Hippocampal Neurogenesis Levels Predict WATERMAZE Search Strategies in the Aging Brain

Joana Gil-Mohapel,Russ Gothard,Patricia S Brocardo,Brian R Christie,Jessica M Simpson,Will Choquette,Mark P Mattson

doi:10.1371/journal.pone.0075125

Joana Gil-Mohapel, Russ Gothard + Show 5 more

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https://doi.org/10.1371/journal.pone.0075125

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Journal: PloS one	Publication Date: Sep 23, 2013
Citations: 205	License type: CC BY 4.0

Affiliation: University of Victoria, University of British Columbia

Abstract

The hippocampus plays a crucial role in the formation of spatial memories, and it is thought that adult hippocampal neurogenesis may participate in this form of learning. To better elucidate the relationship between neurogenesis and spatial learning, we examined both across the entire life span of mice. We found that cell proliferation, neuronal differentiation, and neurogenesis significantly decrease with age, and that there is an abrupt reduction in these processes early on, between 1.5-3 months of age. After this, the neurogenic capacity continues to decline steadily. The initial abrupt decline in adult neurogenesis was paralleled by a significant reduction in Morris Water Maze performance, however overall learning and memory remained constant thereafter. Further analysis of the search strategies employed revealed that reductions in neurogenesis in the aging brain were strongly correlated with the adoption of spatially imprecise search strategies. Overall, performance measures of learning and memory in the Morris Water Maze were maintained at relatively constant levels in aging animals due to an increase in the use of spatially imprecise search strategies.

Highlights

The ability to generate new neurons continues into adulthood in a few select regions of the mammalian brain, including the sub-ventricular zone (SVZ) and the sub-granular zone (SGZ) of the dentate gyrus (DG) of the hippocampus [1,2,3,4,5,6,7,8]
In order to further delineate the pattern of age-associated decrease in hippocampal proliferative capacity, we assayed DG cell proliferation in POMC-enhanced green fluorescent protein (EGFP)-expressing mice of the following ages: 1, 1.5, 2, 2.5, 3, 4, 6, 12, 18, and 24 months
We observed a progressive decrease in the expression of Ki-67 in the DG with age [one-factor analysis of variance (ANOVA), F(9, 68) = 55.43, p < 0.001] that was best fitted to a negative exponential curve [Y = 2733x e(-0.199X), with a correlation coefficient r2 = 0.85] (Figure 2 A-C)

Summary

Introduction

The ability to generate new neurons continues into adulthood in a few select regions of the mammalian brain, including the sub-ventricular zone (SVZ) and the sub-granular zone (SGZ) of the dentate gyrus (DG) of the hippocampus [1,2,3,4,5,6,7,8]. In the DG, newborn neurons must migrate a short distance from the SGZ to the granule cell layer (GCL) where they integrate into the existing circuitry [8,9]. The maturation of these neurons into functional units appears to occur over a period of four to five weeks following the initial mitotic event [9,10]. It is reasonable to speculate that these new neurons might be integral for hippocampal-dependent learning and memory [22,23]. In agreement with this hypothesis, numerous correlative studies have shown that hippocampal neurogenesis can be modulated by learning and behavioural experience [24,25,26,27], and that a loss in hippocampal neurogenic function can adversely affect memory formation [20,28,29,30,31]

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