Prefrontal Pyramidal Neurons are Critical for All Phases of Working Memory

Abstract

The prefrontal cortex (PFC) has long been known to be essential for working memory (WM), yet exactly how it contributes to this fundamental cognitive process remains incompletely understood. The PFC has primarily been viewed as being responsible for the maintenance of information over a delay, but it is unclear whether it also plays a more general role during WM. To address this, we performed task phase-specific optogenetic silencing of pyramidal neurons in the medial PFC (mPFC) of mice performing a spatial WM task. We found that the mPFC was required not only during the delay phase of the task but also during other phases requiring the encoding and retrieval of spatial information. To gain further insights into how WM is supported by mPFC pyramidal neurons, we imaged their activity during all phases of the task using head-mounted miniscopes. This revealed that neurons were active during all task phases and were most strongly influenced by the animals’ position and running direction, indicating a fundamental role in spatial navigation. Taken together, these results delineate the functional contribution of mPFC pyramidal neurons to WM, extending their role beyond the maintenance of information.