Self-directed exploration provides a Ncs1-dependent learning bonus.

Scientific reports (2015-12-08)
Ho-Suk Mun, Bechara J Saab, Enoch Ng, Alexander McGirr, Tatiana V Lipina, Yoichi Gondo, John Georgiou, John C Roder
ABSTRACT

Understanding the mechanisms of memory formation is fundamental to establishing optimal educational practices and restoring cognitive function in brain disease. Here, we show for the first time in a non-primate species, that spatial learning receives a special bonus from self-directed exploration. In contrast, when exploration is escape-oriented, or when the full repertoire of exploratory behaviors is reduced, no learning bonus occurs. These findings permitted the first molecular and cellular examinations into the coupling of exploration to learning. We found elevated expression of neuronal calcium sensor 1 (Ncs1) and dopamine type-2 receptors upon self-directed exploration, in concert with increased neuronal activity in the hippocampal dentate gyrus and area CA3, as well as the nucleus accumbens. We probed further into the learning bonus by developing a point mutant mouse (Ncs1(P144S/P144S)) harboring a destabilized NCS-1 protein, and found this line lacked the equivalent self-directed exploration learning bonus. Acute knock-down of Ncs1 in the hippocampus also decoupled exploration from efficient learning. These results are potentially relevant for augmenting learning and memory in health and disease, and provide the basis for further molecular and circuit analyses in this direction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting mouse Dlc1
Sigma-Aldrich
MISSION® esiRNA, targeting human DLC1
Sigma-Aldrich
MISSION® esiRNA, targeting human HP

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