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Medium spiny neurons of the anterior dorsomedial striatum mediate reversal learning in a cell-type-dependent manner
Wang, Xingyue1,2; Qiao, Yanhua1,2; Dai, Zhonghua1,2; Sui, Nan1,2; Shen, Fang1,2; Zhang, Jianjun1,2; Liang, Jing1,2
通讯作者Liang, Jing(liangj@psych.ac.cn)
2019
发表期刊BRAIN STRUCTURE & FUNCTION
ISSN1863-2653
卷号224期号:1页码:419-434
摘要The striatum has been implicated in the regulation of cognitive flexibility. Abnormalities in the anterior dorsomedial striatum (aDMS) are revealed in many mental disorders in which cognitive inflexibility is commonly observed. However, it remains poorly understood whether the aDMS plays a special role in flexible cognitive control and what the regulation pattern is in different neuronal populations. Based on the reversal learning task in mice, we showed that optogenetic activation in dopamine receptor 1-expressing medium spiny neurons (D1R-MSNs) of the aDMS impaired flexibility; meanwhile, suppressing these neurons facilitated behavioral performance. Conversely, D2R-MSN activation accelerated reversal learning, but it induced no change through neuronal suppression. The acquisition and retention of discrimination learning were unaffected by the manipulation of any type of MSN. Through bi-direct optogenetic modulation in D1R-MSNs of the same subject in a serial reversal learning task, we further revealed the function of D1R-MSNs during different stages of reversal learning, where inhibiting and exciting the same group of neurons reduced perseverative errors and increased regressive errors. Following D1R- and D2R-MSN activation in the aDMS, neuronal activity of the mediodorsal thalamus decreased and increased, respectively, in parallel with behavioral impairment and facilitation, but not as a direct result of the activation of the striatal MSNs. We propose that D1R- and D2R-MSN sub-populations in the aDMS exert opposing functions in cognitive flexibility regulation, with more important and complex roles of D1R-MSNs involved. Mental disorders with cognitive flexibility problems may feature an underlying functional imbalance in the aDMS' two types of neurons.
关键词Anterior dorsomedial striatum Behavioral flexibility Optogenetics Medium spiny neurons Dopamine receptors
DOI10.1007/s00429-018-1780-4
收录类别SCI
语种英语
项目资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National Key Basic Research Program of China
资助项目National Natural Science Foundation of China[31571108] ; Beijing Natural Science Foundation[5162023] ; National Key Basic Research Program of China[2015CB553501]
WOS研究方向Anatomy & Morphology ; Neurosciences & Neurology
WOS类目Anatomy & Morphology ; Neurosciences
WOS记录号WOS:000458286500027
出版者SPRINGER HEIDELBERG
关键词[WOS]BEHAVIORAL FLEXIBILITY ; BASAL GANGLIA ; PARKINSONS-DISEASE ; DORSAL STRIATUM ; DISTINCT ROLES ; VISUAL-DISCRIMINATION ; ORBITOFRONTAL CORTEX ; MEDIODORSAL THALAMUS ; NUCLEUS-ACCUMBENS ; INDIRECT PATHWAYS
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文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/28353
专题中国科学院心理健康重点实验室
通讯作者Liang, Jing
作者单位1.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
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Wang, Xingyue,Qiao, Yanhua,Dai, Zhonghua,et al. Medium spiny neurons of the anterior dorsomedial striatum mediate reversal learning in a cell-type-dependent manner[J]. BRAIN STRUCTURE & FUNCTION,2019,224(1):419-434.
APA Wang, Xingyue.,Qiao, Yanhua.,Dai, Zhonghua.,Sui, Nan.,Shen, Fang.,...&Liang, Jing.(2019).Medium spiny neurons of the anterior dorsomedial striatum mediate reversal learning in a cell-type-dependent manner.BRAIN STRUCTURE & FUNCTION,224(1),419-434.
MLA Wang, Xingyue,et al."Medium spiny neurons of the anterior dorsomedial striatum mediate reversal learning in a cell-type-dependent manner".BRAIN STRUCTURE & FUNCTION 224.1(2019):419-434.
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