ETH Researchers Decipher Learning Processes in Mice

Protein phosphatase 1 (PP1) belongs to a group of molecules that on the basis of earlier studies has been proposed to be a controlling factor for learning and memory. The ETH researchers produced genetically modified mice in which the activity of PP1 can be reduced at will. These animals were subjected to various learning and memory tests in one of which, the mice had to learn about various objects in a box. For this, they were trained on different schedules: without any interruption during learning or with short or long interruptions. To study how well the mice could remember the objects after learning, they were placed back into the box and one of the objects had been replaced with a novel object. If the animals explored the novel object significantly longer than the others, this was an indication that the mice remembered the familiar objects.

Protein Phosphatase 1 Makes Learning More Difficult

The tests showed that the mice with reduced PP1 and with short interruptions in the learning process achieved optimal performance that could be reached by control animals only with long interruptions. Isabelle Mansuy’s interpretation of these results is that “PP1 represents a necessary controlling factor, that is required to avoid saturation of the brain. Because the capacity of the brain is limited, it needs an active protective system”.

In order to determine whether PP1 has a general effect in learning, the research group carried out another set of experiments using a test that challenges spatial orientation. In a tub of water, the mice had to find a platform located just below the surface of the water which was made opaque. The mice with reduced PP1 needed fewer training trials to learn the platform position than the control animals.

Promoting Forgetting

Then the mice’s memory was tested. Two weeks after training the mice with normal PP1 function found the platform less easily than immediately after training. But those whose PP1 function was suppressed remembered its position surprisingly well and up to eight weeks after learning. This speaks for the fact that PP1 not only makes learning more difficult, but it also actively promotes forgetting. This effect appears to be prominent in aged individuals as those with less PP1 had improved performance. The data suggest that the suppression of PP1 may protect against memory decline. “The tests with the aged mice show that cognitive abilities may be rescued”, comments Isabelle Mansuy. This is especially interesting since it is known that aged mice have more PP1. The findings therefore indicate that learning difficulties and decline of memory in old age are not necessarily unavoidable, irreversible processes.