Working memory is capacity-limited. In everyday life we rarely notice this limitation, in part because we develop behavioral strategies that help mitigate the capacity limitation. How behavioral strategies are mediated at the neural level is unclear, but a likely locus is lateral prefrontal cortex (LPFC). Neurons in LPFC play a prominent role in working memory and have been shown to encode behavioral strategies. To examine the role of LPFC in overcoming working-memory limitations, we recorded the activity of LPFC neurons in animals trained to perform a serial self-ordered search task. This task measured the ability to prospectively plan the selection of unchosen spatial search targets while retrospectively tracking which targets were previously visited. We found that individual LPFC neurons encoded the spatial location of the current search target but also encoded the spatial location of targets up to several steps away in the search sequence. Neurons were more likely to encode prospective than retrospective targets. When subjects used a behavioral strategy of stereotyped target selection, mitigating the working-memory requirements of the task, not only did the number of selection errors decrease but there was a significant reduction in the strength of spatial encoding in LFPC. These results show that LPFC neurons have spatiotemporal mnemonic fields, in that their firing rates are modulated both by the spatial location of future selection behaviors and the temporal organization of that behavior. Furthermore, the strength of this tuning can be dynamically modulated by the demands of the task.
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