马克斯·普朗克佛罗里达神经科学研究所Hidehiko K. Inagaki团队宣布他们的研究开发出了皮质-基底神经节回路中灵活运动定时的积分器动力学。2025年11月19日出版的《自然》发表了这项成果。

为了解决这个问题，研究团队在执行灵活的舔定时任务的小鼠中进行了微扰实验，并结合了多区域电生理学。在额叶皮层短暂的沉默后，皮层和纹状体的活动迅速恢复到沉默前的水平，并恢复上升，导致舔食时间的变化接近沉默持续时间。相反，短暂抑制纹状体会导致两个区域的斜坡活动逐渐减少，斜坡从抑制后的水平恢复，将舔舐时间转移到抑制持续时间之外。它们分别抑制额叶皮质和纹状体有效地激活和倒回定时器。这些发现与一个模型相一致，在这个模型中，纹状体是一个网络的一部分，该网络暂时整合来自额叶皮层的输入，并产生调节运动时间的斜坡活动。

据悉，灵活控制电机的时间是至关重要的行为。在意志运动开始之前，额叶皮层和纹状体表现出斜坡式的尖峰活动，斜坡式的变化预示着运动的开始。皮质-基底神经节环路中的这种活动可能起着可调节的“计时器”的作用，在所需的时间触发动作。然而，由于额叶皮质和纹状体具有相似的斜坡动力学，并且都是计时行为所必需的，因此区分它们在计时器功能中的各自作用仍然具有挑战性。

附：英文原文

Title: Integrator dynamics in the cortico-basal ganglia loop for flexible motor timing

Author: Yang, Zidan, Inagaki, Miho, Gerfen, Charles R., Fontolan, Lorenzo, Inagaki, Hidehiko K.

Issue&Volume: 2025-11-19

Abstract: Flexible control of motor timing is crucial for behaviour1,2,3,4. Before volitional movement begins, the frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets5,6,7,8,9,10,11,12. This activity in the cortico-basal ganglia loop may function as an adjustable ‘timer,’ triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviours, distinguishing their individual roles in this timer function remains challenging. Here, to address this, we conducted perturbation experiments combined with multi-regional electrophysiology in mice performing a flexible lick-timing task. Following transient silencing of the frontal cortex, cortical and striatal activity swiftly returned to pre-silencing levels and resumed ramping, leading to a shift in lick timing close to the silencing duration. Conversely, briefly inhibiting the striatum caused a gradual decrease in ramping activity in both regions, with ramping resuming from post-inhibition levels, shifting lick timing beyond the inhibition duration. Thus, inhibiting the frontal cortex and striatum effectively paused and rewound the timer, respectively. These findings are consistent with a model in which the striatum is part of a network that temporally integrates input from the frontal cortex and generates ramping activity that regulates motor timing.

DOI: 10.1038/s41586-025-09778-2

Source: https://www.nature.com/articles/s41586-025-09778-2