GPR12 Plays Role in Working Memory

Working memory isn't neatly confined to one brain area, but requires the synchronous activity of at least two, and the involvement of GPR12 receptors, according to a study published today in Cell. 

"There were in fact hints from earlier research that multiple brain structures are somehow involved in working memory," says Priya Rajasethupathy, neuroscientist at Rockefeller University. "Our new findings give us more-tangible insights into what these areas are and how they are contributing."

The team explored how working memory functions among a special population of genetically diverse mice. They saw broad variations in the mice's performance, and a subsequent genetic analysis highlighted one place in the genome that could explain a considerable portion of that variability. The researchers found one gene with striking effects on the animals' working memory. By boosting its expression, they could turn a mouse from one who used to perform at chance level to one who gets it right 80 percent of the time—or create more forgetful mice by hampering the gene's expression.

The team then investigated how this gene affects the brain and behavior of mice, and found that these receptors are not in the prefrontal cortex, but in neurons in the brain's thalamus. High-performing mice had about three times as many of these receptors in their thalamus than low-performing mice. They found that the higher the synchrony, the more likely the mouse was to make an accurate left or right choice when coming into a fork in the maze.

"We demonstrate that mice that perform better, have more of these receptors and are therefore able to establish more synchrony," Rajasethupathy said. Rajasethupathy and her colleagues plan to continue investigating the details of the role played by GPR12 receptors—work which may lead to potential therapeutic targets for treating deficits in working memory.