A recent experiment conducted by scientists at Southwestern Medical Center succeeded in genetically engineering mice that were notably more intelligent than their cousins by removing an enzyme in their brain. It caused them to learn more quickly and to notice that their environment had been altered, the researchers say. Published in the journal Nature Neuroscience, the scientists believe the discovery may lead to more advanced and effective treatments for devastating neurodegenerative diseases like Alzheimer’s disease. According to the senior author and assistant professor of psychiatry, Dr. James Bibb, “It’s pretty rare that you make mice ‘smarter,’ so there are a lot of cognitive implications…Everything is more meaningful to these mice,” he said. “The increase in sensitivity to their surroundings seems to have made them smarter.”
The mice exhibited higher levels of intelligence on numerous standard intelligence tests for mice. They were better at navigating a maze and also quicker to remember unpleasant stimuli, such as a box that delivered an uncomfortable shock to the mice. Likewise, when the enivronment was altered, the mice quickly figured out how to navigate the new route. The long-term effects of removing this enzyme, known as Cdk5, from the brains of mice, however, are still unknown, and the appropriateness of some form of parallel therapy in humans is therefore tentative and still very much in the preliminary stages. The researchers are particularly interested in developing drugs which may mimic the intelligent-enhancing effects of removing the enzyme, thereby eliminating the need for genetic therapy in humans.
The enzyme Cdk5 has also been implicated in studies of the neurobiological and genetic correlates of drug abuse. In their experiment, the researchers knocked out the gene, but only in the brain, and they waited until the mice had reached adulthood, taking advantage of a relatively recent technological advanced known as ‘conditional knockout.’ This new technology has allowed for unprecedented sophistication in experimentation, according to Dr. Bibbb: “Being able to turn a gene off throughout a brain is a really advanced thing to do…It’s been shown that it can be done, but we put the system together and actually applied it.”
But how does removing this gene from the brains of mice produce its remarkable effects? Cdk5 interacts with a molecule called NR2B, which is involved in stimulating cells to fire when a neurotransmitter is bound to it. It is found in nerve-cell membranes, and scientists believe that NR2B is instrumental in early learning. Removing Cdk5 from the brain causes NR2B levels to radically increase, enhancing the brainpower of the mice. The scientists tested the response of slices of the hippocampus from the brains of the mice with electrical stimulation, and found these pieces of the brain much more responsive. This, the researchers say, is further evidence of the enhanced intelligence of the mice.
The experiment follows another similar one, in which researchers from MIT and Washington University provided mice with extra copies of the NR2B gene, in addition to engineering these copies to increase with age. The mice were not only notably more intelligent, but were resistant to the effects of aging, suggesting that scientists may have discovered a potentially helpful route in treating neurodegenerative disorders. Like the mice in the aforementioned experiment, these mice exhibited a much greater capacity for memory. They recognized objects for several more days than other mice did, and also exhibited a greater degree of curiosity in exploring new objects. Like the mice in the other experiment, these mice were better at remembering and avoiding previously experienced aversive stimuli, including situations involving mild shocks (Harmon, 1999).
In another study, researchers implanted human brain cells into the brains of newborn mice, and found that the mice were much more intelligent and had better memory. The brain cells used were glia cells, which play an important contribution in human intelligence. While glia do not produce electrical impulses (unlike neurons), they do produce an effect on neural activity. The researchers grafted human glial progenitor cells into the brains of the mice and observed their cognitive behavior as they became adults. The mice excelled with respect to goal-directed activities and conditioned associations.
Human glia cells, the researchers concluded, are functionally different from rodents, and play an important role in learning. In another related experiment, it was found that one could produce glial progenitor cells from human skin. This may play an important role in determining the pathological effects of abnormal glial function in humans, and may help to develop treatments for otherwise tragic neuropsychiatric disorders (Cell Press, 2013).
UT Southwestern Medical Center. (2007, May 28). ‘Smart’ Mice Teach Scientists About Learning Process, Brain Disorders. ScienceDaily. Retrieved June 29, 2014 from www.sciencedaily.com/releases/2007/05/070527200624.htm
Cell Press. (2013, March 7). Using human brain cells to make mice smarter. ScienceDaily. Retrieved June 28, 2014 from www.sciencedaily.com/releases/2013/03/130307123947.htm
Harmon, Justin. Scientists Create Smart Mouse (1999). Retrieved from: http://www.princeton.edu/pr/news/99/q3/0902-smart.htm