Discussion about learning processes reopens

June 11, 1999

Molecular component discovered for so-called long-term potentiation (LTP) of neurons/Surprising result: Its elimination does not lead to loss of learning capacity

One of the most fascinating problems of modern biology concerns the molecular mechanisms which underlie the acquisition, computation and storage of information in the human brain. It has been a long-standing assumption that both the number of nerve cells and their connections in the human brain are immutable. However, over the past decades a growing body of evidence revealed that even the adult brain is able to reorganize and optimize its microstructure and internal connections. For instance, it has been possible to optimize information transfer between communicating nerve cells by short intensive electrical stimuli and to measure this improvement as an increased response by the neuron, which lasts for several hours. Henceforth, this test, termed long-term potentiation (LTP) in scientific textbooks, has been used as a measure for the capability of nerve cells to adapt to environmental influences which is the equivalent of learning.

Despite intensive investigations and countless publications, neither the molecular mechanisms nor the role of LTP in learning processes could be delineated. Now, with the studies of scientists at the Max Planck Institute for Medical Research in Heidelberg, which were performed in collaboration with colleagues from Oslo, Freiburg and Basel, the discussion about a participation of LTP in memory formation is gaining new momentum. On the one hand, the team achieved a breakthrough with the identification of a key molecule for the formation of LTP: it is a receptor channel for the excitatory neurotransmitter glutamate. Dr. Daniel Zamanillo succeeded in knocking out a gene for the receptor channel and thus prevented the occurrence of LTP in genetically manipulated mice without affecting neuronal transmission and cell to cell communication. With the studies of the scientists from Heidelberg as well as parallel studies by Roberto Malinow (also Science 11 June 1999) and by Robert Malenka/Roger Nicoll (Nature Neuroscience Vol. 2 1999), published at the same time, the essential steps of the mechanisms for LTP appear to be solved. There still remains, however, one unresolved and very controversial issue: To what extent does long-term potentiation participate in learning and memory acquisition? Contrary to their expectations, the scientists from Heidelberg could not demonstrate abnormal learning behaviour in the mutant mice. Rather, the mice lacking LTP were, like normal mice, capable of accurately finding a submerged, invisible platform in a pool of murky water ("water maze") and to swim there immediately when placed in the water.

Further research is needed to unambiguously solve the correlation between LTP and learning - according to the Max Planck scientists. Certainly the mouse models developed at the Max Planck Institute for Medical Research will play an important role in this endeavour.


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