Researchers from DZNE have, for the first time, observed changes in a key part of neurons known as the "axon initial segment" within living mouse brains during learning. The study, led by neuroscientist Jan Gründemann and published in "Nature Neuroscience," involved collaboration with experts from Switzerland, Italy, and Austria.
The axon initial segment is responsible for generating electrical impulses in neurons. Previously, its changes had only been documented in cell cultures or brain samples. According to Gründemann, "The axon initial segment determines whether a nerve impulse is generated or not. Thanks to specialized microscopy methods, two members of our team, Chloé Benoit and Dan Ganea, were able to monitor the size of these segments in the living brain during learning – that's a first. Until now, axon initial segments were mostly measured in cell cultures or tissue samples. We have now tracked them in the brain over several days in the context of learning."
In their experiments with mice, researchers found that as animals learned new behaviors through training sessions, the length of axon initial segments changed—some became longer while others shrank. Gründemann explained: "We found that the axon initial segments of the observed neurons changed length; they got longer or shrunk. The length of the axon initial segment determines the excitability of a neuron. Cells with a long initial segment generate stronger pulses than those with a short segment. This mechanism can therefore regulate brain activity. We do not yet know why some segments became longer and others shorter. This is presumably a crucial control lever to optimally adjust neuronal activity."
The study focused on an area of the cerebral cortex linked to learning processes but suggests this mechanism could be widespread across different brain regions. Gründemann noted: "Signals get transmitted from one neuron to another via synapses, but the axon initial segment decides whether a neuron will fire and how strong its output will be. So, in a sense, this is a master switch. Both synapses and axon initial segments influence signal transmission between neurons. Both are sites of neuroplasticity. And our study shows that both can be relevant for memory formation." He added: "Although we have only studied a specific area of the brain, we assume that, similar to synaptic plasticity, dynamic changes of the axon initial segment are a general principle associated with learning. We are planning to examine this phenomenon in other brain regions, particularly with regard to neurodegenerative diseases."
Looking ahead, researchers aim to explore how these findings relate to Alzheimer's disease—a condition where communication between neurons deteriorates due to protein deposits typical of Alzheimer's pathology. Gründemann stated: "In Alzheimer's disease, signal transmission between neurons is impaired. That is why we are interested, for example, in how the protein deposits typical of Alzheimer's affect the function of the initial segments. Such topics can be studied in mice that exhibit disease traits similar to those of Alzheimer's. This could help improve our understanding of the disease process and potentially identify entry points for future therapies."
