小柯机器人

研究揭示多巴胺在学习过程中的功能
2020-12-25 14:59

美国哈佛医学院霍华德休斯医学研究所Bernardo L. Sabatini小组研发现在学习过程中多巴胺可异步调控细胞类型特异的蛋白激酶A(PKA)。相关论文于2020年12月23日在线发表于国际学术刊《自然》杂志。

在本研究中,研究人员在小鼠学习过程中监测了其伏隔核棘突投射神经元中释放多巴胺的神经元的活性、多巴胺细胞外水平和PKA活性。研究发现多巴胺的正向和负向调控在整个训练过程中不断发展,既有必要也足以解释棘突投射神经元中PKA活性的波动。表达1型和2型多巴胺受体的棘突投射神经元中PKA的调节是不同的,因此这些神经元分别对在不同阶段学习过程中发生的多巴胺增加和减少敏感。因此,在学习过程中,棘突投射神经元中PKA依赖性途径都受多巴胺正向或负向信号的异步调控。

据了解,强化学习模型认为释放多巴胺的神经元编码与行为和行为结果有关的信息,并以释放多巴胺的形式向纹状体棘突神经元提供学习信号。人们认为多巴胺通过动态和差异调控棘突投射神经元中的PKA来指导学习。但是,尚不清楚在动物行为发生过程中多巴胺和PKA在棘突投射神经元之间的实时关系。

Title: Cell-type-specific asynchronous modulation of PKA by dopamine in learning

Author: Suk Joon Lee, Bart Lodder, Yao Chen, Tommaso Patriarchi, Lin Tian, Bernardo L. Sabatini

Issue&Volume: 2020-12-23

Abstract: Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release1. Dopamine is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of spiny projection neuron2. However, the real-time relationship between dopamine and PKA in spiny projection neurons remains untested in behaving animals. Here we monitor the activity of dopamine-releasing neurons, extracellular levels of dopamine and net PKA activity in spiny projection neurons in the nucleus accumbens of mice during learning. We find positive and negative modulation of dopamine that evolves across training and is both necessary and sufficient to explain concurrent fluctuations in the PKA activity of spiny projection neurons. Modulations of PKA in spiny projection neurons that express type-1 and type-2 dopamine receptors are dichotomous, such that these neurons are selectively sensitive to increases and decreases, respectively, in dopamine that occur at different phases of learning. Thus, PKA-dependent pathways in each class of spiny projection neuron are asynchronously engaged by positive or negative dopamine signals during learning. The net PKA activities in each class of spiny projection neuron in the nucleus accumbens of the mouse are dichotomously modulated by asynchronous positive and negative dopamine signals during different phases of learning.

DOI: 10.1038/s41586-020-03050-5

Source: https://www.nature.com/articles/s41586-020-03050-5

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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