RRC ID 54171
Author Bin Saifullah MA, Nagai T, Kuroda K, Wulaer B, Nabeshima T, Kaibuchi K, Yamada K.
Title Cell type-specific activation of mitogen-activated protein kinase in D1 receptor-expressing neurons of the nucleus accumbens potentiates stimulus-reward learning in mice.
Journal Sci Rep
Abstract 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.
Volume 8(1)
Pages 14413
Published 2018-9-26
DOI 10.1038/s41598-018-32840-1
PII 10.1038/s41598-018-32840-1
PMID 30258218
PMC PMC6158283
MeSH Animals Conditioning, Classical Dopaminergic Neurons / cytology Dopaminergic Neurons / metabolism* Learning* MAP Kinase Signaling System* Male Mice, Inbred C57BL Motivation Nucleus Accumbens / cytology* Nucleus Accumbens / physiology Phosphorylation Receptors, Dopamine D1 / metabolism* Receptors, Dopamine D2 / metabolism Reward
IF 3.998
Times Cited 1
Mice RBRC02332 RBRC03111