Endocannabinoid signaling from 2-arachidonoylglycerol to CB1 cannabinoid receptor facilitates reward-based learning of motor sequence.
Endocannabinoid signaling from 2-arachidonoylglycerol to CB1 cannabinoid receptor facilitates reward-based learning of motor sequence.
复制标题
从 2-花生四烯酰甘油到 CB1 大麻素受体的内源性大麻素信号传导有助于基于奖励的运动序列学习。
DOI：
10.1016/j.neuroscience.2019.09.040
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发表时间：
2019
期刊：
影响因子：
3.3
通讯作者：
Ohno-Shosaku T
中科院分区：
文献类型：
--
作者：
Tanigami H;Yoneda M;Tabata Y;Echigo R;Kikuchi Y;Yamazaki M;Kishimoto Y;Sakimura K;Kano M;Ohno-Shosaku T
内源性大麻素系统调节突触传递，控制神经元兴奋性，并参与各种脑功能，包括学习和记忆。2-花生四烯酰甘油（2-arachidonoylglycerol，2-arachidonoylglycerol）是由二酰基甘油脂肪酶-α（diacylglycerol lipase-α，DGLα）产生的一种主要的内源性大麻素，由突触后神经元释放，逆行激活突触前CB 1大麻素受体，诱导短时程或长时程突触可塑性。为了研究内源性大麻素系统是否以及如何促进基于奖励的运动序列学习，我们对雄性CB 1敲除（KO）和DGLα-KO小鼠进行了三种类型的操作性按压任务。首先，我们训练小鼠按下标记为A、B和C的三个杠杆中的一个以获得食物奖励（单杠杆任务）。其次，我们训练小鼠按A、B和C的顺序按下三个杠杆（三杠杆任务）。第三，杠杆的顺序颠倒为C、B和A（反向三杠杆任务）。我们发现，CB 1-KO小鼠和DGLα-KO小鼠在操作性应激任务中表现出基本相同的缺陷。在单杠杆任务中，两种基因敲除小鼠都表现出学习按下杠杆获取食物的速度较慢。在三杠杆任务中，两种基因敲除小鼠的运动序列学习速度都较慢。在反向三杠杆任务中，两种基因敲除小鼠都需要更多的杠杆按压来进行反向学习。这些结果表明，内源性大麻素系统通过赋予动物在策略之间切换的灵活性来促进基于奖励的运动序列学习。
The endocannabinoid system modulates synaptic transmission, controls neuronal excitability, and is involved in various brain functions including learning and memory. 2-arachidonoylglycerol, a major endocannabinoid produced by diacylglycerol lipase-α (DGLα), is released from postsynaptic neurons, retrogradely activates presynaptic CB1 cannabinoid receptors, and induces short-term or long-term synaptic plasticity. To examine whether and how the endocannabinoid system contributes to reward-based learning of a motor sequence, we subjected male CB1-knockout (KO) and DGLα-KO mice to three types of operant lever-press tasks. First, we trained mice to press one of three levers labeled A, B, and C for a food reward (one-lever task). Second, we trained mice to press the three levers in the order of A, B, and C (three-lever task). Third, the order of the levers was reversed to C, B, and A (reverse three-lever task). We found that CB1-KO mice and DGLα-KO mice exhibited essentially the same deficits in the operant lever-press tasks. In the one-lever task, both strains of knockout mice showed a slower rate of learning to press a lever for food. In the three-lever task, both strains of knockout mice showed a slower rate of learning of the motor sequence. In the reverse three-lever task, both strains of knockout mice needed more lever presses for reversal learning. These results suggest that the endocannabinoid system facilitates reward-based learning of a motor sequence by conferring the flexibility with which animals can switch between strategies.