Iggena D, Maier PM, Häussler SM, Menk M, Olze H, Larkum ME, Finke C, Ploner CJ

Memory consolidation is a continuous transformative process between encoding and retrieval of mental representations. Recent research has shown that neural activity immediately after encoding is particularly associated with later successful retrieval. It is currently unclear whether post-encoding neural activity makes a distinct and causal contribution to memory consolidation. Here, we investigated the role of the post-encoding period for consolidation of spatial memory in neurologically normal human subjects. We used the GABA_A-ergic anesthetic propofol to transiently manipulate neural activity during the initial stage of spatial memory consolidation without affecting encoding or retrieval. A total of 52 participants undergoing minor surgery learned to navigate to a target in a five-armed maze derived from animal experiments. Participants completed learning either immediately prior to injection of propofol (early group) or more than 60 min before injection (late group). Four hours after anesthesia, participants were tested for memory-guided navigation. Our results show a selective impairment of navigation in the early group and near-normal performance in the late group. Analysis of navigational error patterns further suggested that propofol impaired distinct aspects of spatial representations, in particular sequences of path segments and spatial relationships between landmarks. We conclude that neural activity during the post-encoding period makes a causal and specific contribution to consolidation of representations underlying self-centered and world-centered memory-guided navigation. Distinct aspects of these representations are susceptible to GABA_A-ergic modulation within a post-encoding time-window of less than 60 min, presumably reflecting associative processes that contribute to the formation of integrated spatial representations that guide future behavior.

Cortex (2022)