Post-encoding modulation of spatial memory by a GABA_A-agonist

Abstract

We investigated the role of the post-encoding period for consolidation of self-centered (egocentric) and world-centered (allocentric) spatial memory in neurologically normal human subjects. We used the GABAA-ergic anesthetic propofol to transiently modulate neural activity during the early stage of spatial memory consolidation. A total of 52 patients undergoing minor surgery learned to navigate to a target in a five-armed maze derived from animal experiments immediately prior to injection of propofol (early group) or more than 60 minutes before injection (late group). Two hundred and forty minutes after anesthesia, subjects were tested for memory-guided navigation. Our results show a selective impairment of memory-guided navigation in the early group and near-normal performance in the late group. Both egocentric and allocentric navigation were affected, albeit with distinct error patterns. In the egocentric condition, early group patients navigated significantly more often to a wrong alley of the maze but showed normal navigation times, thus suggesting a deficit mainly for memory of sequences of path segments. By contrast, in the allocentric condition, early group patients mostly navigated to the correct alley of the maze but showed a significant increase in detours and prolonged navigation times, thus suggesting a weakened representation of the relationship between landmarks. We conclude that presumably hippocampus-dependent networks contribute to early consolidation of representations underlying both egocentric and allocentric memory-guided navigation. Distinct aspects of these representations are susceptible to GABAA-ergic modulation within a post-encoding time-window of less than 60 minutes, indicating a redistribution and reconfiguration of spatial memory networks early during consolidation.

A Cognitive-Motor Framework for Spatial Navigation in Aging and Alzheimer’s Disease

“…One possible interpretation of our findings is that older adults place a greater reliance on complementary sensory cues to compensate for reduced acuity in other sensory domains. We note that this interpretation converges with recent findings that show patients with hippocampal lesions perform similarly to heathy controls in a virtual MWM environment when multisensory cues are available to aid navigation (Iggena et al, 2023;McAvan et al, 2022). An equally plausible, though not mutually exclusive possibility is that older adults benefit from having naturalistic walking cues available during navigation, which may compensate for difficulties associated with using a keyboard or joystick to navigate a virtual desktop environment.…”

Translating spatial navigation evaluation from experimental to clinical settings - the virtual environments navigation assessment (VIENNA)

“…This indicates that using online available spatial information in dynamic and unfamiliar environments successfully reduced the load on episodic memory in this task. Indeed, this distinction between episodic memory and navigation is also supported by studies reporting patients with profound hippocampal damage that show severe episodic memory deficits but intact navigation performance, when vestibular and proprioceptive cues can be used (Iggena et al, 2022;McAvan et al, 2022) or when maps are provided (Urgolites et al, 2016).…”

“…In these tasks, the extent to which participants need to supplement online available spatial representations (i.e., currently available cues like one's orientation on a route) with offline spatial representations (i.e., information on the route or environment which need to be recalled like a memorized map) (Wolbers & Hegarty, 2010) affects the extent of episodic memory recruitment. In recent patient lesion studies evidence for a dissociation between memory requirements and navigation emerged with memory-impaired patients exhibiting intact navigation performance (Iggena et al, 2022;McAvan, Wank, Rapcsak, Grilli, & Ekstrom, 2022;Urgolites, Kim, Hopkins, & Squire, 2016).…”