Brain’s background noise keeps nerve connections intact

Neurons communicate with each other via electrical signals and chemical neurotransmitters. At the junction between two neurons (synapse), an action potential causes neuron A to release a chemical neurotransmitter that passes the information to the next neuron.

This type of neuron-to-neuron communication is known as evoked neurotransmission.

Sometimes, neurotransmitter-packed droplets are released at the synapse in the absence of electrical impulses. This event is known as background noise.

This event or minis is believed to play an essential role, for example, in the development of synapses.

Brian McCabe, Director of the Laboratory of Neural Genetics and Disease and a Professor in the EPFL Brain Mind Institute, said, “If neurons in the brain were a network of computers, evoked releases would be packets of data through which the machines exchange information, whereas minis would be pings — brief electronic signals that determine if there is a connection between two computers. Minis are the pings that neurons use to say ‘I am connected.'”

Adult Drosophila neuromuscular synaptic terminals. Motor neurons (blue), synaptic boutons (red) and neurotransmitter release sites (green). © Laboratory of Neural Genetics and Disease / EPFL

To determine if minis could play a role in the mature nervous system, EPFL scientists studied a set of neurons that control movement in fruit flies. They found that the synapses started to break up into smaller fragments as the insects aged.

As nerve junctions separated, both evoked and miniature neurotransmission were hosed, and the flies showed motor problems such as a reduced ability to climb the walls of a plastic vial.

Scientists later assessed the effects of stimulating or inhibiting evoked and miniature neurotransmission. When both types of neurotransmission were hindered, synapses aged prematurely, recommending that during maturing or in neurological diseases related to old age, changes in neurotransmission happen before synapses start to crumble.

Model of NMJ synaptic structural changes in response to miniature event decline during aging. Miniature events decline during aging. In response, synaptic size decreases and fragments into smaller units. Reducing miniature events can accelerate this bouton fragmentation process in young animals while increasing these events can delay synapse fragmentation and improve motor ability in aging animals. © Laboratory of Neural Genetics and Disease / EPFL

McCabe says, “This finding upends a longstanding idea in neuroscience. The idea has long been that the structure of the synapse breaks down, and that causes a functional change in the synapse, but we found it is the other way around.”

It was also found that stimulating evoked neurotransmission alone had no impact on aging synapses, but when the frequency of minis was increased, synapses were found to be intact. It also preserved the motor ability of middle-aged flies at levels comparable to those of young flies.

McCabe said, “Motor ability declines in all aging animals, including humans, so it was a delightful surprise to see that we could change that.”

Scientists suggested, “The study could have important implications for human health: minis have been found at every type of synapse studied so far. Figuring out how a reduction in miniature neurotransmission changes the structure of synapses, and how that, in turn, affects behavior, could help to understand neurodegenerative disorders and other brain conditions better.”

Journal Reference:

1. Banerjee, S., Vernon, S., Jiao, W. et al. Miniature neurotransmission must maintain Drosophila synaptic structures during ageing. Nat Commun 12, 4399 (2021). DOI: 10.1038/s41467-021-24490-1

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