Experiments Identify Two Mechanisms That Can Impair Learning
> 2/1/2008 3:07:07 PM

The ability to remember mistakes and learn quickly is crucial for survival. Unfortunately, our memory and learning functions can be compromised by a number of disorders, as well as by simple aging. Until now, many attempts to correct such breakdowns have been speculative because the exact nature of the disruption was a mystery. Two new studies in the journals Nature and Science further our understanding of a precise way that learning can be disrupted.

The Nature study, run by Dr. Chun-Li Zhang, found one reason why short term memory and learning usually degrade with age. Dr. Zhang suspected that it was the loss of neural stem cells that was causing the deterioration. To test this, she evaluated the performance of mice on a variety of learning tasks. One group of mice was given tamoxifen, an estrogen inhibitor used to treat breast cancer that also affects grey matter - it reduced the number of neural stem cells in the hippocampus of these mice by 80% in eight days. This group was still able to learn, but they suffered significant impairments that became most clear on long and difficult tasks. For example, while both groups adequately learned to associate a noise with a shock, the tamoxifen group took more than twice as many days on average to learn to navigate a complex water maze. This implies that neural stem cells are not the only mechanism for learning, but that they accelerate the process immensely. Considering that only a few years ago the prevailing wisdom insisted that no new cells grow in the adult brain, this finding on the importance of new neurons for learning is groundbreaking.

The Science study is equally innovative because it employed, for the first time, a technique that genetically shuts down a specific neural circuit. The technique, called doxycycline-inhibited circuit exocytosis-knockdown, or DICE-K, was used on mice to discover what would happen if one of the two major information pathways in the hippocampus are blocked. There are two pathways in the hippocampus, the intricate tri-synaptic pathway and the more bare-bones monosynaptic pathway. When the tri-synaptic pathway was blocked, mice were still able to learn but were much slower with complex tasks.

Both of these studies highlight the fact that the brain is incredibly versatile and has multiple ways to perform many tasks. If one of the systems breaks down, the others can often pick up some of the slack. Without understanding each system, all learning breakdowns might look the same because of similar symptoms. However, now that we know that neural stem cells and the tri-synaptic pathway are discrete vulnerabilities, we can target those precise areas for treatment.

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