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19/09/2017 | Proc Natl Acad Sci U S A   IF 9.5
Temporal binding function of dorsal CA1 is critical for declarative memory formation.
Sellami A, Al Abed AS, Brayda-Bruno L, Etchamendy N, Valerio S, Oule M, Pantaleon L, Lamothe V, Potier M, Bernard K, Jabourian M, Herry C, Mons N, Piazza PV, Eichenbaum H, Marighetto A

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.

Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent 'spatial' navigation, which relies on knowledge of the relationship between landmarks in one's environment to build a cognitive map, and habit-based 'response' learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where 'Met' carriers use a response strategy more frequently than individuals homozygous for the 'Val' allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour.

2007 | Hippocampus   IF 4
Spontaneous navigational strategies and performance in the virtual town.
Etchamendy N, Bohbot VD

The 4-on-8 virtual maze provides evidence for variability in spontaneous strategy use during navigation. Functional magnetic resonance imaging (MRI) confirmed that these spatial and response strategies rely on the hippocampus and caudate nucleus memory systems, respectively. We asked whether the spontaneous use of a particular navigational strategy was associated with a particular ability to navigate in one's environment. We tested 30 young participants on the 4-on-8 virtual maze and we assessed their way finding ability in a virtual town. As expected, spatial learners performed well in the virtual town and the response learners, who never used external landmarks and relied purely on an egocentric strategy, performed poorly. Interestingly, a group who used the most efficient response strategy based on external landmarks in the 4-on-8 virtual maze, switched to the most efficient spatial strategy in the virtual town. Our data suggest that the best navigators are those who appropriately use spatial or response strategies depending on the demands of the task.