Engineered Mice Make Better Choices
A study links the creation of new neurons with improved cognitive abilities.
A study published online this week in Nature finds that mice engineered to produce more new neurons in the hippocampus—a structure involved in learning and memory—are better at discriminating between similar choices. The study adds new evidence for a link between the development of new neurons in the hippocampus and cognitive functions in the brain, and it also suggests how these neurons may affect mood disorders.
Although scientists once believed that the adult brain could only lose neurons, research over the past several years has shown not only that new neurons form regularly—a process called adult neurogenesis—but also that they contribute to brain function and are diminished in certain diseases and disorders. Drugs that can boost adult neurogenesis are currently being investigated as treatments for depression, anxiety, and neurodegenerative disease.
The exact role of new neurons, however, is still being debated. Previous studies found that blocking adult neurogenesis in the hippocampus prevented animals from discriminating between similar choices—a process called pattern separation. Amar Sahay, a postdoctoral fellow in the lab of neuroscientist René Hen at Columbia University, says that the current study sought to find out whether selectively boosting the production of new neurons in the adult hippocampus would have the opposite effect. The researchers engineered mice with a genetic switch that would turn off a gene that kills most new neurons in the adult hippocampus, thereby allowing more of these neurons to proliferate. The switch was turned on when the mice were injected with a specific drug, allowing the researchers to intervene only in adulthood.
The engineered mice performed better at a task that required them to distinguish between a chamber in which they had previously received an electric shock and a similar one with slightly different features that they’d experienced as safe. Sahay explains that pattern separation “is a mnemonic process that we use on a day-to-day basis in navigating our environments” and that it is needed to form memories and make judgments.
Previous work in Hen’s lab had shown that blocking adult neurogenesis in mice made them unresponsive to antidepressant medications. In this study, boosting new neurons did not immediately produce behaviors that suggested an antianxiety or antidepressant effect, but when the mice were allowed to run on an exercise wheel for four weeks—another known booster of new neurons—they displayed more exploratory behavior than control mice who also exercised, suggesting that environmental stimulation worked in concert with neurogenesis.
Fred Gage, a neuroscientist at the Salk Institute, says that the study “supports the emerging view that there seems to be a rather specific role for adult neurogenesis in pattern separation.” The question of how neurogenesis affects mood is less clear. Hen and Sahay propose that pattern separation may play a role in mood disorders. Sahay says that this important cognitive ability declines with age and is impaired in conditions marked by anxiety, such as panic disorders and post-traumatic stress disorder. People with anxiety, he says, “may clump previously aversive memories with new experiences that are safe.” Gage says this hypothesis, if proved true, may help explain why antidepressants help only certain patients. “It may be that there are cognitive components” of mood disorders like anxiety and depression, he says.
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