Suppressing unwanted memories by executive control

Freud proposed that unwanted memories can be forgotten by pushing them into the unconscious, a process called repression. The existence of repression has remained controversial for more than a century, in part because of its strong coupling with trauma, and the ethical and practical difficulties of studying such processes in controlled experiments. However, behavioural and neurobiological research on memory and attention shows that people have executive control processes directed at minimizing perceptual distraction, overcoming interference during short and long-term memory tasks and stopping strong habitual responses to stimuli. Here we show that these mechanisms can be recruited to prevent unwanted declarative memories from entering awareness, and that this cognitive act has enduring consequences for the rejected memories. When people encounter cues that remind them of an unwanted memory and they consistently try to prevent awareness of it, the later recall of the rejected memory becomes more difficult. The forgetting increases with the number of times the memory is avoided, resists incentives for accurate recall and is caused by processes that suppress the memory itself. These results show that executive control processes not uniquely tied to trauma may provide a viable model for repression.     

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.     

Charting a course for genomic medicine from base pairs to bedside

There has been much progress in genomics in the ten years since a draft sequence of the human genome was published. Opportunities for understanding health and disease are now unprecedented, as advances in genomics are harnessed to obtain robust foundational knowledge about the structure and function of the human genome and about the genetic contributions to human health and disease. Here we articulate a 2011 vision for the future of genomics research and describe the path towards an era of genomic medicine.     

Neural control of the forms of acetylcholinesterase in slow mammalian muscles

The 'heavy', collagen-tailed form of acetylcholinesterase (AChE), having a s(0)20,w of 16S in mammals, occurs at vertebrate muscle endplates and has been widely regarded as a marker of neuronal influence on muscle in vivo. However, an interesting exception has been described by Bacou et al., in a previous report in Nature. They found, in a slow-twitch muscle of the rabbit, that after denervation the 16S form of AChE increases markedly, rather than disappearing. Such a phenomenon would modify current concepts of neuromuscular regulation. We report here, however, that this exception is apparent rather than real in terms of endplate AChE regulation.