Cell-type-specific asynchronous modulation of PKA by dopamine in learning.
Cell-type-specific asynchronous modulation of PKA by dopamine in learning.
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DOI：
10.1038/s41586-020-03050-5
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Sabatini BL
中科院分区：
文献类型：
--
作者：
Lee SJ;Lodder B;Chen Y;Patriarchi T;Tian L;Sabatini BL
强化学习模型假设多巴胺（DA）释放神经元（DAN）编码有关动作和动作结果的信息，并以DA释放的形式向纹状体棘突投射神经元（SPN）提供教学信号。DA被认为是通过动态和差异调节蛋白激酶A（PKA）在每个类的SPN指导学习。然而，DA和SPN PKA之间的实时关系仍然没有在行为动物中进行测试。在这里，我们监测活动的DAN，细胞外DA水平，和净PKA活性的SPN在小鼠学习过程中的丘脑核。我们发现DA的正向和负向调制在整个训练过程中不断发展，这对于解释SPN PKA活性的同时波动是必要的和充分的。PKA在SPN中表达1型和2型DA受体的调节是二分的，使得它们分别对DA的增加和减少选择性敏感，这发生在学习的不同阶段。因此，PKA依赖的途径在每一类的SPN异步从事积极或消极的DA信号在学习过程中。
Reinforcement learning models postulate that dopamine (DA) releasing neurons (DANs) encode information about action and action outcome and provide a teaching signal to striatal spiny projection neurons (SPNs) in the form of DA release. DA is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of SPN. However, the real-time relationship between DA and SPN PKA remains untested in behaving animals. Here, we monitor the activity of DANs, extracellular DA levels, and net PKA activity in SPNs in the nucleus accumbens in mice during learning. We find positive and negative modulation of DA that evolves across training and is both necessary and sufficient to explain concurrent fluctuations in SPN PKA activity. The modulations of PKA in SPNs that express type-1 and type-2 DA receptors are dichotomous such that they are selectively sensitive to increases and decreases in DA, respectively, which occur at different phases of learning. Thus, PKA-dependent pathways in each class of SPNs are asynchronously engaged by positive or negative DA signals during learning.
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影响因子：
16.2
作者：
Chen Y;Granger AJ;Tran T;Saulnier JL;Kirkwood A;Sabatini BL
通讯作者：
Sabatini BL
神经元型特异性信号，用于腹侧对段区域的奖励和惩罚。
影响因子：
64.8
作者：
Cohen, Jeremiah Y.;Haesler, Sebastian;Vong, Linh;Lowell, Bradford B.;Uchida, Naoshige
通讯作者：
Uchida, Naoshige
影响因子：
5.3
作者：
Ilango, Anton;Kesner, Andrew J.;Ikemoto, Satoshi
通讯作者：
Ikemoto, Satoshi
影响因子：
64.8
作者：
Lee, Seok-Jin R.;Escobedo-Lozoya, Yasmin;Szatmari, Erzsebet M.;Yasuda, Ryohei
通讯作者：
Yasuda, Ryohei
影响因子：
5.4
作者：
Collins, Anne G. E.;Frank, Michael J.
通讯作者：
Frank, Michael J.