A longstanding question in brain research is how information is processed in the brain. Neuroscientists at the Charité -- Universitätsmedizin Berlin, Cluster of Excellence NeuroCure and University of Newcastle have made a contribution towards answering this question. In a new study, they have shown that signals are generated not only in the cell body of nerve cells, but also in their output extension, the axon. A specific filter cell regulates signal propagation.

These findings have now been published in the journal Science.

Until now it has been assumed that information flow in nerve cells proceeds along a "one-way street." Electrical impulses are initiated at the cell body and propagate along the axon to the next neuron, where they are received by extensions, the dendrites, acting as antennae. However, the team around Charité researchers Tengis Gloveli and Tamar Dugladze has demonstrated that this model needs to be revised. They discovered that signals can also be initiated in axons, i.e. outside the cell body. This happens during highly synchronous neuronal activity as, for example, in a state of heightened attention. Moreover, these axonally generated signals flow bidirectionally and represent a new principle of information processing: on the one hand, impulses propagate from their origin towards other nerve cells; on the other hand, the signals also backpropagate towards the cell body, i.e. in the "wrong direction" down the one-way street. A potential problem is that backpropagating signals could lead to excessive cell activation.

However, the researchers found that backpropagating signals do not reach the cell body under normal conditions. The reason for this, the scientists discovered, is a natural filter that prevents these signals from passing. "Axo-axonic cells, an inhibitory cell type, regulate signal propagation and thus occupy an outstanding strategic position," explains Tamar Dugladze. Through the filter function, these cells allow signals initiated at the cell body to pass, but suppress backpropagating impulses generated in the axon. By this means, excessive activation of the cell body is prevented. In experiments, the scientists could show that when this filter function is deactivated, backpropagating signals are allowed to pass, resulting in higher cell activation.

These filter cells can become damaged in various neurological diseases. The consequent misregulation of signal flow, in turn, has fatal effects on information processing in the brain. "Results of this study shed new light on the central question of how signals are processed in the brain. In addition, these findings could help us better understand the development and progress of neuronal diseases such as epilepsy, which involves excessive hypersynchronous activity of large sets of neurons. This knowledge could open up new therapeutic approaches," says Tengis Gloveli. The neuroscientists will therefore focus their future research on both basic understanding of the mechanisms of signal flow in the nervous system, and the relevance of these mechanisms in the genesis of epilepsy.