2R-MSNs is involved in motivation for natural rewards.
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U2 - 10.1038/s41598-018-32840-1
DO - 10.1038/s41598-018-32840-1
M3 - Article
C2 - 30258218
AN - SCOPUS:85054084919
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 14413
ER -