A distinct D1-MSN subpopulation down-regulates dopamine to promote negative emotional state.

A distinct D1-MSN subpopulation down-regulates dopamine to promote negative emotional state.
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独特的 D1-MSN 亚群下调多巴胺以促进负面情绪状态

DOI:
10.1038/s41422-021-00588-5
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发表时间:
2022-03
期刊:
影响因子:
44.1
通讯作者:
Liu X
Liu X
中科院分区:
生物学1区
文献类型:
--
作者:
Liu Z;Le Q;Lv Y;Chen X;Cui J;Zhou Y;Cheng D;Ma C;Su X;Xiao L;Yang R;Zhang J;Ma L;Liu X

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丘脑底核(NAc)中的多巴胺(DA)水平对奖赏和厌恶编码至关重要。腹侧中脑(VM)DA能神经元释放的DA增加了NAc中VM投射的表达D1-多巴胺受体的中型棘神经元(D1-MSNs)的兴奋性,以增强DA释放和增加奖励。然而,如何调节这样的DA正反馈回路,以维持DA稳态和奖赏-厌恶平衡仍然是难以捉摸的。在这里,我们报告的腹侧苍白球(VP)的NAc D1-MSNs(D1 NAc-VP)的投射被抑制的奖励刺激和激活的厌恶刺激。与D1-MSN的VM投射(D1 NAc-VM)相反,D1 NAc-VP投射的激活诱导厌恶,但不诱导奖励。D1 NAc-VPMSN与D1 NAc-VMMSN不同,D1 NAc-VMMSN表现出D1-MSN的常规功能。D1 NAc-VP投射的激活刺激VM GABA能传递,抑制VM DA能神经元,并减少DA释放到NAc中。因此,D1 NAc-VP和D1 NAc-VMMSNs协同控制NAc多巴胺平衡和奖赏-厌恶状态。
Dopamine (DA) level in the nucleus accumbens (NAc) is critical for reward and aversion encoding. DA released from the ventral mesencephalon (VM) DAergic neurons increases the excitability of VM-projecting D1-dopamine receptor-expressing medium spiny neurons (D1-MSNs) in the NAc to enhance DA release and augment rewards. However, how such a DA positive feedback loop is regulated to maintain DA homeostasis and reward-aversion balance remains elusive. Here we report that the ventral pallidum (VP) projection of NAc D1-MSNs (D1NAc-VP) is inhibited by rewarding stimuli and activated by aversive stimuli. In contrast to the VM projection of D1-MSN (D1NAc-VM), activation of D1NAc-VPprojection induces aversion, but not reward. D1NAc-VPMSNs are distinct from the D1NAc-VMMSNs, which exhibit conventional functions of D1-MSNs. Activation of D1NAc-VPprojection stimulates VM GABAergic transmission, inhibits VM DAergic neurons, and reduces DA release into the NAc. Thus, D1NAc-VPand D1NAc-VMMSNs cooperatively control NAc dopamine balance and reward-aversion states.
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