HMN 2026: How Modifiable neurons lose their function with age

While probing the escape reflex in the fruit fly Drosophila, researchers at Johannes Gutenberg-University Mainz (JGU) and the National and Kapodistrian University of Athens, Greece, found that the synapses of one of the participating neurons can learn. This plasticity likely leads to the synapse not being functional anymore at old age, thus abolishing the escape reflex.

“Our results—together with data from the mammalian brain uncovered by other research groups—suggest that the price for functional circuit plasticity could be vulnerability during aging,” stated Professor Carsten Duch of the Institute of Developmental Biology and Neurobiology of JGU. These findings were recently published in PLOS Biology.

Young and middle-aged flies escape a predator-like stimulus with a jump followed by flight. Specific neurons in the fly eye, visual interneurons, are synaptically connected to the giant fiber, a large conductor of neural impulses, which is present once per brain hemisphere. There, information is transformed into signals that are conducted to the ventral nerve cord where the motoneurons are located.

Motoneurons are neurons that directly control muscles. The giant fiber first activates the jump motoneuron and then, slightly delayed, the wing motoneurons so that the animal escapes by first jumping and then flying away.

However, a repetitive stimulus, like a swaying leaf, leads to the escape response becoming smaller until finally seizing completely—the fly learns that no reaction is needed to this particular stimulus until a new threatening stimulus appears. This known mechanism was investigated further.

“By manipulating the so-called LC4 visual interneurons specifically, we showed that the habituation to repetitive stimuli is due to the LC4 visual interneurons’ ability to learn rather than any other part of the escape pathway. This means that the synapse between the LC4 neurons and the giant fiber can learn,” Duch explained.

To be precise, the researchers removed a particular potassium channel that is known to be essential for habituation of the escape response in different neurons that participate in the escape response. Which neurons specifically were responsible for habituation of the escape response was not known. Upon removal of specific potassium channels in LC4 neurons, the fly did not habituate anymore. However, removal of these potassium channels in other neurons had no effect—the fly still habituated. Thus, the location for habituation appears to be in the connection between LC4 neurons and the giant fiber.

The escape reflex declines with age

In addition, the escape response declines with age, as the team discovered. “The ability of the synapse to learn comes at the price of losing its function at old age so that the escape reflex fails,” Duch said. Synapses that do not learn, like for example the synapses that connect the motoneurons with their target muscles, work reliably also at old age. This means the fly could still jump but the signal to do so never comes. “The price for plasticity is vulnerability,” said Duch.

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