Dr. Yuji Naya: Differential coding of associative memory information in the macaque lateral prefrontal cortex and hippocampus

Abstract

The prefrontal cortex (PFC) and hippocampus (HPC) reportedly play crucial roles in the flexible use of stored information according to context. However, it remains unclear whether and how their neural representations differ during the context-guided retrieval. To solve this problem, we examined neural activity in the lateral PFC (lPFC, 470 neurons), medial PFC (mPFC, 322 neurons), and HPC (456 neurons) of two male macaques performing an item-location association memory task. The task required the animals to remember the location of a firstly-presented item-cue relative to a background image that was later shown with a tilt as a context-cue. Population-decoding analyses using all recorded neurons suggested that the lPFC and HPC (but not the mPFC) represented substantial task-related information. However, the represented contents differed between the two areas, both before and after the context-cue. Before the context-cue, the lPFC represented only the location retrieved from the item-cue, while the HPC also represented the item-cue itself. After the context-cue, the lPFC demonstrated a selective representation of the target-location regardless of the context-cue. In contrast, the HPC represented the three task-related pieces of information equivalently. These results suggest that the lPFC selectively represents goal-directed information at that moment among task-related information while the HPC automatically represents a task event and its mnemonically-linked information, implying complementary functional roles of the two brain regions as “regulator” and “supplier” in the context-guided memory process.

Significance statement Population decoding analysis of macaque single-unit data revealed neural representations in both the prefrontal cortex (PFC) and hippocampus (HPC), suggesting distinct and complementary roles in the flexible use of past memory within the current context. Previous studies have emphasized the goal-directed information represented by the HPC. However, the present study suggests that the HPC may simply sustain preceding events and associated memory traces regardless of task relevance, although some memory traces may correspond to goal-directed information. In contrast, the PFC, particularly the lateral PFC, selectively maintains goal-directed information. These findings depict neural operations of the HPC and PFC as “supplier” and “regulator” in the context-guided memory process.

Original Link: https://doi.org/10.1523/JNEUROSCI.0581-25.2026