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研究揭示D2Rs在辨别学习和刺突扩大中的作用
2020-03-19 15:40

日本东京大学Sho YagishitaHaruo Kasai研究组合作揭示多巴胺D2受体(D2Rs)在辨别学习和刺突扩大中的作用。相关论文发表在2020318日出版的《自然》杂志上。

他们表明,语气奖励调节以一种依赖于小鼠伏隔核(NAc)中的多巴胺D1受体(D1Rs)的方式诱导明显的刺激泛化,而辨别学习通过使用多巴胺浓度(多巴胺浸润)来改善调节。在NAc切片中,D2R检测到狭窄的多巴胺浸润(短至0.4 s)以抑制表达D2R的刺突投射神经元(D2-SPNs)中腺苷A2A受体(A2AR)介导的树突刺突增大。辨别学习需要NAcCa2+ /钙调蛋白依赖性蛋白激酶IIA2ARs的可塑性相关信号传导。相比之下,灭绝学习不涉及多巴胺浸润或D2-SPN。甲基苯丙胺治疗可引起多巴胺信号失调、辨别学习障碍和刺突增大,D2R拮抗剂可逆转这些损害。他们的数据表明,D2R促进了D1R介导的广义奖励学习。

据悉,多巴胺D2受体(D2Rs)在纹状体中密集表达,并与神经精神疾病(例如精神分裂症)有关。多巴胺的高亲和力结合表明,在惩罚学习过程中D2Rs检测到多巴胺浸润的瞬时降低。但是,尚不清楚D2R依赖行为的性质和细胞基础。

附:英文原文

Title: Dopamine D2 receptors in discrimination learning and spine enlargement

Author: Yusuke Iino, Takeshi Sawada, Kenji Yamaguchi, Mio Tajiri, Shin Ishii, Haruo Kasai, Sho Yagishita

Issue&Volume: 2020-03-18

Abstract: Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia1,2. High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning3,4,5. However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca2+/calmodulin-dependent protein kinase II and A2ARs in the NAc was required for discrimination learning. By contrast, extinction learning did not involve dopamine dips or D2-SPNs. Treatment with methamphetamine, which dysregulates dopamine signalling, impaired discrimination learning and spine enlargement, and these impairments were reversed by a D2R antagonist. Our data show that D2Rs refine the generalized reward learning mediated by D1Rs.

DOI: 10.1038/s41586-020-2115-1

Source: https://www.nature.com/articles/s41586-020-2115-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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