Unable to carry signals based on sights and sounds to the genes that record memories, a broken shuttle protein may hinder learning in patients with intellectual disability, schizophrenia and autism. This is the implication of a study led by researchers at Zhejiang University School of Medicine and NYU School of Medicine, which is published online June 22th in Nature Communications.

Specifically, the research team found that mice genetically engineered to lack the gene for the gCaMKII shuttle protein took twice as long as normal mice to form a memory needed to complete a simple task. This is the first study that showsgCaMKII plays a critical role in learning and memory in live animals. Adding more weight to their results, they showed that making the same change in the shuttle’s structure seen in a human child with severe intellectual disability also took away the ability of mice to learn. Importantly, the research team then restored the learning ability by re-inserting the human version of the shuttle protein into mice.

Going into the study, a “missing link” in the field was an understanding of how synapses “talk to” nerve cell nuclei as memories form.In the current study, researchers determined for the first time that this communication occurs when gCaMKII shuttles the calcium/calmodulin complexes that form just inside of nerve cells to their nuclei.Comparing spatial memory in mice without gCaMKII against normal mice, the authors found that gCaMKII “knockout” mice were much less able to locate a platform hidden beneath the surface of murky water in a maze. During this exercise, normal mice quickly identify the platform’s location. The team also found that, an hour after maze training, normal mice displayed a significant increase in expression of three genes – BDNF, c-Fos and Arc – known from past studies to help form long-term, spatial memories based on experiences. In contrast, training-induced increases in the expression of these genes did not occur in mice engineered to lack gCaMKII.

This work was supported by research grants to H.M. (the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities of China, 111 project, and the K. C. Wong Education Foundation) 

(Source: Huan MA’s Group, School of Basic Medical Sciences)