FIGURE 2.

Variation in working memory is heritable in early adulthood (6 months) and middle age (14 months) but is not significantly controlled by a single genetic locus. (A) We used the y-maze as a test of working memory in B6-BXD mice at both 6 months and 14 months. In this version of the y-maze test, we used visual cues placed outside of the maze and allowed the mouse to freely explore each arm. Entering each of the three arms in succession was considered a successful spontaneous alternation (“Spon Alt”). (B) Performance on the y-maze test is heritable (h²_RIx̄ = 0.51 at 6 months and 0.62 at 14 months). (C) Quantitative trait locus mapping indicated that no single genetic locus contributed significantly to performance on the y-maze at either age, suggesting that working memory is a polygenetic trait. (D) The relationship between each WGCNA module eigengene expression and cognitive function at 6 months was assessed using Pearson correlations. Significant correlations are represented by blue (positive correlation) or red (negative correlation) shading, with color intensity corresponding with correlation strength. Four WGCNA modules were associated with y-maze at 6 months: darkolivegreen, darkred, lightyellow, and saddlebrown. (E) Expression of the lightyellow module was significantly positively associated with working memory at 6 months (R = 0.57, p = 0.004); however, expression of the hub gene of this module Trio, was not significantly associated with working memory (R = −0.38, p = 0.07). (F) Two modules at 14 months were significantly correlated to performance on y-maze at 14 months: greenyellow and darkolivegreen. QTL significance thresholds: red line, alpha = 0.05; black line, alpha = 0.33.