Yale scientists discover new technique for studying living cells, furthering knowledge of diseases like Parkinson's

November 10, 1999

Yale researchers have developed a new method for recording the electrical activities within living cells, which could lead to better treatment for diseases like Parkinson's, and provide clues to how learning occurs.

"This new technique offers the hope of understanding and treating degenerative neurological diseases such as Parkinson's," said Leonard Kaczmarek, M.D., professor of pharmacology at the Yale School of Medicine and the study's principal investigator.

Abnormalities of mitochondria‹tiny organelles that produce the energy to keep all cells alive‹have long been suspected in diseases like Parkinson's. Because of their small size, it has previously been impossible to record the electrical activity of mitochondria in living cells.

The new technique of mitochondrial recording will allow scientists to study parts of cells that have been inaccessible. The technique, which is detailed in the November 12 issue of Science, has already led to insights into how changes within neurons may underlie learning and memory.

Using the large nerve cells and connections of squid, the scientists devised a form of electrical recording that for the first time allowed them to observe the activity of mitochondria inside the synaptic terminal of a neuron, where information is passed from one neuron to the next.

"The effectiveness of this information transfer can change in time, and it is this kind of change that is thought to underlie learning," said Elizabeth A. Jonas, M.D., an investigator on the study who developed the technique.

Neurons are the cells of the nervous system that control behavior and moods. When a neuron receives a signal from the outside world or from another neuron, it has to have a way of "remembering" whether it has been stimulated previously. This is essential for the neuron to function properly.

"Part of this neuronal memory may occur in the mitochondria and we were surprised to find that very brief stimulation of a neuron caused electrical behavior of the mitochondria to increase 60-fold," said Jonas.

Although the neuron was stimulated for only one or two seconds, Jonas said, the mitochondria seemed to "remember" the stimulus for thirty seconds or more. This finding, coupled with earlier work, strongly suggests that the mitochondria prime the neuron to respond more effectively to new stimuli during this time.

JoAnn Buchanan, M.D., of the department of molecular and cell physiology at Stanford University, used electron microscopy to verify that the recordings were on mitochondria.
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Yale University

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