Researchers have identified a gene involved in building the circuitry that relays signals through the brain, by using a powerful gene-hunting technique for the first time in mammalian brain cells.
The researchers said that the gene is a likely player in the aging process in the brain. Additionally, in demonstrating the usefulness of the new method, the discovery paves the way for faster progress toward identifying genes involved in complex mental illnesses such as autism and schizophrenia.
Lead author Richard Huganir, Ph.D., director of the Johns Hopkins University Solomon H. Snyder Department said by adapting an automated process to neurons, they were able to go through 800 genes to find one needed for forming synapses- connections- among those cells.
In this study, Huganir's group worked to test many genes all at once using plastic plates with dozens of small wells. A robot was used to add precise allotments of cells and nutrients to each well, along with molecules designed to knock out one of the cells' genes- a different one for each well.
The team used a trial-and-error approach, adjusting how often the nutrient solution was changed and adding a washing step, and eventually coaxed the cells to thrive in the wells. In addition,
The team screened 800 genes and found big differences in the well of cells with a gene called LRP6 knocked out. LRP6 had previously been identified as a player in a biochemical chain of events known as the Wnt pathway, which controls a range of processes in the brain.
The team found that LRP6 was only found on a specific kind of synapse known as an excitatory synapse, suggesting that it enables the Wnt pathway to tailor its effects to just one synapse type.
The study was published in Cell Reports.