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Subject: NIH RESEARCHERS DISCOVER HOW BRAIN CELLS CHANGE THEIR TUNE

U.S. Department of Health and Human Services NATIONAL INSTITUTES OF HEALTH
NIH News National Institute of Neurological Disorders and Stroke
(NINDS)<http://www.ninds.nih.gov/>
For Immediate Release: Thursday, July 25, 2013

CONTACT: Christopher Thomas, 301-496-5751,
<e-mail:[log in to unmask]>

NIH RESEARCHERS DISCOVER HOW BRAIN CELLS CHANGE THEIR TUNE Study may advance
fundamental understanding of how brain cells communicate

Brain cells talk to each other in a variety of tones. Sometimes they speak
loudly but other times struggle to be heard.  For many years scientists have
asked why and how brain cells change tones so frequently.  Today National
Institutes of Health researchers showed that brief bursts of chemical energy
coming from rapidly moving power plants, called mitochondria, may tune brain
cell communication.

"We are very excited about the findings," said Zu-Hang Sheng, Ph.D., a
senior principal investigator and the chief of the Synaptic Functions
Section at the NIH's National Institute of Neurological Disorders and Stroke
(NINDS).  "We may have answered a long-standing, fundamental question about
how brain cells communicate with each other in a variety of voice tones." 

The network of nerve cells throughout the body typically controls thoughts,
movements and senses by sending thousands of neurotransmitters, or brain
chemicals, at communication points made between the cells called synapses.
Neurotransmitters are sent from tiny protrusions found on nerve cells,
called presynaptic boutons.  Boutons are aligned, like beads on a string, on
long, thin structures called axons.  They help control the strength of the
signals sent by regulating the amount and manner that nerve cells release
transmitters.

Mitochondria are known as the cell's power plant because they use oxygen to
convert many of the chemicals cells use as food into adenosine triphosphate
(ATP), the main energy that powers cells.  This energy is essential for
nerve cell survival and communication.  Previous studies showed that
mitochondria can rapidly move along axons, dancing from one bouton to
another.

In this study, published in Cell Reports, Dr. Sheng and his colleagues show
that these moving power plants may control the strength of the signals sent
from boutons.

"This is the first demonstration that links the movement of mitochondria
along axons to a wide variety of nerve cell signals sent during synaptic
transmission," said Dr. Sheng. 

The researchers used advanced microscopic techniques to watch mitochondria
move among boutons while they released neurotransmitters.  They found that
boutons sent consistent signals when mitochondria were nearby.  

"It's as if the presence of mitochondria causes a bouton to talk in a
monotone voice," said Tao Sun, Ph.D., a researcher in Dr. Sheng's laboratory
and the first author of the study.

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.

NINDS <http://www.ninds.nih.gov> is the nation's leading funder of research
on the brain and nervous system. The NINDS mission is to reduce the burden
of neurological disease - a burden borne by every age group, by every
segment of society, by people all over the world.

About the National Institutes of Health (NIH): NIH, the nation's medical
research agency, includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. NIH is the primary federal
agency conducting and supporting basic, clinical, and translational medical
research, and is investigating the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit <www.nih.gov>.

NIH...Turning Discovery into Health -- Registered, U.S. Patent and Trademark
Office
-----------
The htm version of this news release contains an image of mitochondria
interacting with nerve cells
<http://www.ninds.nih.gov/img/dancing_mitochondria.jpg>.
CAPTION:
Mitochondria Take to the Dance Floor - NIH researchers used advanced
microscopic techniques to watch mitochondria dance around and tune nerve
cell voices.  This kymograph describes their dynamic steps.  Courtesy of the
Sheng lab, NINDS, Bethesda, Md.

The htm version of this release contains a video of Nerve Cell Power Plant
Dancing at <http://youtu.be/qbm5jXCL3ZA>.

REFERENCES:
Sun et al. "Motile Axonal Mitochondria Contribute to the Variability of
Presynaptic Strength," Cell Reports, July 25, 2013. DOI:
10.1016/j.celrep.2013.06.040  

This study was funded by the NINDS' Division of Intramural Research.  For
more information, please visit: 
<http://intra.ninds.nih.gov/>

###

This NIH News Release is available online at:
<http://www.nih.gov/news/health/jul2013/ninds-25a.htm>.

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