Impaired Sequential Egocentric and Allocentric Memories in Forebrain-Specific–NMDA Receptor Knock-Out Mice during a New Task Dissociating Strategies of Navigation

Abstract

The hippocampus is considered to play a role in allocentric but not in egocentric spatial learning. How does this view fit with the emerging evidence that the hippocampus and possibly related cortical areas are necessary for episodic-like memory, i.e., in all situations in which events need to be spatially or sequentially organized? Are NMDA receptor-dependent mechanisms crucial for the acquisition of spatiotemporal relationships? To address this issue, we used knock-out (KO) mice lacking hippocampal CA1 NMDA receptors and presenting a reduction of these receptors in the deep cortical layers (NR1-KO mice). A new task (the starmaze) was designed, allowing us to distinguish allocentric and sequential-egocentric memories. NR1-KO mice were impaired in acquiring both types of memory. Our findings suggest that memories composed of multiple spatiotemporal events require intact NMDA receptors-dependent mechanisms in CA1 and possibly in the deep cortical layers.

Lateralized human hippocampal activity predicts navigation based on sequence or place memory

“…Left-lateralized hippocampal activation for sequential egocentric representations also supports the idea that the left hippocampus mediates spatiotemporal associations between the multiple events that constitute the elements of an episodic memory (2, 41). This finding is consistent with hippocampal involvement in sequential route-based navigation in rodents (14) and the planning of complex routes in human (15,42).…”

“…Similarly, navigation via a fixed route (15, 17) or relative to a single landmark (16), consistent with simple egocentric representations, has been associated with the dorsal striatum. However, to our knowledge, the neural bases of the sequential egocentric representation have not yet been identified in humans, and could provide a link between spatial navigation and episodic memory.Here we adapt the Starmaze task developed for mice (14,20) to investigate the neural bases of sequential egocentric representations and allocentric representations in humans. The task allows the parallel use of both types of representation during learning and performance of training trials, but also allows the use of one or other representation to be detected by the response made in probe trials.…”

“…Here we adapt the Starmaze task developed for mice (14,20) to investigate the neural bases of sequential egocentric representations and allocentric representations in humans. The task allows the parallel use of both types of representation during learning and performance of training trials, but also allows the use of one or other representation to be detected by the response made in probe trials.…”

“…Rondi-Reig et al (14) recently demonstrated that an additional sequential egocentric representation depends on the rodent hippocampus. The human hippocampus has likewise been associated with allocentric representations of location, allowing accurate navigation from new starting locations (15) based on the configuration of environmental cues (16,17) or recognition of locations from a new viewpoint (18,19).…”

Accumulated hippocampal formaldehyde induces age-dependent memory decline

“…It is known that NR1 and NR2B are both necessary for long-term memory formation (Nakazawa et al 2004), since knockout of either NR1 or NR2B induces cognitive deficits in mice (Clayton et al 2002;Rondi-Reig et al 2006). In our study, NR2B expression initially increased then decreased in cultured hippocampal neurons after treatment with different concentrations of formaldehyde in vitro ( Fig.…”