NIH researchers discover how brain cells change their tune

Surprisingly, when the mitochondria were missing or moving away from boutons, the signal strength fluctuated. The results suggested that the presence of stationary power plants at synapses controls the stability of the nerve signal strength.

To test this idea further, the researchers manipulated mitochondrial movement in axons by changing levels of syntaphilin, a protein that helps anchor mitochondria to the nerve cell's skeleton found inside axons. Removal of syntaphilin resulted in faster moving mitochondria and electrical recordings from these neurons showed that the signals they sent fluctuated greatly. Conversely, elevating syntaphilin levels in nerve cells arrested mitochondrial movement and resulted in boutons that spoke in monotones by sending signals with the same strength.

"It's known that about one third of all mitochondria in axons move. Our results show that brain cell communication is tightly controlled by highly dynamic events occurring at numerous tiny cell-to-cell connection points," said Dr. Sheng.

In separate experiments the researchers watched ATP energy levels in these tiny boutons as they sent nerve messages.

"The levels fluctuated more in boutons that did not have mitochondria nearby," said Dr. Sun.

The researchers also found that blocking ATP production in mitochondria with the drug oligomycin reduced the size of the signals boutons sent even if a mitochondrial power plant was nearby.

"Our results suggest that local ATP production by nearby mitochondria is critical for consistent neurotransmitter release," said Dr. Sheng. "It appears that variability in synaptic transmission is controlled by rapidly moving mitochondria which provide brief bursts of energy to the boutons they pass through."

Problems with mitochondrial energy production and movement throughout nerve cells have been implicated in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other major neurodegenerative disorders. Dr. Sheng thinks these results will ultimately help scientists understand how these problems can lead to disorders in brain cell communication.

"Our findings reveal the cellular mechanisms that tune brain communication by regulating mitochondrial mobility, thus advancing our understanding of human neurological disorders," said Dr. Sheng.

Here is a video of mitochondrial power plants (red) passing by synaptic boutons (green) as they move through a nerve cell axon. The Sheng lab showed that their movement helps control the voice tone nerve cells use to communicate with each other.

(Photo Credit: Courtesy of the Sheng laboratory, NINDS, Bethesda, Md.)

NIH researchers use advanced microscopic techniques to watch mitochondria dance around and tune nerve cell voices. This kymograph describes their dynamic steps.

(Photo Credit: Courtesy of the Sheng lab, NINDS, Bethesda, Md.)

Source: NIH/National Institute of Neurological Disorders and Stroke