Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.
Cell Rep. 2022 Feb 15;38(7):110380. doi: 10.1016/j.celrep.2022.110380.
The nucleus accumbens (NAc) is a key region in motivated behaviors. NAc medium spiny neurons (MSNs) are divided into those expressing dopamine receptor D1 or D2. Classically, D1- and D2-MSNs have been described as having opposing roles in reinforcement, but recent evidence suggests a more complex role for D2-MSNs. Here, we show that optogenetic modulation of D2-MSN to ventral pallidum (VP) projections during different stages of motivated behavior has contrasting effects in motivation. Activation of D2-MSN-VP projections during a reward-predicting cue results in increased motivational drive, whereas activation at reward delivery decreases motivation; optical inhibition triggers the opposite behavioral effect. In addition, in a free-choice instrumental task, animals prefer the lever that originates one pellet in opposition to pellet plus D2-MSN-VP optogenetic activation and vice versa for optogenetic inhibition. In summary, D2-MSN-VP projections play different, and even opposing, roles in distinct phases of motivated behavior.
伏隔核（NAc）是动机行为的关键区域。NAc 中的中脑多巴胺神经元（MSNs）可分为表达多巴胺受体 D1 或 D2 的神经元。经典理论认为，D1 和 D2-MSNs 在强化中具有相反的作用，但最近的证据表明 D2-MSNs 具有更复杂的作用。在这里，我们表明，在动机行为的不同阶段，对腹侧苍白球（VP）投射的 D2-MSN 进行光遗传学调制，对动机具有相反的影响。在奖励预测线索期间激活 D2-MSN-VP 投射会增加动机驱动力，而在奖励传递时激活则会降低动机；光学抑制会引发相反的行为效应。此外，在自由选择的工具任务中，动物更喜欢产生一个药丸的杠杆，而不是药丸加 D2-MSN-VP 光遗传学激活，反之亦然，对于光遗传学抑制也是如此。总之，D2-MSN-VP 投射在动机行为的不同阶段发挥不同的作用，甚至作用相反。
