Molecular biosensor important for learning discovered

Although most people take for granted their brain’s ability to be learning almost constantly, a team of researchers has discovered the complex molecular cascade of events that happens at brain synapses – across which information from one neuron flows to another – when we learn and remember.

“We knew for quite some time that synaptic connections are physically changed when we learn something new,” explains Dr. Shernaz Bamji, researcher with the Djavad Mowafaghian Centre for Brain Health and associate professor at the University of British Columbia’s Life Sciences Institute, Faculty of Medicine. “What we did not know was how the learning event could translate into physical changes at the synapse. Now through our research we have an idea.”

Dr. Bamji and her research team published their findings in, “Palmitoylation of δ-catenin by DHHC5 mediates activity-induced synapse plasticity”, in Nature Neuroscience earlier this year.

The team discovered the biochemical modification of a protein in the brain called delta-catenin. Upon learning something new, this modification causes delta-catenin to get recruited to the membrane of the synapse and associate with adhesion molecules and stabilize those adhesions, thereby strengthening the synapse.

Delta-catenin function key to mental disability

Previous research demonstrated that animals lacking delta-catenin display severe disruptions in synapse plasticity as well as learning and memory. Delta-catenin mutations and deletion of the gene are very strongly linked with intellectual disability and a significant reduction of delta-catenin has been observed in the brains of patients with cri-du-chat syndrome.

“We now have a very good idea of exactly how delta-catenin is functioning in the brain to regulate learning and how deleting this gene may cause mental disability,” says Dr. Bamji.

“Delta-catenin and other molecules in the cadherin adhesion complex have been shown to be genetically linked to addiction disorders,” she says. “We want to find out if regulating the expression of the delta-catenin gene and its post-translational modification can either modify the acquisition of addiction memories or enhance the extinction of addiction memories.”

The study’s findings provide a potential target to correct some of the changes that occur in the brains of patients with memory loss, such as individuals with Alzheimer’s.

“We also want to better understand whether this particular post-translational modification truly is important in memory and cognitive function,” she adds. “Our goal is to investigate whether regulating the stabilization of some of these adhesion molecules at the synapse helps with cognitive function and flexibility.”