Researchers have found a new way to directly compare mental abilities in mice and humans to more accurately model impairments observed in neurological and psychiatric diseases.

Although rodents are often studied to investigate human disease, researchers just as frequently struggle to translate lab findings from rodents into real-world applications for people. This is particularly the case in modeling some of the complex cognitive disturbances observed in patients using animal models. In a paper published online October 1 in Scientific Reports, a research team reported a novel approach to help bridge that gap: a spatial memory test administered to both people and mice with a mutation in the same gene to show that it produces the same learning impairment.

The work, led by Jess Nithianantharajah, Ph.D., a 2013 NARSAD Young Investigator grantee currently based at the University of Melbourne, Australia, studied mice and humans with an inactive Dlg2 gene. Dlg2 is an important gene expressed at the connection between brain cells and is essential for how the brain processes information about the world. Mutations in this gene are rare in people but have been observed in individuals with schizophrenia, autism, intellectual disability and bipolar disorder. The mutations have also been linked to general cognitive ability.

The current work extends a past study by the same team, which looked at other members of genes closely related to Dlg2 and compared mice and humans on cognitive tasks using different sets of tests for mice vs. humans. Dr. Nithianantharajah’s team focused on Dlg2 to produce the first testing model that evaluates complex problem solving in mice and humans carrying the same genetic mutations associated with mental illness. In the current work, they have extended this to develop one test that can be used in both people and mice.

In the team’s experiments, mice and people had to track pictures of different objects in different locations on a touchscreen device. The mice gave their responses with nose-touch, and the human participants by finger touch. Both mice and people with inactive Dlg2 genes showed reduced learning on the touchscreen task, compared to control mice without the Dlg2 mutation, as well as study participants with normal Dlg2 gene expression. The findings support the test as a means of directly comparing cognitive processes between mice and humans — processes that are parallel in that they are disrupted by the same genetic mutations and apply to the same object-location activity.

Beyond this specific case, the researchers say, they hope their test can lead to better ways of modeling human cognitive impairments in animals, and in improving translation of insights obtained from these genetic mouse models from lab to clinic. The researchers also stress that having better disease models is crucial to push forward the growing body of studies seeking therapeutic targets for treating cognitive dysfunction in diseases.

Read the paper.