The entorhinal-DG/CA3 pathway in the medial temporal lobe retains visual working memory of a simple surface feature.

Classic models consider working memory (WM) and long-term memory as distinct mental faculties that are supported by different neural mechanisms. Yet, there are significant parallels in the computation that both types of memory require. For instance, the representation of precise item-specific memory requires the separation of overlapping neural representations of similar information. This computation has been referred to as pattern separation, which can be mediated by the entorhinal-DG/CA3 pathway of the medial temporal lobe (MTL) in service of long-term episodic memory. However, although recent evidence has suggested that the MTL is involved in WM, the extent to which the entorhinal-DG/CA3 pathway supports precise item-specific WM has remained elusive. Here, we combine an established orientation WM task with high-resolution fMRI to test the hypothesis that the entorhinal-DG/CA3 pathway retains visual WM of a simple surface feature. Participants were retrospectively cued to retain one of the two studied orientation gratings during a brief delay period and then tried to reproduce the cued orientation as precisely as possible. By modeling the delay-period activity to reconstruct the retained WM content, we found that the anterior-lateral entorhinal cortex (aLEC) and the hippocampal DG/CA3 subfield both contain item-specific WM information that is associated with subsequent recall fidelity. Together, these results highlight the contribution of MTL circuitry to item-specific WM representation.