BDNF polymorphism rs6265 and hippocampal structure and memory performance in healthy control subjects.

Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus of many species, including humans. The single-nucleotide polymorphism rs6265 on the BDNF gene is thought to alter activity-dependent secretion of the protein, and previous research suggests that the Met allele is associated with smaller hippocampal volumes and poorer memory performance in human populations. For this study, we genotyped 154 healthy human subjects for the Val66Met polymorphism. The effects of genotype upon hippocampal volume, as assessed using high resolution magnetic resonance imaging and high-dimensional brain mapping, and upon memory performance, as assessed using a battery of neuropsychological tests, were determined. We found that genotype had no significant effect on hippocampal structure, nor did it have a significant effect on memory performance, covarying for age. Age, however, was significantly related to changes in whole brain volume and performance on memory tasks. We concluded that in a large cohort of healthy human subjects, the Met allele of rs6265 is not associated with hippocampal structure or memory performance.

Individual differences in the expression of a "general" learning ability in mice.

Human performance on diverse tests of intellect are impacted by a "general" regulatory factor that accounts for up to 50% of the variance between individuals on intelligence tests. Neurobiological determinants of general cognitive abilities are essentially unknown, owing in part to the paucity of animal research wherein neurobiological analyses are possible. We report a methodology with which we have assessed individual differences in the general learning abilities of laboratory mice. Abilities of mice on tests of associative fear conditioning, operant avoidance, path integration, discrimination, and spatial navigation were assessed. Tasks were designed so that each made unique sensory, motor, motivational, and information processing demands on the animals. A sample of 56 genetically diverse outbred mice (CD-1) was used to assess individuals' acquisition on each task. Indicative of a common source of variance, positive correlations were found between individuals' performance on all tasks. When tested on multiple test batteries, the overall performance ranks of individuals were found to be highly reliable and were "normally" distributed. Factor analysis of learning performance variables determined that a single factor accounted for 38% of the total variance across animals. Animals' levels of native activity and body weights accounted for little of the variability in learning, although animals' propensity for exploration loaded strongly (and was positively correlated) with learning abilities. These results indicate that diverse learning abilities of laboratory mice are influenced by a common source of variance and, moreover, that the general learning abilities of individual mice can be specified relative to a sample of peers.