The lateral prefrontal cortex (PFC) in humans and other primates is critical for immediate, goal-directed behaviour and working memory, which are classically considered distinct from the cognitive and neural circuits that support long-term learning and memory. Over the past few years, a reconsideration of this textbook perspective has emerged, in that different timescales of memory-guided behaviour are in constant interaction during the pursuit of immediate goals. Here, we will first detail how neural activity related to the shortest timescales of goal-directed behaviour (which requires maintenance of current states and goals in working memory) is sculpted by long-term knowledge and learning — that is, how the past informs present behaviour. Then, we will outline how learning across different timescales (from seconds to years) drives plasticity in the primate lateral PFC, from single neuron firing rates to mesoscale neuroimaging activity patterns. Finally, we will review how, over days and months of learning, dense local and long-range connectivity patterns in PFC facilitate longer-lasting changes in population activity by changing synaptic weights and recruiting additional neural resources to inform future behaviour. Our Review sheds light on how the machinery of plasticity in PFC circuits facilitates the integration of learned experiences across time to best guide adaptive behaviour.

人类和其他灵长类动物的外侧前额皮质 (PFC) 对于即时、目标导向的行为和工作记忆至关重要，传统上认为这与支持长期学习和记忆的认知和神经回路不同。在过去的几年里，人们对这一教科书观点进行了重新思考，即在追求眼前目标的过程中，记忆引导行为的不同时间尺度不断相互作用。在这里，我们将首先详细介绍与目标导向行为的最短时间尺度相关的神经活动（这需要维持工作记忆中的当前状态和目标）是如何通过长期知识和学习来塑造的——也就是说，过去如何影响现在行为。然后，我们将概述不同时间尺度（从几秒到几年）的学习如何驱动灵长类动物外侧 PFC 的可塑性，从单个神经元放电率到中尺度神经影像活动模式。最后，我们将回顾经过数天和数月的学习，PFC 中密集的局部和远程连接模式如何通过改变突触权重和招募额外的神经资源来告知未来的行为，从而促进群体活动的更持久的变化。我们的综述揭示了 PFC 电路中的可塑性机制如何促进跨时间的学习经验的整合，以最好地指导适应性行为。