April 11, 2011

More Young Neurons Equals Better Brain Function

Microscope image shows bright green splotches near thick orange lines. Newborn neurons (light green blotches near orange areas) are visible in part of the hippocampus of an adult mouse.Amar Sahay, Ph.D., Columbia University.

Scientists improved the cognitive ability of adult mice by boosting the survival of newborn neurons in the brain’s memory hub. Enhancing the survival of these cells, when combined with exercise, produced antidepressant effects as well. The findings may open up new avenues for treating cognitive, mood and anxiety disorders.

Humans and many other animals rely on an important cognitive ability, known as pattern separation, to distinguish between different situations that occur in similar contexts. When this cognitive ability breaks down, a person may misread cues in the environment and perceive ordinary situations as threatening. This can happen as we age, and may also be involved in anxiety conditions such as post-traumatic stress disorder.

Previous research had shown that blocking the birth of new neurons in a part of the hippocampus, the brain’s memory center, decreased pattern separation ability. Until now, however, scientists had found it difficult to selectively increase the number of young neurons in an adult animal to test whether the opposite held true.

Enter Drs. Rene Hen and Amar Sahay of Columbia University. Hen’s previous work had shown that the effects of current antidepressant medications depended on the birth of new neurons, or neurogenesis, in the memory regions of the brain. Other recent studies found that exercise can increase neurogenesis and produce antidepressant effects.

This evidence led Hen and Sahay’s research team to try to clarify the role of newborn neurons in pattern separation, depression and anxiety. Their work was funded by NIH’s National Institute of Mental Health (NIMH), and the findings were published online on April 3, 2011, in the journal Nature.

To enhance the survival of newborn neurons in the brain, the team bred mice whose neural stem cells lacked a gene that causes programmed cell death. Compared to mice that still had the gene, these mice were better at distinguishing between a chamber where they had previously received a mild foot shock and a similar-looking chamber that was safe. This showed that more neurons led to greater pattern separation ability.

However, these mice didn’t show antidepressant-like behavior, such as greater exploration in anxiety-producing situations, until they had engaged in exercise. The exercise requirement suggests that while new neurons can help improve pattern separation on their own, they need to work in tandem with other factors to cause antidepressant effects.

“Our study demonstrates that the stimulation of adult neurogenesis is sufficient to improve pattern recognition behavior but, while necessary, not sufficient to lift depression-like behavior,” Hen says.

By distinguishing the effects of neurogenesis on cognition from those on mood, this study will help guide future strategies for treating cognitive decline and conditions like depression, post-traumatic stress disorder and panic disorder.

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