Ohtake Makoto, Abe Kenta, Hasegawa Masashi, Itokazu Takahide, Selvakumar Vihashini, Matunis Ashley, Stacy Emma, Froeblich Emily, Huynh Nathan, Lee Haesuk, Kambe Yuki, Yamamoto Tetsuya, Sato Tatsuo K, Sato Takashi R
Medical University of South Carolina, Department of Neuroscience, Charleston, South Carolina, United States.
Yokohama City University, Department of Neurosurgery, Yokohama, Japan.
Neurophotonics. 2024 Jul;11(3):033408. doi: 10.1117/1.NPh.11.3.033408. Epub 2024 May 9.
The initiation of goal-directed actions is a complex process involving the medial prefrontal cortex and dopaminergic inputs through the mesocortical pathway. However, it is unclear what information the mesocortical pathway conveys and how it impacts action initiation. In this study, we unveiled the indispensable role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions.
To investigate the role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions.
We designed a lever-press task in which mice internally determine the timing of the press, receiving a larger reward for longer waiting periods.
Our study revealed that self-initiated actions depend on dopaminergic signaling mediated by D2 receptors, whereas sensory-triggered lever-press actions do not involve D2 signaling. Microprism-mediated two-photon calcium imaging further demonstrated ramping activity in mesocortical axon terminals approximately 0.5 s before the self-initiated lever press. Remarkably, the ramping patterns remained consistent whether the mice responded to cues immediately for a smaller reward or held their response for a larger reward.
We conclude that mesocortical dopamine axon terminals encode the timing of self-initiated actions, shedding light on a crucial aspect of the intricate neural mechanisms governing goal-directed behavior.
目标导向行动的启动是一个复杂的过程，涉及内侧前额叶皮层和通过中皮层通路的多巴胺能输入。然而，尚不清楚中皮层通路传递何种信息以及它如何影响行动启动。在本研究中，我们揭示了中皮层轴突终末在编码自发行动中运动执行方面的不可或缺的作用。
研究中皮层轴突终末在编码自发行动中运动执行方面的作用。
我们设计了一种杠杆按压任务，其中小鼠自行决定按压的时机，等待时间越长获得的奖励越大。
我们的研究表明，自发行动依赖于由D2受体介导的多巴胺能信号传导，而感觉触发的杠杆按压行动不涉及D2信号传导。微棱镜介导的双光子钙成像进一步证明，在自发杠杆按压前约0.5秒，中皮层轴突终末出现斜坡状活动。值得注意的是，无论小鼠是立即对提示做出反应以获得较小奖励，还是延迟反应以获得较大奖励，斜坡状模式都保持一致。
我们得出结论，中皮层多巴胺轴突终末编码自发行动的时机，这为控制目标导向行为的复杂神经机制的一个关键方面提供了线索。
