How Brain Cells Change Their Tune, Discovered

The signal strength surprisingly fluctuated when mitochondria moved away from boutons. 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.

Potential Technique Developed To Prevent Inherited Mitochondrial Diseases
National Institutes of Health funded researchers have developed an experimental technique with the potential to prevent a class of hereditary disorders passed on from mother to child.

"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.

New Technique Could Give Out Quick and Easy Diagnosis for Mitochondrial Disorders
An innovative clinical diagnostic test for the early identification of a wide range of mitochondrial disorders is described in research published in BioMed Central's open access journal

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."

Master Network of Central Signaling Response Found in Mitochondrial Energy Diseases
A master network of signaling molecules has been identified by researchers that acts like a fuse box to regulate the cellular effects of defective energy flow in mitochondrial respiratory chain diseases—a diverse set of difficult-to-treat genetic-based energy disorders.

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.

Source-Eurekalert