Strong Collaboration Leads to Innovation

April 10, 2020

In order to seamlessly manage the torrent of information around us, our brains need a lot of energy. This is particularly true when it comes to our ability to hear—we must distinguish pitch, intensity, and directionality and then respond almost instantaneously. To do so, sounds are transformed into electrical and chemical signals that are relayed throughout the brain. Mitochondria, classically known as “the powerhouse of the cell,” supply the energy required for the transfer of these signals from one neuron to the next.

Scientists from the Max Planck Florida Institute for Neuroscience’s (MPFI) Electron Microscopy Core joined the Young Lab from the University of Iowa to study the relationship between the number and location of mitochondria in the connection sites in the auditory system. The collaboration built on a long-standing scientific exchange as Samuel Young is an MPFI alum and former MPFI research group leader.

Due to their small size, the features of mitochondria and where they are located within the synaptic connections are often difficult to analyze using conventional methods and require 3D electron microscopy to fully reveal their intricate structural details. Therefore, to study the mitochondria within the auditory system, the scientists of Young Lab designed a special “label” to visualize small parts of the mitochondria with a 3D imaging process. Meanwhile, the team at the MPFI’s Electron Microscopy Core used two strategies to generate 3-dimensional images sets and detect the labeled mitochondria. The first employs Serial Block-Face Scanning Electron Microscopy (SBF-SEM) to create a large stack of images that can be reconstructed into a 3D model of the synaptic connections. The second strategy used Automated Tape-collecting Ultra-Microtome serial section Scanning Electron Microscopy (ATUM-ssSEM), to produce higher resolution images that show greater detail on sub-synaptic structures like mitochondria.

These electron microscopy techniques work more or less like a salami-slicing machine. Take a tasty peppercorn-spiked salami from Italy. If you want to study the precise the position and shape of each peppercorn (aka mitochondria) in the sausage, you need to cut the salami in very thin slices, then you can inspect the individual slices for peppercorns and take a picture, and if you put all the pictures (or slices) back one over the other together you can ‘reconstruct’ the entire salami again and visualize it in 3D.

Using the SBF-SEM strategy, both MPFI and UI scientists saw for the first time the detailed features of the mitochondria in the synaptic connections of the auditory system. The mitochondria within the mature connections were significantly larger than those of the immature connections. The data strongly implies that higher energy demands of hearing require larger mitochondria. To better understand and address a number of neurological disorders, we need a better understanding of the molecular mechanisms that regulate neuronal communication.

The strategies developed for this project blends genetic tools and advanced electron microscopy techniques in a way that will have far-reaching applications for studying other processing pathways or brain regions. The possibility of analyzing any sub-cellular structures with such high resolution naturally prompts another stream of potential studies. It is vital to recognize, however, that the development of these groundbreaking strategies was only possible due to the combination of individual expertise available in the Young Lab and the MPFI Electron Microscope Core. Their collaborative efforts allowed the development of truly innovative “tools” to help us better understand how our hearing really works. Their partnership remains strong, and it is only a matter of time before this team will produce more exciting new results.