Dobrott Courtney I, Becker Matthew I, Person Abigail L
bioRxiv. 2025 Aug 1:2025.08.01.668191. doi: 10.1101/2025.08.01.668191.
The ability to execute accurate movements is thought to rely on both anticipatory feedforward commands and rapid feedback corrections, yet how these control systems are integrated within cerebellar circuits remains unclear. Here, we show that corrective sub-movements (CSMs) - structured, feedback-driven adjustments occurring spontaneously during naturalistic mouse reaching - are not only encoded in anterior interposed (IntA) output neurons, but also act as instructive signals for feedforward learning. Closed-loop perturbations that trigger CSMs lead to learned shifts in the timing of future corrections, even in the absence of further perturbation. Strikingly, this learning depends on the timing of corrective responses, rather than the timing of the error itself, and is accompanied by physiological adaptation in cerebellar output neuronal firing rates. These findings reveal a cerebellar mechanism by which feedback responses train future anticipatory control signals, bridging the gap between reactive and anticipatory motor control in the cerebellum.
KEY FINDINGS/ HIGHLIGHTS: Mice generate rapid, precise corrective sub-movements (CSMs) during reach that counter both spontaneous variability and induced errorsCerebellar output neurons encode both predictive and corrective movements, mechanistically linking feedforward and feedback controlClosed-loop optogenetic disruption of cerebellar output induced reach errors that were entirely compensated by CSMsLearning was driven by the timing of corrective responses, not the timing of the initial error, suggesting an instructive role for CSMsBoth reach kinematics and cerebellar nuclear activity adapted over trials of repeated perturbationOptogenetic activation of cerebellar output drove errors and subsequent learning, but also blocked expression of that learning acutely, pinpointing cerebellar output as a key site of motor learning expressionFindings suggest a neural mechanism by which feedback corrections influence learning of feedforward control policies in cerebellar circuits.
执行精确动作的能力被认为依赖于预期的前馈指令和快速的反馈校正,然而这些控制系统如何在小脑回路中整合仍不清楚。在这里,我们表明,校正性子运动(CSMs)——在自然主义小鼠伸手过程中自发出现的、由反馈驱动的结构化调整——不仅在前间位核(IntA)输出神经元中编码,而且作为前馈学习的指导信号。触发CSMs的闭环扰动会导致未来校正时间的学习性偏移,即使在没有进一步扰动的情况下也是如此。引人注目的是,这种学习取决于校正反应的时间,而不是误差本身的时间,并且伴随着小脑输出神经元放电率的生理适应性变化。这些发现揭示了一种小脑机制,通过该机制反馈反应训练未来的预期控制信号,弥合了小脑反应性和预期性运动控制之间的差距。
关键发现/亮点:小鼠在伸手过程中产生快速、精确的校正性子运动(CSMs),以抵消自发变异性和诱发误差
小脑输出神经元对预测性和校正性运动进行编码,从机制上连接前馈和反馈控制
小脑输出的闭环光遗传学破坏诱发了伸手误差,这些误差完全由CSMs补偿
学习由校正反应的时间驱动,而不是初始误差的时间,表明CSMs具有指导作用
在重复扰动试验中,伸手运动学和小脑核活动均发生适应性变化
小脑输出的光遗传学激活引发误差和随后的学习,但也急性阻断了该学习的表达,确定小脑输出是运动学习表达的关键部位
研究结果表明存在一种神经机制,通过该机制反馈校正影响小脑回路中前馈控制策略的学习。