An image from the Allen Brain Atlas shows enriched expression of Kibra in the dentate gyrus and CA1 region of the hippocampus.
Why are memories like misty watercolors for some and crystal clear for others? Approximately 50% of the variability in human memory is due to genetic factors, but researchers have yet to identify genes that cause population-wide variation in memory. Now Papassotiropoulos et al. report a polymorphism that associates with improved memory performance in people in a recent article in Science.
The authors screened the DNA of people with differential performance in a memory task. They showed 30 unrelated words to 351 Swiss subjects and tested verbal memory 5 minutes and 24 hours later. They pooled DNA samples of people with similar memory performance and screened for more than 500,000 single-nucleotide polymorphisms (SNPs). The authors identified a SNP in the ninth intron of the KIBRA gene that associated with memory performance. KIBRA binds to dendrin, which is located in dendrites and regulates the actin cytoskeleton, and contains an interacting domain for protein kinase C zeta, which is important in long-term potentiation and memory. Relative to people with a cytosine (C) at the KIBRA SNP, people with a thymine (T) recalled words 24% better at 5 minutes and 19% better at 24 hours after seeing the word list. In contrast, people with the C and T alleles showed similar word recall immediately after training, suggesting that the KIBRA SNP associates with memory, not rehearsal or attention. The authors validated their findings in a similar Swiss cohort with 424 participants and an American cohort with 256 participants.
KIBRA expression localized to brain structures important in memory. In the human brain, the authors detected mRNA and protein for a truncated form of KIBRA that retains the memory-associated SNP. KIBRA expression localized to structures associated with memory, including the hippocampus and temporal and parietal lobes. The authors consulted the Allen Brain Atlas, which showed enriched expression of truncated Kibra in the dentate gyrus and CA1 region of the hippocampus in the mouse.
Functional magnetic resonance imaging showed increased activation in brains of people without relative to those with the T allele. The authors compared people with different genotypes who performed similarly in the verbal memory tests. During the retrieval of previously formed associations, people without the T allele showed increased activation of the right hippocampus and inferior parietal cortex and both medial frontal gyri relative to those with the T allele, suggesting that the brains of people lacking the T allele work harder to perform as well as those with the T allele, according to the authors. In contrast, people with and without the T allele showed similar brain activation during working memory tasks.
These data indicate that KIBRA is important in at least some types of human memory, raising the interesting possibility that memory disorders, including amnesia and learning disorders, might someday be treated by gene therapy.