Nav: Home

Uncovering the presynaptic distribution and profile of mitochondria

October 09, 2019

The ability to hear relies on neurons to constantly transmit information at very rapid timescales. This rapid rate of information transmission results in intense energetic demands. Within our cells, microscopic power plants called mitochondria provide the main source of energy keeping our bodies moving. While mitochondria serve an essential function throughout the body, within the brain they play an especially crucial role; providing the tremendous amount of energy needed to facilitate synaptic transmission (the transfer of information between neurons).

In the auditory system there is a large presynaptic terminal called calyx of Held that is critical for binaural sound processing. Prior to the onset of hearing, immature calyx synapses, do not release neurotransmitter at very fast rates. But once mature, they reliably and rapidly release neurotransmitter to encode auditory information., However, how mitochondria support the energy-demanding activity of the mature synapse remained unknown.

In a recent study published in the Journal of Neuroscience, scientists from the MPFI and the University of Iowa CCOM have provided unprecedented insight into the presynaptic distribution and profile of mitochondria in the developing and mature calyx of Held.

"My lab investigates how synapses enable neural circuits transmit a wide variety of information. In particular we are very interested in understanding the synaptic mechanisms that enable fast auditory signaling required for accurate identification and perception of sound information and their contribution to auditory deficits ," explains Samuel Young Jr., Ph.D., former Research Group Leader at MPFI and now Associate Professor in the Department of Anatomy and Cell Biology at the University of Iowa CCOM. "While we understand some of the general principles of how the calyx enables proper sound processing , many are still unknown. Therefore, we wanted to understand if there were mitochondrial changes at the subsynaptic levels. To answer our question, we needed the expertise of the EM core at MPFI. What started as a fledgling idea and a simple conversation and, turned into a fruitful collaborative effort."

Due to their relatively small size, mitochondrial volume and distributions are often difficult to analyze using conventional methods and require 3D- electron microscopy to fully reveal their intricate structural details. To accomplish this the Young Lab created a helper-dependent adenoviral vector with the mitochondria-targeting peroxidase, mito-APEX2 and expressed it at the mouse calyx of Held. In addition to that, the MPFI EM team developed protocols to detect APEX2-labeled mitochondria by 3D- electron microscopy to carry out extensive analysis of the presynaptic mitochondria volume and abundance.

"Our biggest challenge was to develop protocols and workflows that would allow us to image mitochondria within the calyx in fine detail using the advanced 3D- EM technologies," describes Connon Thomas, EM assistant at MPFI and first author of the publication. "After extensive optimization, we devised two strategies; the first used serial block-face scanning electron microscopy or SBF-SEM for short, which is a type of specialized EM that allows us to generate a large-scale set of 3D images in order to reconstruct and analyze mitochondria within the terminals. The second strategy used Automated Tape-collecting Ultra-Microtome serial section scanning electron microscopy (ATUM-ssSEM), which is a technique that produces higher resolution images which makes it easier to analyze fine sub-synaptic structures."

3D reconstructions of images taken with SBF-SEM revealed that mitochondrial volumes within the mature calyx and its surrounding axon were significantly higher than those found in its immature counterpart. It also seemed that mitochondria are selectively enriched within the mature calyx, containing higher volumes than the surrounding axon. This data affirms the idea that during development increased mitochondrial volumes support the higher energy demands of a more active mature calyx.

Using genetic tools developed by Young Lab and innovative new protocols developed by MPFI's EM Core, their combined expertise has generated novel approaches with broad applications in neuroscience research. "The strong collaboration between our EM Core and the Young Lab was essential for the success of this work," notes Naomi Kamasawa, Ph.D., Head of EM Core. Our collaborations will continue and will undoubted bring exciting new developments."

"The new protocols and applications developed for this work will have wide application for studying different circuits or different brain regions with combining genetic manipulation and electron microscopy," explained Young.
-end-


Max Planck Florida Institute for Neuroscience

Related Mitochondria Articles:

Unexpected insights into the dynamic structure of mitochondria
As power plants and energy stores, mitochondria are essential components of almost all cells in plants, fungi and animals.
Mitochondria are the 'canary in the coal mine' for cellular stress
Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery.
Master regulator in mitochondria is critical for muscle function and repair
New study identifies how loss of mitochondrial protein MICU1 disrupts calcium balance and causes muscle atrophy and weakness.
Oxygen deficiency rewires mitochondria
Researchers slow the growth of pancreatic tumor cells.
Self-cannibalizing mitochondria may set the stage for ALS development
Northwestern Medicine scientists have discovered a new phenomenon in the brain that could explain the development of early stages of neurodegeneration that is seen in diseases such as ALS, which affects voluntary muscle movement such as walking and talking.  The discovery was so novel, the scientists needed to coin a new term to describe it: mitoautophagy, a collection of self-destructive mitochondria in diseased upper motor neurons of the brain that begin to disintegrate from within at a very early age.
Uncovering the presynaptic distribution and profile of mitochondria
In a recent study published in the Journal of Neuroscience, scientists from the MPFI and the University of Iowa CCOM have provided unprecedented insight into the presynaptic distribution and profile of mitochondria in the developing and mature calyx of Held.
Temple researchers identify new target regulating mitochondria during stress
Like an emergency response team that is called into action to save lives, stress response proteins in the heart are activated during a heart attack to help prevent cell death.
Runaway mitochondria cause telomere damage in cells
Targeted damage to mitochondria produces a 'Chernobyl effect' inside cells, pelting the nucleus with harmful reactive oxygen species and causing chromosomal damage.
Interplay between mitochondria and nucleus may have implications for new treatment
Mitochondria, the 'batteries' that produce our energy, interact with the cell's nucleus in subtle ways previously unseen in humans, according to research published today in the journal Science.
Dissolving protein traffic jam at the entrance of mitochondria
Researchers from Freiburg discovered a novel mechanism that ensures obstacle-free protein traffic into the powerhouse of the cell.
More Mitochondria News and Mitochondria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.