A line of genetically modified mice that Western University scientists call “Forrest Gump” because, like the movie character, they can run far but they aren’t smart, is furthering the understanding of a key neurotransmitter called acetylcholine (ACh). Marco Prado, PhD, and his team at Robarts Research Institute say the mice show what happens when too much of this neurotransmitter becomes available in the brain. Boosting ACh is a therapeutic target for Alzheimer’s disease because it’s found in reduced amounts when there’s cognitive failure.

Prado’s research is published in the Journal of Neuroscience.

“We wanted to know what happens if you have more of the gene which controls how much acetylcholine is secreted by neurons,” says Prado, a Robarts scientist and professor in the Departments of Physiology and Pharmacology and Anatomy and Cell Biology at Western’s Schulich School of Medicine & Dentistry. “The response was the complete opposite of what we expected. It’s not a good thing. Acetylcholine release was increased threefold in these mice, which seemed to disturb cognitive function. But put them on a treadmill and they can run twice as far as normal mice before tiring. They’re super-athletes.” In addition to its function in modulating cognitive abilities, ACh drives muscle contraction which allowed for the marked improvement in motor endurance.

This is a mouse brain.

The researchers found the mice, which have the scientific name ChAT-ChR2-EYFP, had terrible attention spans, as well as dysfunction in working memory and spatial memory. The mouse brain image is used for illustrative purposes only.

One of the tests the scientists, including first author Benjamin Kolisnyk, used is called the touch screen test for mice (video is available showing the test) which uses technology similar to a tablet. After initiating the test, the mice have to scan five different spots on the touch screen to see a light flash, and then run and touch that area. If they get it right they get a reward. Compared to the control mice, the “Forrest Gump” mice failed miserably at the task. The researchers found the mice, which have the scientific name ChAT-ChR2-EYFP, had terrible attention spans, as well as dysfunction in working memory and spatial memory.

Prado interprets the research as showing ACh is very important for differentiating cues. So if your brain is presented with a lot of simultaneous information, it helps to pick what’s important. But when you flood the brain with ACh, your brain loses the ability to discern what’s relevant. This study was funded mainly by the Canadian Institutes of Health Research.

Notes about this neuroscience and acetylcholine research

Contact: Kathy Wallis – University of Western Ontario
Source: University of Western Ontario press release
Image Source: The mouse brain image is credited to the NIH and is in the public domain.
Original Research: Abstract for “ChAT–ChR2–EYFP Mice Have Enhanced Motor Endurance But Show Deficits in Attention and Several Additional Cognitive Domains” by Benjamin Kolisnyk, Monica S. Guzman, Sanda Raulic, Jue Fan, Ana C. Magalhães, Guoping Feng, Robert Gros, Vania F. Prado, and Marco A. M. Prado in Journal of Neuroscience. Published online June 19 2013 doi:10.1523/JNEUROSCI.0395-13.2013