Department of Psychology and Neuroscience, Duke University, Durham, NC, United States.
Department of Psychology and Neuroscience, Duke University, Durham, NC, United States.
Neurobiol Learn Mem. 2021 Sep;183:107468. doi: 10.1016/j.nlm.2021.107468. Epub 2021 May 29.
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.
精确的时间把握对于复杂而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，就好像它内部有一个“时钟”一样。类似于大脑为了理解周围环境而需要在空间中定位自己一样，时间定向和跟踪也是认知的一个基本组成部分。虽然有多种模型解释了时间的神经相关性，但独立的研究似乎都得出了一个结论，即背侧纹状体中的神经元群体编码了与主体相对于预期目标的时间位置有关的信息。与其他学习过程类似，这种时间信息的获取和维持依赖于突触可塑性。微管是细胞骨架蛋白，与突触可塑性机制有关，因此被认为是学习和记忆的关键要素。在这项研究中，我们通过向背外侧纹状体局部输注微管稳定和不稳定剂来研究微管动力学在时间学习中的作用。我们的结果表明微管在时间上具有双向作用，即微管稳定可以改善学习目标持续时间的维持，但会损害新持续时间的获取。另一方面，微管去稳定化增强了对新目标持续时间的获取，同时损害了对以前学习过的持续时间的维持。这些发现表明，微管动力学在背外侧纹状体的突触可塑性机制中起着重要作用，进而调节时间学习和时间感知。
