Rolf Sprengel, Ph.D.
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. It has for instance 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.
In order to disect the molecular mechanism responsible for LTP I was interested to generate mice which show changes in synaptic transmission. The key components of fast excitatory neurotransmission, the glutamate gated ion channels, were selected for the analysis. Different mouse lines were generated which express NMDA or AMPA receptors with altered ion permeability. Synaptic plasticity and changes in behavior were analyzed and were used to elucidate the involvement of these channels in the generation neuronal plasticity.