期刊
NEUROSCIENCE
卷 421, 期 -, 页码 1-16出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2019.09.040
关键词
Endocannabinoid system; Lever press; Reinforcement learning; Reversal learning
资金
- Japan Society for the Promotion of Science [21220006, 23500466, 25000015, 16H04650, 16K01449, 17K19444, 18H04012]
- Grants-in-Aid for Scientific Research [16K01449, 23500466, 18H04012, 16H04650, 17K19444] Funding Source: KAKEN
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-alpha (DGL alpha), 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 DGL alpha-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 DGL alpha-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. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
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