The “noise” of the brain keeps nerve connections young

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PICTURE: Adult Drosophila neuromuscular synaptic terminals. Motor neurons (blue), synaptic buttons (red) and neurotransmitter release sites (green). view After

Credit: © Laboratory of Genetics and Neuronal Diseases / EPFL

Neurons communicate through rapid electrical signals that regulate the release of neurotransmitters, the brain’s chemical messengers. Once transmitted through a neuron, the electrical signals cause the junction with another neuron, known as a synapse, to release droplets filled with neurotransmitters that transmit information to the next neuron. This type of neuron-to-neuron communication is known as evoked neurotransmission.

However, some droplets filled with neurotransmitters are released at the synapse even in the absence of electrical impulses. These miniature – or mini – output events have long been considered “background noise,” says Brian McCabe, director of the Laboratory of Genetics and Neuronal Diseases and professor at the EPFL Brain Mind Institute.

But several studies have suggested that minis have one function – and one important function. In 2014, for example, McCabe and his team showed that minis are important for synapse development. If the neurons in the brain were a network of computers, the evoked releases would be packets of data through which machines exchange information, while the minis would be pings – brief electronic signals that determine whether there is a connection between two computers, explains McCabe. “The minis are the pings that neurons use to say ‘I’m connected.'”

To assess whether minis might play a role in the mature nervous system, Soumya Banerjee, postdoctoral fellow in McCabe’s group, and her colleagues set out to study a set of neurons that control movement in fruit flies. As the insects got older, their synapses began to shatter into smaller fragments, the researchers found. (A similar process occurs in aging mammals, including humans.) As the nerve junctions deteriorated, the evoked and miniature neurotransmission was attenuated, and the flies showed motor problems such as a reduced ability to climb the walls of a plastic bottle.

Next, the team evaluated the effects of stimulating or inhibiting evoked and miniature neurotransmission. When both types of neurotransmission were blocked, synapses aged prematurely, suggesting that during aging or in neurological diseases associated with old age, changes in neurotransmission occur before synapses begin to collapse. . This discovery, says McCabe, turns a long-held idea in neuroscience upside down. “The idea has long been that the structure of the synapse collapses, causing a functional change in the synapse, but we found it to be the other way around,” he says.

Stimulation of evoked neurotransmission had no effect on aging synapses, the researchers said. However, increasing the frequency of the minis kept the synapses intact and kept the motor capacity of middle-aged flies at levels comparable to those of young flies. “Motor ability declines in all aging animals, including humans, so it was a pleasant surprise that we could change that,” says McCabe.

The conclusions, published in Nature Communication, could have important implications for human health: minis have been found in all types of synapses studied so far, and miniature neurotransmission defects have been linked to a range of neurodevelopmental disorders in children. Understanding how a reduction in miniature neurotransmission alters synapse structure, and how this in turn affects behavior, could help better understand neurodegenerative disorders and other brain conditions.

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