Accurate and precise timing is crucial for complex and purposeful behaviors, such as foraging for food or playing a musical instrument. The brain is capable of processing temporal information in a coordinated manner, as if it contains an ‘internal clock’. Similar to the need for the brain to orient itself in space in order to understand its surroundings, temporal orientation and tracking is an essential component of cognition as well. While there have been multiple models explaining the neural correlates of timing, independent lines of research appear to converge on the conclusion that populations of neurons in the dorsal striatum encode information relating to where a subject is in time relative to an anticipated goal. Similar to other learning processes, acquisition and maintenance of this temporal information is dependent on synaptic plasticity. Microtubules are cytoskeletal proteins that have been implicated in synaptic plasticity mechanisms and therefore are considered key elements in learning and memory. In this study, we investigated the role of microtubule dynamics in temporal learning by local infusions of microtubule stabilizing and destabilizing agents into the dorsolateral striatum. Our results suggested a bidirectional role for microtubules in timing, such that microtubule stabilization improves the maintenance of learned target durations, but impairs the acquisition of a novel duration. On the other hand, microtubule destabilization enhances the acquisition of novel target durations, while compromising the maintenance of previously learned durations. These findings suggest that microtubule dynamics plays an important role in synaptic plasticity mechanisms in the dorsolateral striatum, which in turn modulates temporal learning and time perception.

准确和精确的时间对于复杂和有目的的行为至关重要，例如觅食或演奏乐器。大脑能够以协调的方式处理时间信息，就好像它包含一个“内部时钟”。类似于大脑需要在空间中定位自己以了解其周围环境，时间定位和跟踪也是认知的重要组成部分。虽然有多种模型解释了时间的神经相关性，但独立的研究路线似乎都得出这样的结论，即背侧纹状体中的神经元群编码的信息与受试者相对于预期目标的时间位置有关。与其他学习过程类似，这种时间信息的获取和维护依赖于突触可塑性。微管是与突触可塑性机制有关的细胞骨架蛋白，因此被认为是学习和记忆的关键要素。在这项研究中，我们通过将微管稳定剂和去稳定剂局部注入背外侧纹状体来研究微管动力学在时间学习中的作用。我们的研究结果表明微管在时间上的双向作用，使得微管稳定改善了学习目标持续时间的维持，但损害了新持续时间的获得。另一方面，微管不稳定增强了新目标持续时间的获取，同时损害了先前学习持续时间的维持。